Amnesia associated with electroconvulsive therapy: Progress in pharmacological prevention and treatment
Pollina D.A.; Calev A.
Dr. D.A. Pollina, Department of Neurology, HSC T12-020, State University of New York, Stony Brook, NY 11794-8121 USA
CNS Drugs (New Zealand), 1997, 7/5 (381-387)

Pharmacological treatments have been used in an attempt to improve the memory dysfunction induced by electroconvulsive therapy (ECT). Despite promising results from animal studies, human studies report few successes. Piracetam and physostigmine have been reported to directly improve memory test scores. The use of caffeine and liothyronine (triiodothyronine; T3) has been reported to reduce the number of ECT treatments required to produce a therapeutic effect, thus indirectly reducing memory deficits. However, the majority of studies on pharmacological treatments report no success. Some studies suggest that reducing the dosage of medications regularly administered with ECT may reduce memory deficits. However, reducing these medications may not be fruitful as they are necessary to prevent the medical risks associated with ECT. Moreover, at the dosages used during ECT, these medications have not been consistently shown to adversely affect cognition. At present, better controlled studies are required to assist in the search for effective pharmaceutical agents to reduce the cognitive deficits associated with ECT.

Piracetam and fipexide prevent PTZ-kindling-provoked amnesia in rats
Genkova-Papazova M.G.; Lazarova-Bakarova M.B.
M.G. Genkova-Papazova, Dept. of Experimental Pharmacology, Institute of Physiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. bl. 23, 1113 Sofia Bulgaria
European Neuropsychopharmacology (Netherlands), 1996, 6/4 (285-290)

Deficit in active and inhibitory avoidance behaviour has been found in pentylenetetrazole (PTZ)-kindled rats. This supports the view that memory deficit is an integral part of epilepsy. In the present study we examined the effect of the nootropic drugs piracetam and fipexide on memory deficit induced by PTZ-kindling in shuttle-box- and step-down-trained rats. The retention in piracetam- and fipexide-treated animals was significantly improved compared to the kindled controls. The mechanisms of action of the two drugs are considered. The favourable effects of nootropic drugs in cases of amnesia provoked by PTZ-kindling might be of interest in clinical practice.

p-Hydroxybenzyl alcohol attenuates learning deficits in the inhibitory avoidance task: Involvement of serotonergic and dopaminergic systems
Wu C.-R.; Hsieh M.-T.; Liao J.
Chinese Journal of Physiology (Taiwan), 1996, 39/4 (265-273)

p-Hydroxybenzyl alcohol (HBA), an aglycone of gastrodin, is an active ingredient of Gastrodia elata B(LUME). In this study, we investigated the action of HBA on acquisition of an inhibitory avoidance response in rats and used piracetam as a positive control. The results indicated that scopolamine, a cholinergic receptor antagonist, injected before training impaired retention. HBA did not attenuate the scopolamine-induced impairment, but piracetam did. p-Chloroamphetamine, a serotonin releaser, injected before training impaired retention. HBA at 5 mg/kg and piracetam at 100 mg/kg could counteract the p-chloroamphetamine-induced deficit. Apomorphine, a dopaminergic receptor agonist, also impaired retention. HBA at 5 mg/kg and piracetam at 300 mg/kg could ameliorate the apomorphine-induced amnesia. The above results indicated that HBA, different from piracetam, can attenuate impairments induced by p-chloroamphetamine and apomorphine, but had no effect on impairment induced by scopolamine in an inhibitory avoidance task in rats. Such findings suggest that HBA may act through suppressing dopaminergic and serotonergic activities and thus improves learning.

Comparative review of the adverse effects of sedatives used in children undergoing outpatient procedures
D'Agostino J.; Terndrup T.E.
Department of Emergency Medicine, State University, New York Health Science Center, 750 E Adams Street, Syracuse, NY 13210 USA
Drug Safety (New Zealand), 1996, 14/3 (146-157)

Children often fear medical procedures and interventions. Sedative agents enhance the care of these children who undergo outpatient procedures by decreasing anxiety, increasing cooperativity, and providing amnesia, although higher dosages and intravenous administration of sedatives often produce improved sedation, adverse effects and complications are more frequent. The goals of therapeutic efficacy and safety must be balanced in all patients. The presence or anticipation of anxiety and pain helps in deciding whether to use a sedative alone, or a regimen also providing analgesia. The patient's clinical cardiorespiratory or neurological status, other relative contraindications, the duration of the intended procedure, and the presence or absence of an intravenous line will help in choosing specific drugs. Drug complications are a common cause of adverse events in patients. The combination of a sedative and analgesic, especially a benzodiazepine and an opioid given intravenously, is associated with a higher risk of serious complications. The practitioner responsible for the administration of a sedative to a child must be competent in its use and have the ability to detect and manage complications. Patients who are deeply sedated should be continuously monitored and observed by an individual dedicated to this task. Vital signs and oxygen saturation should be documented at frequent intervals and the patient should be appropriately monitored until discharge criteria have been met. The risk of serious complications with these agents may be reduced with vigorous monitoring and a judicious choice of dosage.

Antagonism of piracetam with proline in relation to amnestic effects
Ostrovskaia RU; Trofimov SS; Tsybina NM; Gudasheva TA; Skoldinov AP
Biull Eksp Biol Med (USSR) Mar 1985, 99 (3) p311-4

Based on the authors' previous data showing that the lipophylic cethyl group promotes the penetration of amino acids through the blood-brain barrier, proline cethyl ester was synthesized and studied as a neuropharmacological tool. The substance administered to rats systemically (intraperitoneally) was shown to be able to provoke a deep amnesia when tested by the conditioned avoidance performance. Piracetam abolished the amnestic effect of proline cethyl ester while sodium hydroxybutyrate administered in the dosage range provoking the nootropic effect did not change that amnesia. The data suggest that proline may be considered as one of the possible endogenous amnestic factors. The close structural similarity of the piracetam cyclic fragment to proline, which resulted in their competition, appears to be one of the reasons for piracetam antiamnestic activity.

Effect of mental stimulants on electroconvulsive shock-induced retrograde amnesia
Hoffmann W; Rostock A
Pharmazie (Germany, East) Dec 1983, 38 (12) p869-71

The effect of nootropics on the retrograde amnesia induced by electroshock was studied on a model of the active conditioned escape reaction (pole jumping). In untreated animals the daily application of electroshock for three days, immediately after the training, led to a significant retardation of the development of a conditioned escape reaction. The administration of nootropics influences the development of the retrograde amnesia to different extents, the treatment regimen (application of the drug only during the training and supplementary pretreatment before the first day of training; respectively) being of importance. The antiamnestic effect of Piracetam (100 mg/kg, intraperitoneally) which is good also without pretreatment, may still be potentiated, especially on the fourth day of treatment, by an additional administration of the drug, beginning four days before the first day of treatment. In contrast to this, meclofenoxate hydrochloride (100 mg/kg, intraperitoneally) and pyritinol (100 mg/kg, intraperitoneally) produce a marked inhibition of the development of the retrograde amnesia only after pretreatment. Without pretreatment these drugs exert a slight or no effect. The marked antiamnestic effect of methylglucaminorotate (225 mg/kg, intraperitoneally) and by an additional pretreatment. As to dihydroergotoxin (1 mg/kg; intraperitoneally), both treatment regimens were ineffective in the model used.

Hypoxia-induced amnesia in one-trial learning and pharmacological protection by piracetam.
Sara SJ; Lefevre D
Psychopharmacologia (Germany, West) 1972, 25 (1) p32-40

No abstract.

Pre-clinical evaluation of cognition enhancing drugs.
Schindler U
Department of CNS Pharmacology, Cassella AG, Frankfurt, Federal Republic of Germany.
Prog Neuropsychopharmacol Biol Psychiatry (England) 1989, 13 Suppl pS99-115

1. The need of the treatment of cognitive impairment due to aging or dementia has led to the search for potential cognition enhancing drugs. The various compounds presently under development represent an alternative tothe cholinomimetic therapy and include new chemical entities as well as piracetam and its newer analogs.

2. Recent results from pre-clinical evaluation of the effects on learning on memory are summarized. Emphasis is put on learning and memory experiments under normal and pathological conditions. Most of the nootropics attenuate experimental amnesias induced by scopolamine, cycloheximide, ECS, hemicholinium-3 or forebrain ischemia. These findings suggest that the nootropics may be influencing a common mechanism underlying the amnesias.

3. Biochemical data suggest a potential cholinergic neuronal activity of some of the piracetam analogs. They increase high-affinity choline uptake, and antagonize scopolamine and ECS-induced decreases in acetylcholine concentrations in the hippocampus. The mode of action of these and all other nootropic compounds, however, is still not known. 4. Despite the interesting results from learning and memory studies and from biochemical investigations, the clinical relevance of these results for amelioration of the cognitive impairment in humans remains to be proven for most of the compounds. (51 Refs.)

Nootropic drugs and brain cholinergic mechanisms.
Pepeu G; Spignoli G
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Prog Neuropsychopharmacol Biol Psychiatry (England) 1989, 13 Suppl pS77-88

1. This review has two aims: first, to marshal and discuss evidences demonstrating an interaction between nootropic drugs and brain cholinergic mechanisms; second, to define the relationship between the effects on cholinergic mechanisms and the cognitive process.

2. Direct or indirect evidences indicating an activation of cholinergic mechanisms exist for pyrrolidinone derivatives including piracetam, oxiracetam, aniracetam, pyroglutamic acid, tenilsetam and pramiracetam and for miscellaneous chemical structures such as vinpocetine, naloxone, ebiratide and phosphatidylserine. All these drugs prevent or revert scopolamine-induced disruption of several learning and memory paradigms in animal and man.

3. Some of the pyrrolidinone derivatives also prevent amnesia associated with inhibition of acetylcholine synthesis brought about by hemicholinium. Oxiracetam prevents the decrease in brain acetylcholine and amnesia caused by electroconvulsive shock. Oxiracetam, aniracetam and pyroglutamic acid prevent brain acetylcholine decrease and amnesia induced by scopolamine. Comparable bell-shaped dose-effect relationships result for both actions. Phosphatidylserine restores acetylcholine synthesis and conditioned responses in aging rats.

4. The mechanisms through which the action on cholinergic systems might take place, including stimulation of the high affinity choline uptake, are discussed. The information available are not yet sufficient to define at which steps of the cognitive process the action on cholinergic system plays a role and which are the influences of the changes in cholinergic function on other neurochemical mechanisms of learning and memory. (60 Refs.)

Specificity of piracetam's anti-amnesic activity in three models of amnesia in the mouse.
Lenegre A; Chermat R; Avril I; Steru L; Porsolt RD
I.T.E.M.-Labo, Kremlin-Bicetre, France.
Pharmacol Biochem Behav (United States) Mar 1988, 29 (3) p625-9

The effects of piracetam on the amnesias induced by scopolamine, diazepam and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse and compared with the interactions of piracetam with the major behavioral effects of these treatments, namely scopolamine-induced hyperactivity, diazepam-induced release of punished behavior (Four Plates Test) and ECS-induced convulsions. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg, IP) 30 minutes before or applying ECS immediately after the first session (S1) of the passive avoidance task. Piracetam was studied at 3 doses (512, 1024 and 2048 mg/kg) administered PO 60 minutes before S1. Retention was measured 24 hours later (S2) in the absence of any treatment. Piracetam dose-dependently attenuated the memory deficits induced by the three amnesic treatments but did not affect either scopolamine-induced hyperactivity, diazepam-induced release of punished behavior or ECS-induced convulsions. These results point to the specificity of piracetam's anti-amnesic activity and, in particular, suggest that piracetam can suppress the memory disturbances induced by diazepam without affecting diazepam's anxiolytic activity. The test battery employed would therefore seem highly suitable for evaluating the potential nootropic activity of novel compounds.

[Effects of piracetam during prolonged use in an experiment]
Rakhmankulova IKh; Garibova TL; Voronin KE; Tilekeeva UM; Voronina TA
Farmakol Toksikol (USSR) Jul-Aug 1985, 48 (4) p42-6

The spectrum of the pharmacological activity of piracetam administered for a long time was studied in experiments on mice and rats. It was established that administration of piracetam (300-400 mg/kg i. p.) for 10-42 days brought about potentiation of its antiamnestic effect, retardation of the processes of extinction, an increase in the emotional responsiveness, and preservation of the tranquilizing effect with no side effects (sedative or myorelaxant). The characteristic feature of piracetam effect on the extinction is its ability to decelerate this process only after its prolonged administration. It is assumed that under prolonged administration of piracetam there takes place the formation of a new functional system ensuring the memory trace stabilization.

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