Path: weeds!utopia!hacktic!sun4nl!mcsun!!!!f1sami
From: (Samu Mielonen)
Newsgroups: alt.drugs
Subject: Re: Smart Drugs: Anyone here take them?
Date: 31 Aug 1993 11:06:32 +0300
References: <> <>
Organization: University of Tampere, Finland
Lines: 2171

"Brooke Paul ( wrote:

": 	Picratam doesn't appear to work.  Several studies have shown that
": it doesn't cross the blood-brain barrier. () writes:

"	If piracetam does not work, then why has it gained such a reputation
"as a nootropic?  I have never tried it, nor do I know anybody that has.  Has
"it all just been dumb rumors?  Are there any nootropic drugs out there that
"DO work?  What about vassopressin inhalers?

I'm not sure whether these have relevance to anyone, but here goes:

                               SMART DRUGS

There is a class of drugs known as nootropics which improve the cognitive
functions of the brain including memory retentiom, cortical vigilance,attention
span and concentration. Most physicians in the US have
no or limited knowledge of these drugs for several reasons.

1. If the drug is approved for one indication and is found to have other
uses, it is illegal under the FDA regulations for the drug company to inform
physicians of unapproved uses. It is legal for a doctor to prescribe a drug for
other than FDA approved uses and many doctors do even though they increase
their possible exposure to malpractice.

2.If the patent has expired or is close to expiration, no company can afford to
spemd 70 million and 6 years to get FDA approval for additional use when a
generic equivalent is available. Drug companies will at times sponsor studies
set up to descredit the effectiveness of such drugs particularly if they are
attempting to get approval of or working on a new drug that will have the same
effects but can be patented. The attack on Dilantin and Hydergine are good
examples.  There are several thousand studies on each showing effectiveness in
a wide range of conditions. Most are double-blind, prospective and published
in a peer-reviewed medical journal. Any single study showing little effect or
efficacy can be circulated to physicians without restriction but the studies
showing positive results for unapproved uses cannot.  Over 2000 references to
benefcial effects but most physicians are more aware of single review
discrediting its use.

3. The FDA has never approved a nootropic drug. If there is no disease
there is no need for a drug is the attitude. To gain approval of  a drug in
this country that improves memory, information processing or mental vigilance
is not possible unless it can be shown to work on a disease like Altzheimers or

4.Some of the best of these drugs are not available in this country and will
never be even unles there are massive changes in our system though they are
sold over the counter in the rest of the world. They can be legally ordered by
mail without prescription  from companies like Interlab in England.

For general articles etc the following are suggested: Pelton, Mind Food and
Smart Pills
Longevity Magazine about June of 91 had a good article on antiaging drugs
and other sources for legal mail order.

Some medical references particularly to Piracetam follow;

Wittenborn JR
Pharmacotherapy for age-related behavioral deficiencies.
J Nerv Ment Dis 1981 Mar;169(3):139-56

This review observes a distinction between drugs for treating age-
  related behavioral losses or impairments among the old and the
  psychopharmacotherapeutic drugs used in treating disturbed or
  disordered behavior in adults of various ages. The placebo-controlled
  studies confirm numerous responses to drugs designed specifically for
  treating impaired behavior in old people, and the responses of normal
  or mildly impaired subjects to some of these drugs suggest the
  possibility of prophylactic applications.


Krejci I  Dlabac A
Bar-pressing for water reward: effects of nootropic drugs and
  peptides on discrimination learning in rats.
Act Nerv Super (Praha) 1984 Jun;26(2):103-11

Rats maintained on 23-hr water deprivation were first trained to bar-
  press for continuous water reinforcement and then to discriminate
  between regularly alternating periods (24 sec) during which time a
  light signal was either on and each response was reinforced or the
  light was off and bar-presses were not rewarded. The following drugs
  were injected s. c. prior to the sessions of discriminative learning:
  piracetam, 1-(4-Methyl-piperazinocarbonylmethyl)-2-
  pyrrolidone/hydrogen maleate (VUFB 13763), N alpha-glycyl-glycyl[8-
  lysine]des-9-glycinamide-vasopressin (DG-Trigly-LVP) and an analog of
  MIF, EUC-Leu-beta-Ala-NH2 (EUC, 2-oxoimidazolidine-1-carboxylic
  acid). None of the drugs influenced the total number of bar-pressing
  (sum of reinforced and non reinforced responses). Piracetam (100, VUFB 13763 (40 and EUC-Leu-beta-Ala-NH2 (1
  1) improved the performance of rats on the discrimination learning
  task, DG-Trigly-LVP slowed the rate of acquisition.

Mysliveckova-Hassmannova J  Myslivecek J  Janda F
Learning and memory under the influence of emotional stress and
  nootropic drug action.
Act Nerv Super (Praha) 1978 Dec;20(4):264-6

Morgenstern E  Stattmann A  Voigt JP
Influence of piracetam on anticonvulsant effects of antiepileptic
  drugs in mice.
Act Nerv Super (Praha) 1990 Mar;32(1):55-6

Institutional address:
     Inst. pharmacol. Forschung

Pavlik A  Benesova O  Dlohozkova N
Effects of nootropic drugs on brain cholinergic and dopaminergic
Act Nerv Super (Praha) 1987 Mar;29(1):62-5

High affinity choline uptake (HACU) in the hippocampus and striatal
  concentration of dopamine (DA) and homovanillic acid (HVA) as
  measures of the in vivo acetylcholine and DA turnover, respectively,
  were estimated in male rats, Long-Evans, following 6-day
  administration of various nootropics in clinically relevant doses:
  piracetam and its derivatives pramiracetam and oxiracetam (100
  mg/kg/day), pyritinol (50 mg/kg/day). Piracetam treatment was without
  effect on HACU, but induced significant increase of HVA in the
  striatum leaving striatal DA concentration unchanged. On the
  contrary, pyritinol, pramiracetam and oxiracetam increased HACU, but
  did not change striatal DA and HVA levels.

Wustmann C  Rudolph E  Schwipper U  Ranacher B  Fischer HD  Schmidt J
[Effect of nootropic drugs on the dopamine release and dopamine
  uptake in structures of the rat striatum]
Einfluss von Nootropika auf die Dopaminfreisetzung und
  Dopaminaufnahme in Strukturen des Rattenstriatum.
Acta Biol Med Ger 1982;41(6):575-9  (Published in German)

Nootropics increase the overflow of dopamine from rat striatum slices
  in a concentration dependent manner, but without relation to their
  clinical effectiveness. The influence of a nootropic drugs and of
  amphetamine on the stimulus induced dopamine release points to a
  relationship between nootropic and nooanaleptic activity, on the one
  hand, and transmitter release, on the other. Dopamine re-uptake is
  not altered by nootropics like piracetam.

Gallai V  Mazzotta G  Del Gatto F  Montesi S  Mazzetti A  Dominici P
  Della Monica A
A clinical and neurophysiological trial on nootropic drugs in
  patients with mental decline.
Acta Neurol (Napoli) 1991 Feb;13(1):1-12

The different expressions of mental decline in elderly people, from
  simple senile benign forgetfulness to SDAT, can be evaluated by
  psychometric and neurophysiological tests. In the present study, the
  effects of oxiracetam, piracetam and placebo were compared in a group
  of elderly subjects. The results of the trial, structured as single
  blind, clearly showed that nootropics positively effect both clinical
  and neurophysiological performances and that oxiracetam produces a
  more pronounced effect when compared to piracetam. In fact,
  oxiracetam was found more effective in improving psychometric scales
  such as GDS (clinical performances) as well as the amplitude and the
  latency of the P300 (neurophysiological performances), which reflect
  a functional recovery of the cerebral pathways related to attention
  and memory.

Institutional address:
     Istituto di Clinica Delle Malattie Nervose e Mentali Universita di Perugia

Mondadori C  Schmutz M  Baltzer V
Potentiation of the anticonvulsant effects of antiepileptic drugs by
  "nootropics"; a potential new therapeutic approach.
Acta Neurol Scand Suppl 1984;99:131-2

Petkov VD  Belcheva S  Stoyanova V  Petkov VV
Effects of nootropic agents on the performing of active two-way
  avoidance tasks in young and old rats.
Acta Physiol Pharmacol Bulg 1990;16(3):35-42

Experiments were made on 2- and 18-month-old male rats to test the
  effects on the acquisition and retention of piracetam, meclofenoxate
  and four newly-synthesized substances with assumed nootropic action:
  pyrrolidine derivatives with code names p-F, p-P and A-T, as well as
  the derivative of para-chlorophenoxypropionic acid, with code name 4-
  Cl-alpha PA. The method of two-way active avoidance was used, with
  punishment reinforcement during 5-day training and retention tests on
  the 14th day after the beginning of training. The agents studied were
  applied orally in doses of 30 and 150 mg/kg for 3 days (2 days before
  training and on the first day of training) and then again one hour
  before the retention testing. The older rats manifested a poorer
  learning capacity than the younger ones. Piracetam produced the best
  effect both on learning and on retention. Compounds with code names p-
  F, p-P and A-T induced an increase in the number of avoidances
  compared with the controls on isolated days only, according to the
  tests for acquisition. The favourable effects observed are not in
  close dependence either on the dose applied, or on the age of the
  experimental animal. No significant effects were observed under the
  effect of meclofenoxate and of its structural analogue 4-Cl-alpha

     Institute of Physiology
     Bulgarian Academy of Sciences.

Genkova-Papasova M  Lazarova-Bakurova M
Influence of nootropic drugs on the memory-impairing effect of
  diethyldithiocarbamate and clonidine in "step down" passive avoidance
  in albino rats.
Acta Physiol Pharmacol Bulg 1988;14(4):36-41

Experiments on albino rats were carried out to study the effects of
  the nootropic drugs piracetam, aniracetam, meclofenoxate and fipexide
  on the DA-beta-hydroxylase inhibitor diethyldithiocarbamate- and the
  alpha 2-adrenoceptor agonist clonidine-impaired cognitive functions.
  The changes in memory were studied by the step down passive avoidance
  with punishment reinforcement. Diethyldithiocarbamate, injected
  intraperitoneally at a dose of 300 mg/kg and clonidine at a dose of
  0.1 mg/kg i. p. considerably impaired retention for passive
  avoidance. The administration of piracetam (600 mg/kg), aniracetam
  (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg) orally
  for 5 days prior to training completely abolished the memory-
  impairing effect of diethyldithiocarbamate and clonidine. The role of
  NAergic neurotransmitter system for the memory disturbances caused by
  diethyldithiocarbamate and clonidine as well as for the protective
  effects of the nootropic agents tested is discussed.

Institutional address:
     Institute of Physiology
     Bulgarian Academy of Sciences.

Petkov VD  Mosharrof AH  Petkov VV
Comparative studies on the effects of the nootropic drugs
  adafenoxate, meclofenoxate and piracetam, and of citicholine on
  scopolamine-impaired memory, exploratory behavior and physical
  capabilities (experiments on rats and mice).
Acta Physiol Pharmacol Bulg 1988;14(1):3-13

The effects of adafenoxate (Adf), meclofenoxate (Mf), piracetam (Pc),
  and citicholine (CCh) on scopolamine (Scop)--impaired memory and
  exploratory behavior (experiments on rats) and on physical
  capabilities (experiments on mice) were studied. In the experiments
  with scopolamine (2 mg/kg i.p.) we used the step-through passive
  avoidance method to determine the memory changes. In the case of
  single treatment with the drugs tested scopolamine was injected
  immediately after training and Adf, Mf, and CCh at doses of 20 and
  100 mg/kg and Pc at a dose of 100 mg/kg were administered immediately
  after scopolamine. In the case of multiple administration the drugs
  were applied at the same doses for 7 days before training.
  Scopolamine was injected immediately after training. Retention tests
  were given 3 and 24 hours later. All the four drugs tested prevented
  to a large extent or completely the scopolamine-induced retrograde
  amnesia. However, significant quantitative differences in the
  antiamnestic effects of the drugs tested were observed. The effects
  of the four drugs on exploratory behavior were tested in the Opto
  Varimex apparatus. After 7-day treatment with the drugs at the doses
  utilized, the behavior of experimental animals was observed for 10
  min, checking out the changes in the frequency of rearing,
  ambulation, and rotation. Only Adf at a dose of 50 mg/kg
  significantly decreased rearing and ambulation frequencies; this
  effect was considered to be an expression of accelerated habituation.
  The physical capabilities of mice were studied, using the method of
  treadmill (revolving drum activity cage) training. Before the
  experiment the mice received orally Adf, Mf, and Pc at a dose of 100
  mg/kg or were injected intraperitoneally with CCh at doses of 50 and
  100 mg/kg once daily for 7 days. The number of revolutions of the
  drum cages was counted for 4 hours. Only Pc significantly increased
  the physical capabilities of mice and much delayed the occurrence of

Institutional address:
     Institute of Physiology
     Bulgarian Academy of Sciences

Petkov VD  Getova D  Mosharrof AH
A study of nootropic drugs for anti-anxiety action.
Acta Physiol Pharmacol Bulg 1987;13(4):25-30

The effects of adafenoxate (100 mg/kg), aniracetam (50 mg/kg),
  meclofenoxate (100 mg/kg), piracetam (250 mg/kg), and standardized
  ginseng extract-G115 (100 mg/kg) applied for five days were studied
  with Vogel's conflict procedure in which thirsty naive rats were
  periodically administered shocks for licking water. The results
  showed a significant anti-anxiety effect (increases in licking) with
  adafenoxate and meclofenoxate. Piracetam significantly suppressed
  licking behaviour and this effect was evaluated as anxiogenic
  (resulting from the non-specific stimulant action of the drug).
  Adafenoxate was found to increase also the number of entries into and
  escapes from the dark compartment without punishment responding. This
  effect of adafenoxate was considered to be an expression of
  facilitated conditioned-reflex activity. A beneficial role for the
  observed anti-anxiety effects of adafenoxate and meclofenoxate in the
  nootropic action of these drugs is suggested.

Institutional address:
     Institute of Physiology
     Bulgarian Academy of Sciences

Petkov VD  Kehayov R
Individually-determined differences in the effects of psychotropic
  drugs on memory (experiments on rats).
Acta Physiol Pharmacol Bulg 1987;13(3):30-6

Using the methods for "staircase-maze" training with positive
  (alimentary) reinforcement and "steps down" passive avoidance with
  punishment (electroshock) reinforcement, we divided the experimental
  animals into three groups: "good", "intermediate", and "poor"
  learners. In the course of seven days the animals of the three groups
  were treated with five substances and were then tested for retention
  with both methods. Amphetamine at single doses of 0.1 and 0.5 mg/kg
  was injected s. c. 30 min before the retention test given on the 7th
  day after the end of training. The other four drugs were administered
  twice daily throughout the period between the end of training and
  retention testing (seven days). Adafenoxate was applied at a dose of
  10 mg/kg, piracetam at doses of 50, 150, and 300 mg/kg, and
  aniracetam at doses of 50 and 150 mg/kg--all the three drugs were
  administered orally; citicholine was injected at doses of 10 and 50
  mg/kg i. p. The effects of the substances tested significantly
  differed depending on the animal's belonging to one or another group.
  Furthermore, depending on the retention test, the drug tested and the
  dose used, we observed differences in the effects not only in the
  different groups but also in one and the same group. Not taking into
  account the individual capabilities of experimental animals to
  acquire a retention task might lead to an incorrect characterization
  of such an important property of psychotropic drugs as their effect
  on memory process.

Institutional address:
     Institute of Physiology
     Bulgarian Academy of Sciences
Giurgea CE  Greindl MG  Preat S
Nootropic drugs and aging.
Acta Psychiatr Belg 1983 Jul-Aug;83(4):349-58

Nootropics are drugs which ameliorate the functional "plasticity" of
  the central nervous system. The nootropic drug acts at the
  telencephalic level through a series of bioenergetic,
  hemorheological, microcirculatory and neurochemical mechanisms. As to
  this, recent data show a facilitation by piracetam, of the efficiency
  of the central cholinergic system.

Neumann HJ  Machinek KP  Peter U  Spitschak K  Huhn U  Hollnack W
  Umlauft K
[Stimulation of prenatal development in laboratory animals by
Stimulation der pranatalen Entwicklung bei Laboratoriumstieren durch
Arch Exp Veterinarmed 1989;43(4):593-601  (Published in German)

Described in this paper is the use of nootropics for stimulation of
  prenatal development of laboratory animals. Investigations, in that
  context, led to the discovery of so far unknown and unexpected
  properties of this group of medicaments. Foetal weight gain,
  reduction of teratogenicity, and decrease in implantation loss proved
  to be some of them.

Sansone M  Ammassari-Teule M  Oliverio A
Interaction between nootropic drugs and methamphetamine on avoidance
  acquisition but not on locomotor activity in mice.
Arch Int Pharmacodyn Ther 1985 Dec;278(2):229-35

Two nootropic drugs, oxiracetam and piracetam, were tested, alone or
  in combination with methamphetamine, on locomotor activity and
  shuttle-box avoidance acquisition in mice of the C57BL/6 strain.
  Oxiracetam (50 mg/kg/day) and piracetam (100 mg/kg/day) had no effect
  when given alone, but significantly increased avoidance responses
  when combined with methamphetamine (0.5, 1 and 2 mg/kg). On the
  contrary, the two nootropic agents did not affect locomotor
  stimulation induced by methamphetamine. The results suggest that
  nootropic drugs may interact with methamphetamine in behavioural
  tests in which learning and memory processes are involved.

Sansone M  Castellano C  Ammassari-Teule M
Improvement of avoidance acquisition by the nootropic drug oxiracetam
  in mice.
Arch Int Pharmacodyn Ther 1985 May;275(1):86-92

The nootropic drug, oxiracetam (25 or 50 mg/kg i.p.), was tested in
  two inbred strains of mice, subjected to shuttle-box avoidance
  training. The drug improved avoidance acquisition in good performers
  BALB/c mice more than in poor performers C57BL/6 mice. In both cases
  the avoidance facilitating action was evident only if training was
  preceded by a five-day pretreatment. The nootropic prototype,
  piracetam (100 mg/kg), facilitated avoidance acquisition in
  pretreated BALB/c, but not in C57BL/6 mice.

Brust P
Reversal of scopolamine-induced alterations of choline transport
  across the blood-brain barrier by the nootropics piracetam and
Arzneimittelforschung 1989 Oct;39(10):1220-2
The choline transport across the blood-brain barrier was studied in
  nine brain regions of male Wistar rats after treatment with
  scopolamine, piracetam and pramiracetam, respectively. 14-Day
  treatment with scopolamine (0.5 mg/kg/d) elicited an increase of the
  extraction and the PS-product (permeability-surface area) of choline
  which was prevented by coinjection of piracetam or pramiracetam (100
  mg/kg/d). In addition, the cerebral blood flow was increased by both
  nootropics. Differences between various brain regions were found in
  both choline transport and cerebral blood flow. It is supposed from
  the results that the choline transport is regulated by cholinergic
  innervation of the brain endothelial cells and that the nootropics
  used may act via alterations of the brain choline metabolism.

Institutional address:
     Department of Cell Biology and Regulation
     Karl Marx University
     German Democratic Republic.
Stegink AJ
The clinical use of piracetam, a new nootropic drug. The treatment of
  symptoms of senile involution.
Arzneimittelforschung 1972 Jun;22(6):975-7

Mondadori C  Ducret T  Petschke F
Blockade of the nootropic action of piracetam-like nootropics by
  adrenalectomy: an effect of dosage?
Behav Brain Res 1989 Aug 1;34(1-2):155-8

The present experiments demonstrate that the absence of any memory-
  improving action of nootropics in adrenalectomized animals cannot be
  ascribed to an effect of dosage. Doses of 1, 10, 100, 1000 and 3000
  mg/kg p.o. of piracetam, oxiracetam, aniracetam or pramiracetam are
  ineffective in adrenalectomized mice.

Institutional address:
     Pharmaceutical Research Department
     CIBA-GEIGY Limited

Ennaceur A  Cavoy A  Costa JC  Delacour J
A new one-trial test for neurobiological studies of memory in rats.
  II: Effects of piracetam and pramiracetam.
Behav Brain Res 1989 Jun 1;33(2):197-207

The effects of the nootropic drugs Piracetam (Pir) and Pramiracetam
  (Pram) were evaluated on recognition-memory of rats in a new one-
  trial test. This test is based on spontaneous exploratory activity
  and does not involve rule learning or reinforcement. Recognition is
  measured by the time spent by rats in exploring two different
  objects, one familiar (the sample), the other new. When the retention
  interval is 1 min, normal rats spend more time exploring the new
  object which demonstrates that they recognize the familiar one, but
  they do not discriminate between the two objects after a 24-h
  interval. Three doses of Pram (15, 30 and 60 mg/kg) and Pir (100, 200
  and 400 mg/kg) were administered i.p. 30 min before the acquisition
  trial. The doses of 30 mg/kg of Pram and of 400 mg/kg of Pir produced
  a significant improvement in retention when the intertrial interval
  was 24 h. This effect was not associated with a change in overall
  exploratory behavior. This study shows that the new object-
  recognition test may be a useful tool for pharmacological studies of
  memory in rats.

Institutional address:
     Laboratoire de Psychophysiologie
     Universite Paris VII
Mondadori C  Ducret T  Borkowski J
The memory-enhancing effects of the piracetam-like nootropics are
  dependent on experimental parameters.
Behav Brain Res 1989 May 1;33(1):79-82

The effects of the nootropic agent piracetam and its congeners
  oxiracetam, pramiracetam and aniracetam on the retention performance
  of mice in a passive-avoidance situation are dependent on the
  intensity of the foot-shock applied. This phenomenon is observed upon
  both pre-trial and post-trial drug administration.

Institutional address:
     Pharmaceutical Research Department
     CIBA-GEIGY Limited

Nicholson CD
Nootropics and metabolically active compounds in Alzheimer's disease.
Biochem Soc Trans 1989 Feb;17(1):83-5

[No Abstract Available]

Institutional address:
     Organon Laboratories Limited
Wustmann C  Blaschke M  Rudolph E  Fischer HD  Schmidt J
Influence of nootropic drugs on the age-dependent potassium-coupling
  of transmitter release.
Biomed Biochim Acta 1990;49(7):619-24

The potassium-induced dopamine release from rat striatum slices shows
  an age-dependent decline comparable to observations after hypoxia.
  Pretreatment of aged animals with antihypoxically active nootropic
  drugs for three weeks results in an improvement of the impaired
  transmitter release. Simultaneously the slope of the stimulus-release
  relation is increased and an age-related 50% decrease of the high
  affinity Ca(++)-ATPase activity (brain P2 fraction) is partially
  compensated. Like the antihypoxic effect, the effectiveness of
  nootropic drugs regarding age-dependent changes of neuronal functions
  probably will consist, above all, in vascular influences of the
  microcirculation, repair of phospholipids damaged by free radical
  triggered peroxidation and improvement of stimulus-release coupling.

Institutional address:
     Institute of Pharmacology and Toxicology
     Medical Academy Carl Gustav Carus

Funk KF  Schmidt J
Changes of dopamine metabolism by hypoxia and effect of nootropic
Biomed Biochim Acta 1984;43(11):1301-4

An 18 h lasting moderate hypoxia equivalent to 7000 m altitude rises
  DOPAC level in the caudate nucleus and the mesolimbic area of the rat
  to about 130%. This elevation is counteracted by a singular high dose
  of nootropics of the "energy mobilizer" type, but not by vasoactive
Schmidt J
Nootropic drugs reduce immobility in behavioural despair test in
Biomed Biochim Acta 1984;43(11):1295-9

The effect of different nootropic drugs (piracetam, pyritinol,
  meclofenoxate, methylglucamine orotate, dihydroergotoxine,
  nicergoline, vinpocetine) on the duration of immobility in the
  behavioural despair test in mice was studied. All tested nootropics
  exhibited a dose-related reduction in immobility. In connection with
  the discussed role of monoaminergic processes in the state of
  immobility our data support the possible participation of central
  monoaminergic systems in the mechanisms of action of nootropic drugs.

Dienel A  Andreas K  Schmidt J
[Effect of nootropic agents on the lowering of the spasm threshold
  after a single ethanol application]
Einfluss von Nootropika auf die Ernierdrigung der Krampfschwelle nach
  einmaliger Athanolapplikation.
Biomed Biochim Acta 1984;43(10):1179-84  (Published in German)

We used the effect of ethanol on the convulsion threshold as model of
  injuriousness to analyse the CNS protective efficacy of nootropics.
  The CD50 of picrotoxine in mice was significantly diminished in
  comparision with the controls between 5 and 6 hours after 66 mmol/kg
  ethanol administered intraperitoneally and between 7 and 8 h after
  92.4 mmol/kg. In this moment the administered ethanol was already
  eliminated; the effect is explained as a reversible consequence of
  the previous ethanol exposition. The influence of nootropics was
  examined. Piracetam (0.7 mmol/kg i.p.) as well as
  methylglucaminorotate (MGO) (0.68 mmol/kg-1 i.p.) suppressed the
  ethanol effect on the convulsibility, pyritinol (0.82 mmol/kg) was
  ineffective, and meclophenoxate (1.02 mmol/kg) by itself decreased
  the convulsions threshold.
Fischer HD  Schmidt J  Wustmann C
On some mechanisms of antihypoxic actions of nootropic drugs.
Biomed Biochim Acta 1984;43(4):541-3

The antihypoxic effect of meclofenoxate hydrochloride seen in the
  accelerated restitution of posthypoxic dopamine release inhibition
  originates in the alcoholic component of the drug. Via choline
  dimethylaminoethanol might run, like orotic acid, into a CDP-choline
  pool, the generation of which is able to be facilitated by piracetam
  which in turn increases the phosphorylation potential. All these
  nootropic drugs will in this way increase the biosynthesis of
  hypoxically vulnerable phospholipids by different mechanisms. Indeed,
  a combined treatment with piracetam, meclofenoxate hydrochloride and
  methylglucamineorotate leads to a more rapid restitution of
  posthypoxic dopamine release inhibition than the drugs are active
  when applied separately.

Fischer HD  Wustmann C  Rudolph E  Zaytsev YuV  Borodkin YuS  Schmidt J
The antihypoxic effect of ethymisole: a comparison with other
  nootropic drugs.
Biomed Biochim Acta 1989;48(10):843-7

Ethymisole reveals a potent antihypoxic effect which is produced
  probably both by an acute free radical scavenging property and a
  persisting restitutive component of action. This is seen in its
  effect on posthypoxic inhibition of dopamine release from striatum
  slices of adult rats. Though ethymisole is considered a drug which
  increases brain adaptive potency, it does not modify the stimulus-
  response relation of potassium-evoked dopamine release in an
  adaptation-like manner, as it is seen after a long-lasting piracetam

Institutional address:
     Institute of Pharmacology and Toxicology
     Medical Academy
     Carl Gustav Carus

Funk KF  Schmidt J
[Cholinergic effects of nootropics]
Zur cholinergen Wirkung von Nootropika.
Biomed Biochim Acta 1988;47(4-5):417-21  (Published in German)

With respect to the enhancing effect of nootropics on learning and
  memory, the influence of some of these drugs on the high affinity
  choline uptake has been investigated. Meclofenoxate competes with
  choline uptake in vitro because of its similar side chain; other
  nootropics are without in vitro effects. A single dose of
  pramiracetam enhances the choline uptake in cortex and hippocampus.
  Application of meclofenoxate decreases the uptake of choline. Other
  nootropics lack acute effects. Possible increases of uptake after
  repeated dosage disappear within 24 h.

Institutional address:
     Institut fur Pharmakologie und Toxikologie
     Medizinische Akademie Carl Gustav Carus
Gramatte T  Wustmann C  Schmidt J  Fischer HD
Effects of nootropic drugs on some behavioural and biochemical
  changes after early postnatal hypoxia in the rat.
Biomed Biochim Acta 1986;45(8):1075-82

Piracetam (PIR) and dimethylaminoethanol (DMAE) were tested with
  respect to their ability to prevent changes of the locomotor
  behaviour and of the dopamine release from striatum slices after an
  intermittent postnatal hypoxia in the rat (2nd-10th day of postnatal
  life). The drugs given to pregnant rats (from 12th day of gestation)
  and continued after delivery to the newborns (till 10th day of
  postnatal life) displayed antihypoxic effects. Perinatal DMAE- but
  not PIR-treatment diminishes the consequences of postnatal oxygen
  deprivation regarding the motor activity as well as the dopamine
  release of adult animals. Hypoxia-caused open field hyperactivity of
  developing rats was found to be reduced to control values in PIR-
  treated rats. Only minor effects were seen after DMAE-treatment, but
  a marked depressant own effect on the explorative activity was
Wetzel W
Effects of nootropic drugs on the sleep-waking pattern of the rat.
Biomed Biochim Acta 1985;44(7-8):1211-7

The effect of nootropic drugs on sleep-walking pattern was
  investigated in adult male Wistar rats. Continuous polygraphic sleep
  recording was made 8 h per day between 8.00 a.m. and 4.00 p.m.
  Piracetam (100 mg/kg), meclofenoxate (100 mg/kg), pyritinol (100
  mg/kg), or methylglucamine orotate (225 mg/kg) were injected
  intraperitoneally immediately before the onset of recording. The
  substance effects were compared to pre-drug and post-drug NaC1
  control days. The paradoxical sleep (PS) latency was prolonged by
  pyritinol and methylglucamine orotate. The percentage of PS was
  decreased by pyritinol and methylglucamine orotate, but increased by
  piracetam. Pyritinol and methylglucamine orotate decreased the number
  of PS episodes, whereas piracetam increased the mean duration of PS
  episodes. Meclofenoxate had no significant effects except for an
  increase in the number of very long PS episodes (5 min or more). Slow
  wave sleep and walking were affected only in the case of pyritinol.
  But also pyritinol, similar to piracetam and methylglucamine orotate,
  seems to have selective actions on PS as shown by the PS/total sleep

Dienel A  Andreas K  Schmidt J
Influence of nootropic drugs on drinking behaviour in ethanol-
  preferring mice and ethanol-induced increase of seizure
Biomed Biochim Acta 1985;44(5):767-71

The influence of several nootropic drugs (piracetam, pyritinol,
  meclofenoxat, methylglucamine orotate (MGO) and dihydroergotoxine
  (DHET) on both the ethanol preference and the enhanced seizure
  susceptibility after a single dose of ethanol was studied. Piracetam,
  MGO and DHET reduce the ethanol drinking in ethanol-preferring mice.
  The enhanced seizure susceptibility after a single dose of ethanol
  was abolished by piracetam and MGO.

Burov IuV  Robakidze TN  Kadysheva LV  Voronin AE  Shaposhnikova GI
[Study of anti-amnesic activity of amiridin in a model of amnesic
Izuchenie antiamnesticheskoi aktivnosti amiridina na modeli
  amnesticheskogo sindroma.
Biull Eksp Biol Med 1991 Jun;111(6):614-7  (Published in Russian)

The model of amnestic syndrome obtained by treatment with scopolamine
  during 20 days in rats was used to study anti-amnesic activity of
  amiridin in comparison with that of tacrine, physostigmine and
  piracetam. Multiple injection of Sc resulted in significant
  deterioration of rats, performance in passive avoidance test.
  Behavioral disorders were accompanied by such changes in lipid
  composition of brain synaptosomes which indicated a decreased
  membrane fluidity. Amiridin and tacrine as well as piracetam showed
  anti-amnesic action which in the course of treatment correlated with
  their normalizing effect on lipid content of synaptosomes. The
  diverse effect of amiridin and tacrine with respect to physostigmine
  implies that the former drugs can't be attributed to
  anticholinesterase preparations which are traditionally used in the
  treatment of Alzheimer disease.

Ostrovskaia RU  Gudasheva TA
[Detection of nootropic activity indicated by acute inhibition of
  orientation reaction]
Vyiavlenie aktivnosti nootropov po pokazateliu ostrogo ugashcheniia
  orientirovochnoi reaktsii.
Biull Eksp Biol Med 1991 May;111(5):498-500  (Published in Russian)

Exploratory locomotor activity was studied in the experiments on
  adult male mice. It was shown that routine nootropic drugs as well as
  newly synthesized nootropic compounds were able to facilitate the
  development of inhibition during one registration session. Inhibition
  may be used for revealing only selective nootropic drugs devoid of
  sedative and stimulating effects.

Bobkov IuG  Polev PV  Machula AI  Val'dman EA  Soldatov NM  Dudkin SM
[Participation of dihydropyridine-sensitive calcium channels in
  psychotropic effects of nootropic drugs]
Uchastie digidropiridinchuvstvitel'nykh Ca-kanalov v psikhotropnom
  effekte nootropnykh preparatov.
Biull Eksp Biol Med 1990 Oct;110(10):386-9  (Published in Russian)

Administration of Ca-entry blockers with different chemical structure
  before the braining sessions produced the reduction of memory
  retention in mice and rats in the one-trial passive avoidance tests.
  This effect was absent in animals treated immediately after training
  test. Nootropic drugs piracetam and oxiracetam corrected the
  retention of memory when injected just after training test. Chronic
  treatment of rats with increasing doses of the nootropic drugs
  produced about two-fold tissue-specific elevation in the density of
  DHP-receptors, associated with L-type Ca-channels in synaptosomal
  membranes of rat cerebral cortex. Maximal effect was observed in a
  dose of 10 mg/kg. Diltiazem, administrated in a dose of 10 mg/kg,
  produced about two-fold decrease in the receptors density measured 24
  hrs after the first injection. Oxiracetam (10 mg/kg) completely
  antagonized the effect of Ca-entry blocker. These data imply that
  nootropic action of piracetam and oxiracetam is mediated by L-type Ca-

Akhundov RA  Zagorevskii VA  Voronina TA
[Nootropic activity of nicotinamide and its structural analogs]
Nootropnaia aktivnost' nikotinamida i ego strukturnykh analogov.
Biull Eksp Biol Med 1990 Oct;110(10):384-6  (Published in Russian)

It is known that endogenic nicotinamide has a tranquilizing and
  stress-protective activity. The present investigations show the
  nootropic effect of this drug and its analogs nicomorpholine and
  acethylnicotinate on acute models of hypoxia and amnesia. The present
  results revealed that the observed nootropic activity of nicotinamide
  and its analogs is more expressed than this of piracetam, pyritinol
  and meclofenoxate. Having in mind the similarity of pharmacological
  effects of piracetam and nicotinamide (antihypoxic, antiamnestic and
  anxiolytic) we try if these drugs have electronic-structure
  similarities. The analysis revealed some similarity of these drugs'
  molecules in relation to the composition and distribution of polar
  centres pi- and p-electronic areas) distance between them, topography
  of separate molecule parts.

Kresiun VI  Rozhkovskii IaV
[Molecular-biochemical mechanisms of the effects of nootropic agents]
Molekuliarno-biokhimicheskie mekhanizmy deistviia nootropnykh
Biull Eksp Biol Med 1990 Jul;110(7):58-60  (Published in Russian)

It is a known fact that prophylactic hypodermic injection of non-
  typical lithonite tranquillizer in the day's dose of 30 mg/kg during
  10 days prevents the exhaustion of antioxidant system of the body,
  normalizes qualitative and quantitative correlation of separate
  fractions of phospholipids, stabilizes the permeability of
  erythrocytic membranes and prevents the development of
  hypercholesterolemia of the stress. It is concluded that the
  lithonite's stress-protecting effect is the result of its membrane
  stabilizing influence.

Inozemtsev AN  Kokaeva FF  Kozlovskii II  Sarychev EI  Demidov VM
  Tushmalova NA
[Effects of heptapeptide of the tuftsin group with nootropic
  components of action and piracetam on formation of escape reaction in
  normal conditions and in conflict situation]
Vliianie geptapeptida gruppy taftsina s nootropnym komponentom
  deistviia i piratsetama na formirovanie reaktsii izbeganiia v norme i
  pri ee narushenii v usloviiakh konfliktnoi situatsii.
Biull Eksp Biol Med 1990 May;109(5):445-6  (Published in Russian)

In this work we have compared the effect of Tuftsin Group synthetic
  heptapeptide (TP-1) and Piracetam on learning of avoidance response
  and its restoring after disturbance provoked by unexpected changes of
  previously established cause-effect relations in experimental
  environment. We have pointed out that both of the drugs improve
  learning but the dynamics is different, namely: Piracetam causes the
  greatest improvement on the 1st day, meanwhile the Heptapeptide--on
  the 4th day. Both of them preclude from disturbing avoidance response
  and this protective action of peptide is more effective.

Ostrovskaia RU  Trofimov SS
[Nootropic properties of gamma-aminobutyric acid derivatives]
Nootropnye svoistva proizvodnykh gamma-aminomaslianoi kisloty.
Biull Eksp Biol Med 1984 Feb;97(2):170-2  (Published in Russian)

Experiments on rats and mice were made to study the antianamnestic
  and antihypoxic effects of some GABA derivatives. Cetyl GABA, sodium
  and lithium hydroxybutyrates and phenibut were shown to be able to
  decrease the retrograde amnesia caused by electroshock in passive
  avoidance performance. As regards the degree of the antianamnestic
  effect, the above-mentioned non-cyclic derivatives of GABA are not
  inferior to the standard nootropic drug piracetam, a derivative of
  cyclic GABA. Antihypoxic activity of sodium hydroxybutyrate, cetyl
  GABA, phenibut and lioresal studied in experimental hypoxic hypoxia
  compares very favourably with that of piracetam. The compounds under
  consideration manifest their protective action against damaging
  factors in doses which do not provoke muscle relaxation or any types
  of central depression. According to the data obtained one may
  conclude that the nootropic effect is exhibited by not only
  piracetam, a derivative of cyclic GABA, but also by some of its non-
  cyclic derivatives.

Naumova VI  Krylova IN  Drozd IuV  Polev PV  Bashnin IuI
[Comparative influence of nootropic preparations on the emetic effect
  of morphine]
Sravnitel'noe vliianie nootropnykh preparatov na emeticheskii effekt
Biull Eksp Biol Med 1989 Jun;107(6):711-3  (Published in Russian)

The effect of electroshock (ECS) and piracetam, oxiracetam or N-
  acetylglycinamide on the passive avoidance conditioned response in
  rats was studied. The antiemetic effect of the compounds was examined
  in cats as well. The results obtained allowed us to distinct the
  nootropic and antiemetic action of the drugs. The substances
  possessed a similar ability to prevent ECS-induced amnesia. On the
  contrary, oxiracetam completely prevented the emetic response to
  morphine at doses 100 times lower and piracetam at doses 10 times
  higher then those of the opioid. N-Acetylglycinamide had no
  antiemetic activity. The results obtained show that oxiracetam is 100
  times more active in antiemetic test than piracetam. These data
  comprise the novel properties of nootropic drugs.

Rakhmankulova IKh  Voronina TA
[Pharmacological analysis of memory disorders of different origins]
Farmakologicheskii analiz mnesticheskikh narushenii razlichnogo
Biull Eksp Biol Med 1989 Jun;107(6):697-9  (Published in Russian)

The influence of nootropic drugs of different chemical structure and
  mechanism of action (piracetam 200-800 mg/kg, meclofenoxate 50-100
  mg/kg, nicergoline 1-4 mg/kg) on amnestic disturbances induced with
  electroconvulsive shock (ECS), scopolamine (2.5 mg/kg) and phenazepam
  (2.0 mg/kg) was studied in mice using passive avoidance test. All the
  investigated drugs possess distinct protective properties concerning
  different models of amnesia. In ECS-induced amnesia meclofenoxate was
  most effective, in scopolamine-induced amnesia--meclofenoxate and
  nicergoline, in phenazepam-induced amnesia all drugs were equally
  potent in profundity. It is supposed that neurophysiological
  mechanism of action of nootropic drugs is connected with directed
  activation of weakened memory trace of different etiology and its
  transmission into form receivable for transcription.

Savchenko NM  Ostrovskaia RU  Burov IuV
[Normalization of the adaptive avoidance reaction in rats using
  substances with nootropic activity]
Normalizatsiia adaptivnoi reaktsii izbavleniia u krys veshchestvami s
  nootropnoi aktivnost'iu.
Biull Eksp Biol Med 1988 Aug;106(8):170-2  (Published in Russian)

The system of double coaxial cylinders filled with water was used as
  a device for studying simple extrapolation behaviour of rats. The
  amount of rats which were able to dive under the lower edge of the
  inner cylinder, without reaching the bottom of the outer cylinder and
  the latency of this avoidance reaction were considered as a measure
  of extrapolation ability. This reaction was altered by the
  pretreatment of animals with cycloheximide, a protein synthesis
  inhibitor. Piracetam as a standard nootropic, sodium and lithium
  hydroxybutyrate as substances with a potential nootropic effect were
  shown to be able to antagonize the damaging effect of cycloheximide
  on the avoidance performance. Benzodiazepine tranquilizer,
  phenazepam, in contrast to nootropics, evokes additional worsening of
  extrapolation reaction. Normalization of avoidance disturbed by
  cycloheximide, can be used as an adequate and informative approach
  for screening of nootropics.

Krapivin SV  Bogdanov NN  Voronin KE
[Neurophysiological analysis of the correction by nootropic
  substances of disorders in the bioelectric activity of the brain in
  animals during chronic administration of ethanol]
Neirofiziologicheskii analiz korrektsii nootropnymi sredstvami
  narushenii bioelektricheskoi aktivnosti mozga zhivotnykh pri
  khronicheskom vvedenii etanola.
Biull Eksp Biol Med 1988 Jul;106(7):52-6  (Published in Russian)

The influence of some drugs (piracetam and 3-oxypyridine derivative)
  having a nootropic effect on ethanol-induced changes of bioelectrical
  activity was studied in experiments on freely moving rats.
  Discontinuation of ethanol administration (1, 2 g/kg, i.p. for 40
  days) has been found to provoke destructuring of Fourier's spectral
  power of sensorimotor cortex and dorsal hippocamp on the EEG. Long-
  term administration of piracetam or 3-oxypyridine derivative (300 and
  50 mg/kg, respectively, i.p. for 40 days) with ethanol has a
  protective effect and normalizes EEG at the cortical level. The
  authors discuss possible neurophysiological mechanisms of nootropic
  drug action in ethanol-induced pathology.

Voronina TA  Krapivin SV
[New aspects of the neurophysiological mechanism of the action of
  nootropic preparations]
Novye aspekty neirofiziologicheskogo mekhanizma deistviia nootropnykh
Biull Eksp Biol Med 1986 Dec;102(12):721-4  (Published in Russian)

The influence of nootropic drugs on EEG spectral power of the cortex
  and hippocamp was studied in resting rats. All these drugs had a
  specific action on EEG spectral power, causing an increase and
  stabilization of maximum basic distribution peak of the EEG spectral
  power. Such action may be attributed to better organization of
  rhythmic activity in theta-range. The drugs also decreased
  interhemispheric asymmetry of the cortical and hippocampal EEG. The
  authors suggest that the increase and improvement of the basic
  rhythmic activity in the brain and an increased level of distant
  (spatial) synchronization form the basis for the nootropic drug

Voronina TA  Krapivin SV  Nerobkova LN
[Specificity of the action of piracetam, encephabol and Cleregil on
  the transcallosal evoked potential]
Spetsifichnost' deistviia piratsetama, entsefabola i kleregila na
  transkallozal'nyi vyzvannyi potentsial.
Biull Eksp Biol Med 1986 Mar;101(3):320-2  (Published in Russian)

The influence of some drugs having nootropic effect on transcallosal
  evoked potential was studied in the experiments on non-anesthetized
  rabbits. Pyracetam, pyritinol and cleregil have been established to
  increase the amplitude of transcallosal evoked potential. Each of
  these drugs was found to exert specific effects on this
  neurophysiological phenomenon. The authors suggest that transcallosal
  evoked potential can prove helpful in the detection of new drugs with
  possible nootropic effect.

Mondadori C  Bhatnagar A  Borkowski J  Hausler A
Involvement of a steroidal component in the mechanism of action of
  piracetam-like nootropics.
Brain Res 1990 Jan 1;506(1):101-8

Since adrenalectomy abolishes the memory-enhancing effects of
  piracetam and its derivatives, oxiracetam, aniracetam and
  pramiracetam, the question arises whether endogenous steroids play a
  role in their mechanism of action. We show that inhibition of steroid
  biosynthesis by aminoglutethimide and blockade of the aldosterone
  receptors by epoxymexrenone completely suppress the memory-improving
  effects of the nootropics. These results indicate that steroids, or,
  more precisely, activities mediated by the aldosterone receptors,
  might be involved in the mechanism of action of this class of
  nootropics. Blockade of aldosterone receptors, however, does not
  block the effects of cholinomimetics on memory, indicating the
  involvement of another mechanism of action.

Institutional address:
     Pharmaceutical Research Department
     CIBA-GEIGY Limited

Piercey MF  Vogelsang GD  Franklin SR  Tang AH
Reversal of scopolamine-induced amnesia and alterations in energy
  metabolism by the nootropic piracetam: implications regarding
  identification of brain structures involved in consolidation of
  memory traces.
Brain Res 1987 Oct 20;424(1):1-9

Pretreatment with scopolamine, 3 mg/kg, prevented the acquisition of
  a passive avoidance task in rats. These amnesic effects of
  scopolamine could largely be overcome by treatment with 100 mg/kg of
  the nootropic drug piracetam. In order to identify the brain
  structures involved, the effects of these drugs on regional energy
  metabolism were measured throughout the brain, utilizing Sokoloff's 2-
  deoxyglucose autoradiographic procedures. Scopolamine, 3 mg/kg,
  reduced glucose utilization in several areas of the cerebral cortex.
  These effects were largest in the parietal and temporal cortices.
  Other areas affected included the sensorimotor and cingulate
  cortices, the ventral and lateral thalamus, and the dendritic
  neuropil of the CA1, CA2, and CA3 regions of the hippocampus. The
  regional depressions in glucose metabolism observed following
  scopolamine treatment in the rat had some resemblance to depressions
  in glucose metabolism reported for Alzheimer's disease patients in
  positron emission tomography studies. Piracetam, 100 mg/kg, did not
  alter the energy metabolism of any of the 41 brain regions examined.
  However, this dose of piracetam completely reversed the scopolamine-
  induced depressions in the hippocampus. Piracetam partially but
  significantly reversed the scopolamine effects in the cingulate
  cortex. It is concluded that the data provide support for the
  hippocampal-cholinergic theory of memory as originally formulated by
  Meyers and Domino in 1964 and give insight into the mechanisms by
  which nootropics work.

Institutional address:
     Upjohn Company
     MI 49001.

Bartko D  Turcani P  Koprdova I
[Do nootropic substances have only a metabolic effect?]
Maju nootropne latky len metabolicky ucinok?
Cesk Neurol Neurochir 1984 May;47(3):177-83  (Published in Slovak)

Strnad P  Misurec J  Strnadova V
[The effect of nootropic substances on fluctuations in vigilance
  tonus in postinjury pseudoneurasthenia. EEG study]
Vliv nootropnich latek na kolisavy tonus vigility u pourazove
  pseudoneurastenie. EEG studie.
Cesk Neurol Neurochir 1985 Jul;48(4):235-9  (Published in Czech)

Zhu TJ  Chen XY  Pan JC  Zhang SS
[Antagonism of Zn2+ on nootropic action of piracetam in mice]
Chung Kuo Yao Li Hsueh Pao 1990 Mar;11(2):100-2  (Published in Chinese)

In mouse step-down test, the memory impairments of acquisition,
  consolidation and recognition were induced by anisodine,
  chloramphenical and ethanol, respectively. Piracetam 100 mg/(kg.d) ip
  for 5 d improved the anisodine-induced impairment of learning. ZnSO4
  5 mg/(kg.d) po for 5 d did not improve the 3 impairments. Memory
  impairments were enhanced by a combined administration of ZnSO4 and
  piracetam in these 3 models. These results were confirmed by Y-maze
  method in normal mice.

Institutional address:
     Department of Pharmacology
     Wenzhou Medical College

Itil TM  Menon GN  Songar A  Itil KZ
CNS pharmacology and clinical therapeutic effects of oxiracetam.
Clin Neuropharmacol 1986;9 Suppl 3:S70-2

Oxiracetam, a new substance found to be a nootropic in experimental
  pharmacological studies, was tested in three clinical trials: a
  single rising dose tolerance and dose-finding study with quantitative
  pharmaco-electroencephalogram (pharmaco-EEG) and quantitative
  pharmacopsychology in healthy volunteers; a dose-finding study, at
  three dose levels for 3 months, with quantitative pharmaco-EEG in
  mild to moderate dementia patients; and a safety and efficacy study
  with increasing dosages for 12 weeks with subjective and objective
  tests in elderly patients with dementia. In single and repeated oral
  dosages up to 2,400 mg, oxiracetam is a safe compound. According to
  HZI Data Bank Classification Systems, oxiracetam is a vigilance-
  enhancing compound with some effects on spontaneous memory. The
  therapeutic effect of oxiracetam can be discriminated from placebo,
  and in comparison with piracetam, oxiracetam exhibits greater
  improvement in memory factor.

Barreca T  Gallamini A  Murialdo G  Nizzo MC  Polleri A
[Significance of blood levels of prolactin and somatotropin as
  indices of pharmacological effects on the central nervous system]
Significato dei livelli sierici di prolattina e somatotropo quali
  indici di effetti farmacologici sul sistema nervoso centrale.
Clin Ter 1978 Jul 31;86(2):147-59  (Published in Italian)

Lehmann HE
Psychopharmacological approaches to the organic brain syndrome.
Compr Psychiatry 1983 Sep-Oct;24(5):412-30

Spagnoli A  Tognoni G
'Cerebroactive' drugs. Clinical pharmacology and therapeutic role in
  cerebrovascular disorders.
Drugs 1983 Jul;26(1):44-69

While their importance in the market-place is steadily increasing in
  developed (mainly continental Europe) and even in developing
  countries, compounds included in the broad category of
  'cerebroactive' drugs hardly rate a mention in reference pharmacology
  and therapeutics textbooks. It is an undeniable fact, however, that
  the principal users or targets of this drug class, mainly elderly
  people, represent an increasingly worrying problem, with their often
  puzzling cohort of ill-definable and even less predictable
  neurological and mental symptoms. The combination of the above
  factors cannot but produce a rather confused situation, in which the
  pressure to treat and the adherence to scientifically rigorous
  assessment are likely to prevail alternately, on a purely casual
  basis. This review aims to provide sound methodological guidelines
  for assessment of 'cerebroactive' drugs in a not always easily
  accessible literature. It covers firstly the general problems of
  stroke, dementia and 'common symptoms' of the elderly, and then looks
  in detail at those compounds which have to date attracted most
  attention (ergot derivatives, cinnarizine, flunarizine, vincamine,
  eburnamonine, naftidrofuryl, oxpentifylline, piracetam and
  citicoline), as well as those which are currently considered
  investigational (choline and lecithin). The pharmacology and
  available clinical studies of each drug are examined. No therapeutic
  indication can be derived from the available evidence, as the few
  positive results do not go beyond random improvement of symptoms.
  More fundamentally, the lines of research which need to be pursued
  most intensively relate to better preliminary definition of
  diagnostic and prognostic criteria and, with the establishment of
  adequate testing tools for the assessment of behaviour and
  neuropsychological performance, those basal conditions which are
  modified 'naturally' or by drugs.

Hollister LE
Alzheimer's disease. Is it worth treating?
Drugs 1985 Jun;29(6):483-8

Krylova IN  Antonova LV  Kamenskii AA  Iasnetsov VV
[A comparative study of the nootropic properties of piracetam and
Sravnitel'noe izuchenie nootropnykh svoistv piratsetama i
Farmakol Toksikol 1991 Jan-Feb;54(1):14-6  (Published in Russian)

The behavioral activities of piracetam and oxiracetam were studied
  during the learning tests (active avoidance, passive avoidance, T-
  maize). The levels of the orientation reaction and emotionality of
  the animals were determined by the "open field" method. To achieve
  similar effects, injections of 10 mg/kg of oxiracetam and 100 mg/kg
  of piracetam intraperitoneally were required. Both nootropics
  facilitated the learning of the animals but failed to change their
  behavior in the open field. Piracetam was more effective in the
  active avoidance test and oxiracetam in the T-maize test. The data
  indicate some differences in the activities of piracetam and

Kovaleva EL
[Comparative characteristics of the nootropic action of fenibut and
Sravnitel'naia kharakteristika nootropnogo deistviia fenibuta i
Farmakol Toksikol 1984 Jan-Feb;47(1):20-3  (Published in Russian)

The nootropic effects of phenibut and phepyrone administered in low
  doses were studied and compared in experiments on rats. Experiments
  made in a water maze and a shuttle box demonstrated that both
  phepyrone and piracetam improved the learning performance in rats. In
  the doses tested phenibut did not produce any nootropic activity.

Raevskii KS
[Neurochemical aspects of the pharmacology of GABAergic substances]
Neirokhimicheskie aspekty farmakologii GAMK-ergicheskikh veshchestv.
Farmakol Toksikol 1981 Sep-Oct;44(5):517-29  (Published in Russian)

Zaitsev IuV  Shabanov PD  Bogoslovskaia SI  Krauz VA  Fisher KhD
[The significance of the antihypoxic properties of etimizol in its
  nootropic action]
Znachenie antigipoksicheskikh svoistv etimizola v ego nootropnom
Farmakol Toksikol 1988 Sep-Oct;51(5):27-30  (Published in Russian)

The antihypoxic effects of etimizol and other nootropics are analysed
  on various experimental models of hypoxia and during bicycle
  ergometric exercise in healthy volunteers. Etimizol was shown to
  relieve amnesia effectively in the origin of which there is the
  hypoxic component (hypobaric hypoxia, actinomycin D, mechanical
  injury of the brain). The advantage of etimizol as compared to other
  nootropics with similar action (meclofenoxate, piracetam) is its high
  effectiveness at a single administration.

Krapivin SV  Voronina TA
[Comparative neurophysiological study of the nootropic drugs
  piracetam and centrophenoxine]
Sravnitel'noe neirofiziologicheskoe issledovanie nootropnykh
  preparatov piratsetama i tsentrofenoksina.
Farmakol Toksikol 1987 Nov-Dec;50(6):17-20  (Published in Russian)

Effects of nootropic drugs on transcallosal evoked potential (TEP)
  and EEG spectra of the animal brain cortex and hippocamp were
  studied. It was found that piracetam and centrophenoxine exert
  similar effects on the amplitude of the primary TEP components,
  produce its increase and also a rise and stabilization of the
  predominant peak in distribution of EEG power spectrum that
  corresponds to the improvement of theta rhythm organization. The
  drugs exert different effects on the secondary positive TEP
  component; centrophenoxine induces a change in non-basic rhythm of
  EEG in rats. Based on the results obtained, the authors consider
  possible neurophysiological mechanisms of the nootropic effect and
  make a comparative analysis of the actions of the drugs.

Zimakova IE  Makarchikov NS  Karpov AM
[Evaluation of the nootropic effect of mebikar in clinical practice]
Otsenka nootropnogo effekta mebikara v klinicheskoi praktike.
Farmakol Toksikol 1986 Sep-Oct;49(5):50-3  (Published in Russian)

Mebicar therapy resulted in a reduction of the degree of deficient
  disorders of thinking in 27 of 50 patients with paranoid
  schizophrenia and normalization of indices of mental working
  capacity, attention and memory, shortening of the time of visual-
  motor disjunctive reaction in 50 patients with borderline states.
  Mebicar was shown to possess a nootropic effect which differs
  qualitatively from that of piracetam.

Karkishchenko NN  Khaitin MI
[Comparative study of the indices of the antidepressive activity of
  potassium orotate and piracetam]
Sravnitel'noe issledovanie nekotorykh pokazatelei antidepressivnoi
  aktivnosti kaliia orotata i piratsetama.
Farmakol Toksikol 1985 Mar-Apr;48(2):32-5  (Published in Russian)

It has been established in mouse experiments that potassium orotate
  (100 mg/kg) and piracetam (500 mg/kg) given in chronic oral doses
  have an antidepressant activity according to the "behavioral despair"
  test. It has been demonstrated that antidepressant activity of
  potassium orotate (20 and 50 mg/kg) and piracetam (50 and 100 mg/kg)
  is associated with a psychostimulant effect.

Goel RK  Chakravarty M  Abbas WR  Singh KP  Bhattacharya SK
Effect of piracetam, a nootropic agent, on experimental gastric
  ulcers in rat.
Indian J Exp Biol 1990 Apr;28(4):337-40

Piracetam, used clinically for cognitive disorders, was found to have
  significant anti-ulcerogenic activity against immobilization stress-
  and aspirin-induced gastric ulcers in rats. The anti-ulcer effect of
  piracetam was exerted by augmentation of mucosal resistance. This was
  indicated by the significant attenuation of the decrease in total
  carbohydrate: protein ratio induced by aspirin. It also reversed the
  marked increase in gastric juice protein and DNA induced by aspirin,
  indicating that piracetam attenuated the augmented mucosal cell
  exfoliation induced by the ulcerogen. The drug also increased gastric
  mucosal serotonin concentrations. Piracetam, thus appears to have a
  profile of activity associated with cytoprotective agents.

Institutional address:
     Department of Pharmacology
     Banaras Hindu University

Jaiswal AK  Upadhyay SN  Bhattacharya SK
Effect of piracetam, a nootropic agent, on discrimination learning
  deficits induced by parental undernutrition and environmental
  impoverishment in young rats.
Indian J Exp Biol 1989 Mar;27(3):269-73

The study was conducted on 64 Charles Foster albino rats which were
  equally distributed into 8 even-matched groups, following a 2 x 2 x 2
  factorial design by varying three independent factors at two levels:
  nutrition--normal and undernutrition, environmental--enrichment and
  impoverishment, and drug treatment--vehicle and piracetam (100 mg/kg,
  ip). Prenatal nutrition was induced by restricting the mother's food
  intake. The environmental enrichment/impoverishment and the
  vehicle/drug treatments were given during the postweaning period of
  the rat pups. The animals were subjected to original and subsequent
  reversal brightness discrimination learning tests in a single unit T-
  maze at 8-9 weeks of age. The results indicate that undernutrition
  and environmental impoverishment significantly attenuated the
  original discrimination as well as the reversal discrimination
  learning. Piracetam treatment improved the learning performance of
  normally reared rats and also attenuated the original and reversal
  learning deficits induced by prenatal undernutrition and postnatal
  impoverishment. The results indicate that piracetam may be useful in
  memory deficits induced by malnutrition.

Bhattacharya SK  Upadhyay SN  Jaiswal AK  Bhattacharya S
Effect of piracetam, a nootropic agent, on rat brain monoamines and
Indian J Exp Biol 1989 Mar;27(3):261-4

Piracetam is the prototype of a new class of psychotropic drugs, the
  nootropic agents, which are claimed to selectively improve the higher
  telencephalic integrative activities. The effect of piracetam on rat
  brain monoamines and prostaglandins (PGs) was assessed so as to
  garner information on its mode of action. Two doses of the drug were
  used, a lower dose (20 mg/kg ip) and a higher dose (100 mg/kg, ip),
  the latter being known to exert a facilitatory effect on learning and
  memory. Piracetam produced a dose-related effect on rat brain
  serotonin (5HT) and noradrenaline (NA), with the lower dose inducing
  a decrease in 5HT levels and an increase in NA concentrations. The
  higher dose of piracetam produced the opposite effect. Dopamine (DA)
  levels were not significantly affected. The lower dose of the drug
  attenuated 5HT turnover and augmented that of NA, whereas the higher
  dose of piracetam produced the reverse effects, in clorgyline treated
  rats. The lower dose of piracetam produced a slight and statistically
  insignificant increase in rat brain PGE2 and PGF2 alpha. However, the
  higher dose of the drug produced marked increase in the levels of
  both the PGs. The observed biochemical effects may provide a basis
  for the nootropic effect of piracetam. However, they may also be due
  to the GA-BA-mimetic action of the drug, particularly those observed
  with the lower dose of piracetam.

Saletu B  Grunberger J  Linzmayer L  Stohr H
Encephalotropic and psychotropic effects of intravenous buflomedil in
  the elderly: double-blind, placebo-controlled pharmaco-EEG and
  psychometric studies.
Int J Clin Pharmacol Res 1984;4(2):95-107

In a double-blind placebo-controlled study, the encephalotropic and
  psychotropic properties of intravenously administered buflomedil--a
  new vasoactive drug--were studied in 10 elderly volunteers in their
  60s by means of quantitative EEG and psychometric analyses. At weekly
  intervals the patients received randomized (latin square design),
  single, intravenous doses of placebo, 50 mg, 100 mg and 200 mg
  buflomedil as well as 2000 mg piracetam as reference substance. EEG
  recordings and the monitoring of blood pressure, heart rate and side-
  effects were carried out at hours 0, 1, 2, 4, 6 and 8. Psychometric
  tests were performed at hours 0, 2, 4, 6 and 8. Computer-assisted
  spectral analysis of the EEG demonstrated that buflomedil exerted a
  significant effect on the central nervous system (CNS) as compared
  with placebo, characterized by a decrease of delta and theta,
  increase of alpha and alpha-adjacent beta activity as well as by an
  acceleration of the centroid of the alpha activity and also of the
  total activity. 2 g piracetam induced the same type of changes only
  at the end of the recording day. These quantitative EEG changes have
  been previously observed after several antihypoxidotic/nootropic
  drugs and indicate an improvement in vigilance in the sense of Head.
  Treatment-efficacy calculations demonstrated that 200 mg buflomedil
  was the most CNS-effective substance followed by 100 mg and 50 mg
  buflomedil and 2 g piracetam. Time-efficacy calculations showed that
  the encephalotropic effects were already marked in the 1st hour after
  i.v. application, decreased to a low in the 4th hour and subsequently
  increased again to reach a maximum in the 8th hour. In contrast, 2 g
  piracetam induced CNS changes which increased from the 1st throughout
  the 6th hour to show only a slight decline thereafter. The hysteresis
  between pharmacodynamic and pharmacokinetic findings is discussed.
  Psychometric investigations demonstrated that after 50 mg buflomedil
  i.v. there was a significant improvement as compared with placebo in
  cognitive function based on the Pauli test as well as an increase in
  correct reactions in the alphabetical reaction test. Doses of 100 mg
  buflomedil also produced an improvement in the Pauli test, attenuated
  errors in the reaction time task, improved complex reaction on the
  Vinnese Determinationsgerat, increased CFF but also errors in the
  concentration test.

Gualtieri CT  Golden RN  Fahs JJ
New developments in pediatric psychopharmacology.
J Dev Behav Pediatr 1983 Sep;4(3):202-9

This is a report on recent developments in pediatric
  psychopharmacology: new drugs and new applications for established
  drugs. The drugs reviewed include imipramine, amitryptiline, lithium,
  piracetam, propranolol, tryptophan, clonidine, pyridoxine and
  fenfluramine. Putative indications include prepubertal depression,
  school phobia, anorexia nervosa, explosive-aggressive behavior,
  learning disabilities, attention deficit disorder (hyperactivity),
  Tourette's syndrome, autism, and the Lesch-Nyhan syndrome. Some of
  the information presented in this report must be regarded as
  "preliminary," and caution is advised in its interpretation and

Biological correlates of piracetam clinical effects in psychotic
J Int Med Res 1979;7(4):277-84

The purpose of this controlled clinical trial was to demonstrate
  possible correlations between changes in bioenergetic metabolism and
  psychotropic drug administration in the treatment of functional
  psychosis. The study included twenty-six patients, eleven with
  schizophrenia, three with chronic atypical depression and twelve with
  drug-resistant endogenous depressions. All patients were kept on
  continuous psychotropic medication for at least 3 weeks before
  starting the trial, and piracetam was given additionally in a fixed
  dosage of 2400 mg daily; the same number of identical capsules was
  given during the pre- and post-treatment placebo periods. Psycho-
  pathological evaluation of the patients was by the BPRS; clinical and
  biochemical data were evaluated statistically by the analysis of
  regression. The results show that in schizophrenic patients an
  improvement was observed in those cases who had improved
  biochemically, i.e. where the ATP values had increased. In drug-
  resistant depressions there was a rapid and significant clinical
  improvement after piracetam co-administration, and this went in step
  with a significant rise in ATP levels.

Shubina TI  Zaitsev VP
[Experience using nootropil in patients with chronic ischemic heart
Opyt primeneniia nootropila u bo'lnykh khronicheskoi bolez'niu
Klin Med (Mosk) 1989 May;67(5):36-8  (Published in Russian)

Course nootropil treatment was conducted in 34 IHD patients with
  neurotic and neurotic-like diseases. Dynamic changes in the psychic
  state were assessed by the clinical scale and the MMPI psychological
  test. Significant improvement or normalization of the psychic state
  was achieved in 58.8 per cent of the patients treated with nootropil.
  The best results were obtained in the treatment of asthenic states.
  Administration of nootropil had no influence on the incidence of
  angina pectoris attacks and produced no side effects.

Shabanov PD  Grinenko AIa  Kalishevich SIu
[Use of preparations from the nootropic group for treating memory
  disorders in chronic alcoholism]
Ispol'zovanie preparatov gruppy nootropov dlia lecheniia narushenii
  pamiati pri khronicheskom alkogolizme.
Klin Med (Mosk) 1988 Sep;66(9):114-6  (Published in Russian)

Buliusin VIa  Besschetnova AI  Shabanov PD
[Hyperbaric oxygenation and nootropic agents in the treatment of
  exacerbation of peptic ulcer]
Giperbaricheskaia oksigenatsiia i nootropy v lechenii obostrenii
  iazvennoi bolezni.
Klin Med (Mosk) 1987 Oct;65(10):56-8  (Published in Russian)

Binder S
[The activity of the nootropic substance piracetam on the cortical
  performance of chronic alcoholics (author's transl)]
Die Wirkung des Nootropikums Piracetam auf die kortikale Leistungs-
  fahigkeit chronischer Alkoholiker
MMW 1974 Nov 29;116(48):2127-30  (Published in German)

de Angelis L
The differential effects of post-session administration of amineptine
  and imipramine on memory processes in mice.
Methods Find Exp Clin Pharmacol 1990 Jan-Feb;12(1):23-7

The effects of post-trial administration of amineptine, a
  dopaminergic antidepressant drug, were compared with those of memory-
  facilitating (strychnine, piracetam) or impairing drugs
  (phenobarbital, imipramine) on an experimental model of memory. Mice
  were given two sessions in open-field test and the decrease in
  activity at the second session (habituation) served as an index of
  retention. The good retention observed with a 1-day inter-session
  interval was impaired by post-session administration of phenobarbital
  (10 mg/kg i.p.) or imipramine (5.0 mg/kg i.p.). The poor retention
  observed with a 5-day inter-session interval was enhanced by post-
  session administration of strychnine (0.20 mg/kg i.p.), piracetam
  (1000 mg/kg i.p.) and amineptine (10 mg/kg i.p.). These findings show
  that different profiles of cognitive and psychomotor effects were
  produced by imipramine and amineptine. Amineptine, lacking sedative
  and anticholinergic properties which are characteristic of
  imipramine, interferes positively with learning and memory, in a
  manner similar to piracetam and strychnine.

Institutional address:
     Istituto di Farmacologia
     Facolta di Medicina e Chirurgia
     Universita di Trieste

Lazarova-Bakarova MB  Genkova-Papasova MG
Influence of nootropic drugs on the memory-impairing effect of
  clonidine in albino rats.
Methods Find Exp Clin Pharmacol 1989 Apr;11(4):235-9

The effects of four nootropic drugs (piracetam, aniracetam,
  meclofenoxate and fipexide) on cognitive functions impaired by the
  antihypertensive drug clonidine were investigated in albino rats. The
  changes in learning and memory were studied by two-way active
  avoidance with punishment reinforcement (shuttle box). Clonidine
  injected intraperitoneally at a dose of 0.1 mg/kg immediately after a
  one-day shuttle box training significantly impaired retention. A 5-
  day treatment before the training session with piracetam 600 mg/kg,
  aniracetam 50 mg/kg, meclofenoxate 100 mg/kg and fipexide 10 mg/kg
  completely abolished the memory-impairing effect of clonidine. The
  role of the NAergic neurotransmitter system in the clonidine-induced
  disturbances of cognition, as well as in the protective effects of
  nootropic drugs, was discussed.

Institutional address:
     Institute of Physiology
     Bulgarian Academy of Sciences

Valzelli L  Kozak W  Banfi L
Exploratory behavior and the dual activity of some psychoactive
  drugs: Part II.
Methods Find Exp Clin Pharmacol 1987 Dec;9(12):807-9

Exploration is an essential, life-preserving component of animal
  higher nervous functions. The experiments presented here show that
  exploratory behavior may differ according to the experimental
  subject's emotional baseline, and that exploratory performance is
  accordingly affected differently by some nutrients and central

Institutional address:
     Istituto di Ricerche Farmacologiche Mario Negri

Herrmann WM  Coper H
Are nootropics a separate class of drugs? A differentiation in
  various models.
Methods Find Exp Clin Pharmacol 1987 Mar;9(3):173-82

Psychostimulants, analeptics, and nootropics are three classes of
  drugs that have been used with varying success in the treatment of
  impaired brain functions. They all produce an excitatory and
  disinhibitory effect on the CNS but can be distinguished through
  their characteristic properties. Psychostimulants are drugs that lead
  to a general, but nonphysiological activation, which is followed by a
  phase of inhibition. Analeptics are drugs that stimulate the CNS, in
  particular the respiratory and circulatory centers, and which in high
  doses lead to convulsions. Nootropics are drugs that (in impaired
  brain functions) lead to a physiological activation of adaptation.

Morelli A  Bossi L
[Value of a new medical treatment of neurogenic bladder: piracetam]
Validita di un nuovo trattamento medico della vescica neurogena: il
Minerva Urol 1974 Jul-Aug;26(4):176-81  (Published in Italian)

Bandoli G  Clemente DA  Grassi A  Pappalardo GC
Molecular determinants for drug-receptor interactions. 1. Solid-state
  structure and conformation of the novel nootropic agent 2-pyrrolidone-
  N-acetamide: X-ray and theoretical SCF-MO studies.
Mol Pharmacol 1981 Nov;20(3):558-64

Sano M  Stern Y  Marder K  Mayeux R
A controlled trial of piracetam in intellectually impaired patients
  with Parkinson's disease.
Mov Disord 1990;5(3):230-4

Twenty patients with Parkinson's disease and marked intellectual
  impairment or dementia participated in a double-blind placebo
  controlled trial of the nootropic, piracetam. A standardized
  neurological examination, a neuropsychological test battery, and a
  functional scale, The Sickness Impact Profile, were completed for all
  patients. They were then assigned by blind randomization to drug or
  placebo conditions receiving 3.2 g of piracetam or an identical
  amount of placebo for 12 weeks. The dose was increased to 4.8 g for
  an additional 12 weeks. Neurological, psychological, and functional
  measures were rated as improved, unchanged, or worsened in comparison
  to baseline performance. Twenty-five percent of the patients did not
  complete the trial for reasons unrelated to the medication. Although
  there was a significant improvement on one subtest of the functional
  scale, no significant effects were demonstrated in cognitive or
  neurological measures.

Institutional address:
     Department of Neurology
     College of Physicians and Surgeons
     Columbia University
     New York
     New York.

Herrmann WM  Kern U
[Nootropic drugs: effects and effectiveness. A reflection exemplified
  by a phase III study using piracetam]
Nootropika: Wirkungen und Wirksamkeit. Eine Uberlegung am Beispiel
  einer Phase III-Prufung mit Piracetam.

Nervenarzt 1987 Jun;58(6):358-64  (Published in German)

Klawans HL  Genovese N
Pharmacology of dementia.
Neurol Clin 1986 May;4(2):459-67

The authors discuss cerebral vasodilators, cerebral metabolic
  enhancers, nootropics, opioid antagonists, psychostimulants,
  cholinergic agents, and neuropeptides. Their efficacy in the
  treatment of dementing illnesses is evaluated.

Wasilewski R  Lebiediewa N  Kozlowa E  Wolkow W
[Comparative evaluation of psychoactive drugs used in patients with
  subacute and chronic cerebrovascular disorders]
Ocena porownawcza skutecznosci lekow psychoenergizujacych u chorych z
  podostrymi i przewleklymi zaburzeniami kra~zenia mozgowego.
Neurol Neurochir Pol 1981 Jul-Aug;15(4):447-51  (Published in Polish)

The report is based on 315 patients with subacute and chronic
  cerebral circulatory disturbances caused mostly by atherosclerosis
  aged 30 to 82 years, treated for 1-6 months. In 90 cases Piracetam
  (Nootropil) was given, 107 received Piritinol (Encephabol, Enerbol),
  77 Piriditol, 41 Centrophenoxin. The patients were allocated randomly
  to these groups. In the treated patients improvement was achieved in
  a considerable proportion of cases (44-82%) treated with different
  drugs. This improvement manifested itself as regression or decreased
  intensity of neurotic complaints, labyrinthine-cerebellar signs,
  pyramidal signs, anxiety and fears, improvement of recent memory,
  attention, psychomotor activity. The best results were obtained with
  Nootropil, moderately good with Centrophenoxin, Encephabol, and poor
  with Piriditol. Drug tolerance was best with Encephabol, while that
  of other drugs was slightly worse. The only disquieting symptoms was
  activation of epileptic seizures in several patients treated with
  Nootropil or Centrophenoxin. The best way of administration was
  giving the drugs in two doses in the morning hours and at noon. The
  authors regard as useful the treatment of patients with subacute and
  chronic cerebral circulatory failure with psychoenergizing drugs.

Sannita WG  Ottonello D  Perria B  Rosadini G  Timitilli C
Topographic approaches in human quantitative pharmaco-
Neuropsychobiology 1983;9(1):66-72

The scalp distribution of the quantitative EEG effects of neuroactive
  compounds was studied in a number of pharmaco-EEG investigations, in
  which comparable procedures for EEG recording and processing were
  applied: power spectral and amplitude analyses were combined in all
  studies. Topographic differentiations were observed. These could
  include intrahemispheric and/or interhemispheric dissimilarities in
  the distribution of EEG effects common to the explored electrode
  derivations, as well as drug effects detectable only in distinct
  areas. The distribution could vary depending upon the EEG parameter
  considered; it was restricted to drug-related EEG modifications in
  all cases.
Valzelli L  Bernasconi S  Coen E  Petkov VV
Effect of different psychoactive drugs on serum and brain tryptophan
Neuropsychobiology 1980;6(4):224-9

A considerable amount of evidence indicates that the brain tryptophan
  level depends on circulating tryptophan. Changes of tryptophan
  concentration have also been described to modify the activity of
  benzodiazepines and tricyclic antidepressants. In the present study,
  a series of psychoactive drugs have been preliminarily screened for
  their activity on brain and plasma tryptophan levels. The results
  obtained suggest that tryptophan may be involved to varying extents
  in the activity of different psychoactive compounds.

Emilien G
Effect of drugs acting on monoaminergic and cholinergic systems on
  the quantified EEG of rats.
Neuropsychobiology 1989;21(4):205-15

Five different classes of drugs (clonidine: 0, 0.10, 0.30, 0.50
  mg/kg; yohimbine: 0, 2, 4, 8 mg/kg; haloperidol: 0, 0.02, 0.04, 0.08
  mg/kg; piracetam: 0, 150, 300, 600 mg/kg, and eserine: 0, 0.10, 0.30,
  0.50 mg/kg) were studied on two cortical EEG derivations as well as a
  deep structure, the locus ceruleus in the rats. Each drug affected
  the EEG in its own particular manner. Clonidine significantly
  decreased frequency in the theta band (3.7-7.5 Hz) and increased it
  in the alpha band (7.6-13.5 Hz). A general significant increase in
  power was observed. Yohimbine's effects on the EEG varied according
  to the regions studied. There were significant modifications of power
  and frequency in the theta, alpha and beta bands in the three
  derivations studied. Notable effects of haloperidol were observed as
  an increase in power in all frequency bands at all doses administered
  particularly in the anteroparietal and posteroparietal derivations.
  In the locus ceruleus derivation, power was significantly increased
  at all doses only in the alpha and beta frequency bands. Concerning
  piracetam, while no significant effects were noted on the EEG
  frequency, this drug significantly increased EEG power in the
  posteroparietal and anteroparietal derivations. The most important
  effects are obtained at the lowest dose (150 mg/kg) administered.
  Finally, it was shown that eserine significantly decreased power in
  the delta bandwidth shortly after its administration. Afterwards, the
  power gradually regained its original level.

Institutional address:
     Laboratory of Pharmacology
     University of Liege

Sarter M
Some considerations of different modes of action of nootropic drugs.
Neuropsychobiology 1986;15(3-4):192-200

Four possible types of nootropic drugs are classified theoretically
  according to their possible effects on cognitive functions. Among the
  factors usually varied in psychopharmacological designs, the
  significance of the time of application of the drug is stressed.
  Considering the relations between the time of application of
  nootropic drugs within standardized experimental plans and their
  effects on cognitive processes, ideal time of application-response
  curves for each of these types of nootropic compounds are proposed.
  These curves may represent experimental tools in investigating the
  mode of action of nootropic drugs. Finally, some experimental results
  are presented which are relevant to this approach. Overall, however,
  the rationale of these theoretical considerations remains largely
  unproven because of the lack of studies to date designed to evaluate
  the mechanisms of drug action by varying the time of application of a
  nootropic compound.

Satoh M  Ishihara K  Katsuki H
Different susceptibilities of long-term potentiations in CA3 and CA1
  regions of guinea pig hippocampal slices to nootropic drugs.
Neurosci Lett 1988 Nov 11;93(2-3):236-41

Effects of the nootropic drugs, piracetam and bifemelane, on long-
  term potentiation (LTP) of population spikes in the CA3 and CA1
  regions of guinea pig hippocampal slices were investigated. Piracetam
  (10(-6) to 10(-4) M) and bifemelane (10(-8) to 10(-6) M)
  significantly augmented the LTP in the CA3 region. The effects of
  these drugs were inhibited by scopolamine (10(-6) M). However, the
  LTP in the CA1 region was not affected by piracetam and bifemelane
  even at highly effective concentrations (10(-5) and 10(-6) M,
  respectively). Thus, the LTP in the CA3 is more susceptible to
  nootropic drugs than in the CA1.

Institutional address:
     Department of Pharmacology
     Faculty of Pharmaceutical Sciences
     Kyoto University

Hirai S
[Drug therapy of Alzheimer's disease. Problems of the criteria of
  clinical trials of nootropic drugs]
Nippon Rinsho 1988 Jul;46(7):1592-9  (Published in Japanese)

Mondadori C  Petschke F  Hausler A
The effects of nootropics on memory: new aspects for basic research.
Pharmacopsychiatry 1989 Oct;22 Suppl 2:102-6

The mechanism through which nootropics of the piracetam type (i.e.,
  piracetam itself and its analogues oxiracetam, pramiracetam, and
  aniracetam) improve memory is still uncertain. Its elucidation will,
  however, not only mark an advance in the treatment of cognitive
  disorders, but also shed light on the basic processes of memory
  storage. Although the great majority of the findings available so far
  seem to suggest cholinergic mechanisms, divergent results are
  obtained whenever parallel experiments are performed with two or more
  of these compounds. More recent observations indicate that
  interactions with steroids take place. All four compounds are
  inactive in adrenalectomized laboratory animals; chemical blockade of
  the adrenal cortex with aminoglutethimide and pretreatment which
  epoxymexrenon, a potent mineralocorticoid antagonist, eradicated the
  memory-enhancing effect of all four substances.

Institutional address:
     Pharmaceutical Research Department
     CIBA-GEIGY Limited

Lindner G  Grosse G  Plonka G
[The effects of certain psycho- and coronary therapeutic agents on
  nerve tissue in vitro]
Uber die Wirkung einiger Psycho- und Coronartherapeutica auf das
  Nervengewebe unter in-vitro-Bedingungen.
Pharmazie 1978 Aug;33(8):534-6  (Published in German)

Stroescu V  Constantinescu I  Brezina A  Nicogosian-Lapusneanu G
Comparative experimental research into the nootropic action of
  procaine and pyracetam.
Physiologie 1983 Oct-Dec;20(4):271-81

Procaine exerts a positive influence in different tests that prove
  its nootropic effects: it improves the learning process in small
  animals, increases the resistance to hypoxemia induced by
  curarization and hypobarism, augments the effort endurance. The
  effect is clearly shown at the dose of 5 mg/kg b.w. in subchronic
  treatment (five to eight days). A higher dose of procaine--25 mg/kg
  b.w.--does not influence significantly these tests, but ensures a
  partial protection against gastric ulcers induced by contention. The
  efficiency is inferior to pyracetam. Neither procaine nor pyracetam
  succeeds in protecting against supramaximal electroshock or in
  influencing EEG changes due to hexobarbital. As shown by EEG, the two
  substances have different mechanisms of action: procaine triggers
  cortical inhibitory effects while pyracetam manifests itself by
  activating phenomena.

Westermann KH  Schmidt J  Bucher U
Effects of nootropic drugs on dopaminergic systems in the CNS.
Pol J Pharmacol Pharm 1981 Nov;33(4):431-6

The effect of 3 nootropic drugs, meclofenoxat (MEC), piracetam (PIR)
  and orotic acid (methylglucamine orotate, MGO), on locomotor activity
  and on rotational behavior after intracerebral injection of dopamine
  was tested in female Wistar rats. Whereas MGO-pretreatment increased
  the dopaminergic supersensitivity following repeated haloperidol in
  both behavioral tests, the other nootropics were without influence on
  intensity and duration of supersensitivity. Stimulating and sedative
  action of apomorphine on locomotion (following 2 mg/kg and 40
  micrograms/kg apomorphine sc, respectively) was found to be unchanged
  after single doses of nootropics (300 mg/kg PIR or MEC, 225 mg/kg
  MGO, 30 min before apomorphine). Preceding systemic application of
  nootropics did not change the rotational behavior following
  application of dopamine (200 micrograms/2 microliters) into nucleus
  accumbens or nucleus caudatoputamen. The results show that nootropic
  drugs are without influence on spontaneous and dopaminergically
  stimulated locomotor activity but in contrast to PIR and MEC, MGO is
  able to facilitate the dopaminergic supersensitivity.

Schmidt J
New aspects in the pharmacology of kindling implications for
  mechanism of of action in kindling.
Pol J Pharmacol Pharm 1987 Sep-Oct;39(5):527-36

Kindling is a long-lasting, transsynaptic, pathway-specific plastic
  change in brain function. It has been proposed as a model of neural
  plasticity, learning and memory, as well as a model of epilepsy. To
  elucidate the action of substances characterized by their ability to
  improve learning and memory and to have an activatory, protective and
  function restoring effect on nerve cells in distress, the effects of
  nootropic drugs and of antioxidative acting substances on the
  development of kindling and the seizure behavior in the kindled state
  were investigated. Nootropic drugs suppress the development of
  pentetrazol (PTZ)- and amygdala-kindling and possess anticonvulsive
  potency preferentially in kindled rats. In comparison to amygdala-
  kindling the substances were found to be more effective against PTZ-
  kindled seizures. Chemically different antioxidants in doses known to
  scavenge free radicals suppress markedly the development of kindling
  and possess anticonvulsant potency in chemically and electrically
  kindled- rats.
     Institute of Pharmacology and Toxicology
     Medical Academy Carl Gustav Carus
Oehler J  Jahkel M  Schmidt J
The influence of chronic treatment with psychotropic drugs on
  behavioral changes by social isolation.
Pol J Pharmacol Pharm 1985 Nov-Dec;37(6):841-9

Neurobiological changes induced by social isolation of mice are
  affected by several drugs in different manner. Lithium is able to
  prevent changes in head-twitches seen after short term isolation as
  well as enhanced aggressivity and enhanced spontaneous locomotion
  demonstrable after long term isolation. Similar to lithium are the
  effects of carbamazepine, whereas the other tested substances: Ca-
  valproate, diazepam, desipramine, clomipramine as well as piracetam,
  methylglucaminorotate and meclofenoxate show different effects. The
  model of social isolation is discussed in view of its ability to
  differentiate the qualities of chronic drug administration during
  functional dynamic changes of the CNS in animals.

Janicki PK  Rewerski W
[Evaluation of drugs used in geriatric neuropharmacology]
Przeglad lekow stosowanych w neurofarmakologii geriatrycznej.
Pol Tyg Lek 1985 Dec 23-30;40(51-52):1417-21  (Published in Polish)

Saletu B  Grunberger J
Antihypoxidotic and nootropic drugs: proof of their encephalotropic
  and pharmacodynamic properties by quantitative EEG investigations.
Prog Neuropsychopharmacol 1980;4(4-5):469-89

Sansone M  Oliverio A
Avoidance facilitation by nootropics.
Prog Neuropsychopharmacol Biol Psychiatry 1989;13 Suppl:S89-97

1. The effects on avoidance acquisition of two nootropic drugs,
  oxiracetam and piracetam, were tested in mice subjected to five daily
  100-trial training sessions in the shuttle-box. 2. Oxiracetam (25 or
  50 mg/kg/i.p.) and piracetam (100 mg/kg/i.p.), given before each
  daily session, improved avoidance acquisition in the good performing
  BALB/c more than in the poor performing C57BL/6. In both cases
  avoidance facilitation was evident only if training was preceded by a
  five-day pretreatment. 3. Combinations of nootropics and
  methamphetamine increased avoidance responses in C57BL/6 mice more
  than drugs given separately. Conversely, no interaction occurred in a
  locomotor activity test. 4. Interactive effects in the learning
  situation, but not in a test of general activity, were also found
  when oxiracetam was combined with the anticholinergic agent
  scopolamine. 5. On the whole, the above results demonstrate
  facilitation of active avoidance acquisition by piracetam-like
  nootropic agents, but the neurochemical mechanisms involved in this
  action are not yet clear.

Institutional address:
     Istituto di Psicobiologia e Psicofarmacologia

Gainotti G  Nocentini U  Sena E
Can the pattern of neuropsychological improvement obtained with
  cholinergic drugs be used to infer a cholinergic mechanism in other
  nootropic drugs?
Prog Neuropsychopharmacol Biol Psychiatry 1989;13 Suppl:S47-59

1. Enhancement of episodic memory and reduction of intrusion errors
  are considered as the most characteristic outcome of cholinergic
  drugs administration in AD patients. 2. Since the nootropic drugs
  Piracetam and Oxiracetam are deemed to act through a cholinergic
  mechanism, we checked whether AD patients treated with these drugs
  would show the same pattern of neuropsychological improvement. 3.
  Results were negative, since (a) episodic memory showed a similar
  degree of improvement both in patients treated with these drugs and
  in patients treated with placebo; (b) the number of intrusions tended
  to increase, rather than to decrease, after the treatment period.

Institutional address:
     Institute of Neurology
     2nd School of Medicine
     University of Naples

Kocur J  Rydzynski Z  Zujewski E  Kuzitowicz-Pabich A  Trendak W
[Effect of physostigmine and various nootropic drugs on various
  mental disorders caused by brain injury]
Wplyw fizostygminy i niektorych srodkow nootropowych na pozne
  zaburzenia psychiczne spowodowane urazem mozgu.
Psychiatr Pol 1988 Sep-Oct;22(5):317-21  (Published in Polish)

Wulfert E  Hanin I  Verloes R
Facilitation of calcium-dependent cholinergic function by ucb L059, a
  new "second generation" nootropic agent.
Psychopharmacol Bull 1989;25(3):498-502

We have investigated the effect of piracetam (PIR) and of its
  structural analogs, ucb L059 and ucb L060, the optical isomer of ucb
  L059, on cholinergic function in the guinea pig ileum in vitro. Only
  ucb L059 (10 microM-10 mM) caused contraction of the ileal
  preparation in a dose-dependent manner. This effect was inhibited by
  atropine (greater than or equal to 3.2 nM), by tetrodotoxin (10 nM)
  and by a combined treatment of veratridine (50 nM) and hemicholinium-
  3 (HC-3;0.5 mM), and was potentiated by physostigmine (50 nM).
  Electrically evoked contractions (EEC) of guinea pig ileal
  preparations subjected to HC-3 (0.5 mM) followed by veratridine (50
  microM) were suppressed due to depletion of acetylcholine. Choline
  (greater than or equal to 3.2 10(-7)M) and ucb L059 (0.1-10 mM), but
  not ucb L060, facilitated recovery of EEC in a dose-dependent manner.
  This effect was abolished by HC-3. In addition, twitch recovery was
  inversely related to the concentration of Ca+2 in the medium. These
  results indicate that ucb L059, a close structural analog of
  piracetam, appears to facilitate cholinergic function in vitro
  through a stereospecific mechanism.

Sara SJ
Memory retrieval deficits: alleviation by etiracetam, a nootropic
Psychopharmacology (Berlin) 1980;68(3):235-41

Etiracetam, a nonanaleptic drug related to the nootropic substance
  piracetam, was found to facilitate memory retrieval in rats in
  several experimental situations, when injected 30 min prior to
  retention testing. The drug was active when memory deficits were
  induced by electroconvulsive shock, undertraining, or by a long
  training-to-test interval. The behavioral paradigms included a one-
  trial inhibitory avoidance task and a complex multitrial, spatially
  discriminated approach task. The clinical interest of drugs which
  facilitate retrieval processes is also discussed.

Nicholson CD
Pharmacology of nootropics and metabolically active compounds in
  relation to their use in dementia.
Psychopharmacology (Berl) 1990;101(2):147-59

The development of effective drugs for the treatment of dementia is
  an important therapeutic target. Drugs which stop the progression of
  dementia have not been developed; however, nootropics and
  metabolically active compounds such as the vinca alkaloids and the
  ergot alkaloids as well as alkylxanthines are widely used to
  alleviate the symptoms. This review summarises animal studies
  investigating the mechanism of action of these compounds and
  highlights gaps in our knowledge of their pharmacology. Nootropics,
  such as piracetam, facilitate learning and retrieval of information
  and protect the brain from physical and chemical intoxication.
  Nootropics may produce these effects via an enhancement of
  acetylcholine or dopamine release; however, this postulate requires
  further evaluation. The pharmacology of vinca alkaloids is reviewed
  with particular reference to vinpocetine. This compound attenuates
  cognitive deficits, reduces ischaemia-induced hippocampal cell loss
  and increases cerebral blood flow and glucose utilisation. These
  effects may be induced by modulation of cyclic nucleotide levels and
  adenosine re-uptake inhibition. An extensively examined ergot
  alkaloid is co-dergocrine; this compound increases both the oxygen
  tension and the electrical activity of the ischaemic cerebral cortex.
  Alkylxanthines have a wide range of pharmacological activities, and
  in this review the pharmacology of pentoxifylline, propentofylline
  and denbufylline is contrasted with that of theophylline and
  caffeine. In particular, the pharmacology of propentofylline and the
  selective low Km cyclic AMP phosphodiesterase inhibitor denbufylline
  is summarised. Although more carefully controlled clinical trials in
  well defined patient collectives are required, present evidence
  suggests some therapeutic efficacy for nootropics and metabolically
  active compounds. Further studies to more closely evaluate their
  mechanism of action may lead to the development of more effective
  agents for the therapy of dementia.

Institutional address:
     Scientific Development Group
     Organon Laboratories Limited

ndadori C  Etienne P
Nootropic effects of ACE inhibitors in mice.
Psychopharmacology (Berl) 1990;100(3):301-7

The angiotensin converting enzyme (ACE) inhibitors captopril and
  enalapril and the nootropic piracetam reduced the amnesiogenic
  effects of cerebral electroshock treatment in mice. These compounds
  also directly improved passive-avoidance learning if administered
  before the learning trial. When given immediately after the learning
  trial, captopril and piracetam were active, but not enalapril.
  Captopril, but neither enalapril nor piracetam, facilitated memory
  retrieval after a 2-month retention interval. Unlike those of
  piracetam, the memory-improving effects of captopril and enalapril
  are not established by aldosterone-receptor blockade, suggesting that
  the two types of drug act via different mechanisms of action.

Institutional address:
     Pharmaceutical Research Department

Assessment of various psychopharmacological combinations in the
  treatment of presenile and senile primary degenerative dementia.
Rom J Neurol Psychiatry 1990 Oct-Dec;28(4):277-94

The effects of various psychopharmacological combinations were used
  in a sample of 90 patient fulfilling the DMS-III criteria for
  presenile or senile primary degenerative dementia divided into 3
  equal subgroups. Regardless of the drug combination used, an
  improvement of verbal test performances was noticed.

Institutional address:
     Institute of Neurology and Psychiatry

Karaseva TL  Tsapenko ZhN  Golovenko NIa  Timofeeva SE  Luk'ianenko NG
[Gamma-aminobutyric acid metabolism in the rat brain after
  administration of nootropic agents]
Obmen gamma-aminomaslianoi kisloty v golovnom mozge krys v usloviiakh
  vvedeniia im nootropnykh sredstv.
Vopr Med Khim 1988 May-Jun;34(3):81-4  (Published in Russian)

N,N-bis-pyrrolidonomethyl-diaza - 18-crown-6 and piracetam, which are
  structural analogues of gamma-aminobutyric acid (GABA) and exhibit
  nootropic properties, affected the GABA metabolism, the content of
  total protein, DNA and RNA in rat brain after long-term
  administration at pharmacologically active doses of 100 mg/kg and 400
  mg/kg, respectively. As compared with control values, content of GABA
  in rat brain was increased by 40% after administration of N,N-bis-
  pyrrolodonomethyl-diaza-18-crown-6 and by 28%--after treatment with
  piracetam. At the same time, activity of GABA transaminase was
  decreased by 49.4% and 39.8%, respectively, while the decarboxylase
  activity was unaltered.

Lekomtsev VT
[Nootropic agents in the complex treatment of patients with traumatic
Nootropy v kompleksnom lechenii bol'nykh travmaticheskoi epilepsiei.
Zh Nevropatol Psikhiatr 1990;90(6):68-72  (Published in Russian)

A study was made of the therapeutic efficacy of nootropic agents in
  multimodality treatment of 62 patients with traumatic epilepsy. The
  treatment efficacy was appraised with regard to the time-course of
  changes in psychopathological symptomatology. The data obtained have
  been processed statistically according to criteria for the signs.
  When applied in multimodality treatment of patients with traumatic
  epilepsy the nootropic agents turned out most efficacious for the
  psycho-organic syndrome and for the status of deranged consciousness.
  The use of the nootropic agents as part of rehabilitation therapy
  allows improvement of the secondary prophylaxis of traumatic

Niss AI
[Place of neurometabolic stimulators (cerebroprotectors) in the
  current systematics of psychotropic drugs and their principal kinds
  of clinical activity]
Mesto neirometabolicheskikh stimuliatorov (tserebroprotektorov) v
  sovremennoi sistematike psikhotropnykh sredstv i osnovnye vidy ikh
  klinicheskoi aktivnosti.
Zh Nevropatol Psikhiatr 1984;84(5):750-6  (Published in Russian)

The article deals with the modern concepts of the spectrum of the
  psycho- and neurotropic activity of neurometabolic stimulants, the
  correlation between the radicals of their clinical activity and the
  neurophysiological mechanism of their action. Comparative
  characteristics of some representatives of this series of agents are
  presented with emphasis on their specific position in the
  psychotropic drug systematics.

Turova NF  Ermolina LA  Baryshnikov VA  Kopaladze RA  Aziavchik AV
[Effect of nootropic agents on serum biochemical indices in
  intellectually deficient children]
O vliianii nootropov na biokhimicheskie pokazateli syvorotki krovi u
  detei s intellektual'noi nedostatochnost'iu.
Zh Nevropatol Psikhiatr 1983;83(10):1558-63  (Published in Russian)

It was shown that a marked therapeutic effect or its absence in the
  piracetam and nootropil treatment of children with different degrees
  of mental retardation is largely determined by the presence in
  patients' metabolism (before treatment) of certain combined changes
  in the general activity of lactate dehydrogenase (LDH) and its
  isoenzymic spectrum with regard to the ratio between aerobic and
  anaerobic subunits. Experimental studies on rats support the
  necessity of taking into account patients' metabolism when
  prescribing nootropic agents. It is suggested that considering LDH
  changes (along with the clinical condition of patients) may be of
  prognostic significance in the efficacy assessment of treatment with
  nootropic drugs.

Aleksandrovskii IuA  Bobkov IuG  Neznamov GG  Serebriakova TV  Boiko SS
[Use of the new psychotropic preparation bemitil in treating asthenic
  disorders (clinico-pharmacological research)]
Primenenie novogo psikhotropnogo preparata bemitila pri lechenii
  astenicheskikh narushenii (kliniko-farmakologicheskoe issledovanie).
Zh Nevropatol Psikhiatr 1988;88(3):109-15  (Published in Russian)

In a series of 130 patients with asthenic conditions related to
  borderline forms of neuro-mental disturbances the authors compared
  clinico-pharmacological action of the actoprotector bemitil with that
  of nootropic drugs (piracetam and piridotol). The treatment with
  bemitil was either continuous or intermittent, being conducted
  according to the scheme elaborated in the course of the study.
  Bemitil proved to be more effective than piracetam and piriditol in
  relation to its influence on the manifestations of the asthenic
  symptom complex in general. Its application was characterized by a
  faster onset of the therapeutic effect and a peculiar mild
  psychostimulating action, primarily manifested in the impact on
  obligate manifestations of the asthenic disorders. The degree of the
  psychotropic action of the drug was found to be subject to changes
  depending on the scheme of its use.

Niss AI  Trubkovich MIa
[Various rarely encountered adverse effects and complications of
O nekotorykh redko vstrechaiushchikhsia pobochnykh effektakh i
  oslozhneniiakh psikhofarmakoterapii.
Zh Nevropatol Psikhiatr 1985;85(5):755-60  (Published in Russian)

Nine patients are described in whom psychopharmacotherapy was
  associated with the development of rare complications in the form of
  the syndrome of cortical disturbances, psychosensory disorders and
  toxic polyneuropathy. All patients presented residual organic
  insufficiency of the CNS, with some of them exhibiting endocrine-
  metabolic disorders as well.

Madorskii SV  Potapov AA  Piasetskaia MV  Shapova EV  Il'icheva RF
[Effect of nootropic agents on the brain bioelectrical activity and
  on the indices of neuromediator metabolism in the acute period of
  severe craniocerebral trauma]
Vliianie nootropov na bioelektricheskuiu aktivnost' mozga i
  pokazateli neiromediatornogo obmena v ostrom periode tiazheloi
  cherepno-mozgovoi travmy.
Zh Vopr Neirokhir 1989 May-Jun(3):29-35  (Published in Russian)

Clinico-biochemical examination and EEG were conducted in 39 patients
  with severe craniocerebral trauma who were given nootropic agents in
  a complex of intensive therapy measures. Four types of changes of
  monoamine metabolism in treatment with piracetam were revealed which
  were combined with two types of EEG changes. The authors recommend
  the time for beginning piracetam therapy depending on the level of
  traumatic injury to the brain.

Inozemtsev AN  Pragina LL
[A reversible disorder of the avoidance reaction as an experimental
  model for the study of the action of psychotropic preparations on
  higher nervous activity]
Obratimoe narushenie reaktsii izbeganiia kak eksperimental'naia
  model' izucheniia deistviia psikhotropnykh preparatov na vysshuiu
  nervnuiu deiatel'nost'.
Zh Vyssh Nerv Deiat 1989 Jul-Aug;39(4):764-6  (Published in Russian)

Markina NV  Nerobkova LN  Voronina TA
[Effect of drugs of the nootropic class on rat behavior after
  deprivation of the paradoxical stage of sleep]
Vliianie veshchestv klassa nootropov na povedenie krys v usloviiakh
  deprivatsii paradoksal'noi fazy sna.
Zh Vyssh Nerv Deiat 1986 Sep-Oct;36(5):963-7  (Published in Russian)

Pharmacological analysis was used for studying the influence of 24-
  hour deprivation of paradoxical sleep by Jouvet method on retention
  of conditioned reaction of passive avoidance in rats. Psychotropic
  substances of different action were used for the analysis: nootropes
  as anti-amnestic--pyracetam (400 mg/kg), kleregil (100 mg/kg),
  centrofenoxin (50 mg/kg) and watersoluble salt of 3-oxypiridin
  derivative (3-OP) (50 mg/kg) and tranquilizer of bensodiazepine
  series phenazepam (1 mg/kg) as antistress and antiphobic. It was
  established that 24-hour deprivation disturbed the elaborated
  reaction but did not change the rate of emotionality and orienting-
  investigating behaviour of rats in the open field. Nootropes
  effectively restored the conditioned passive avoidance reaction while
  phenazepam had no effect. This allows to suggest that Jouvet method
  of paradoxical sleep deprivation elicits amnesia and its cause is not
  only stress but deficit of paradoxical sleep.

		"And you thought I never went away" - X