ABSTRACT
In experimental studies on mice it was shown that piracetam, Cleregil, centrophenoxine, pyritinol possessed the most pronounced anti-amnestic activity. A close effect was noted with Euclidan, 3-hydroxypyridine and ionol. GABAergic agents (sodium oxybutyrate, phenibut, pantogam), gutimine, nicotinoyl-GABA eliminated amnesia to a lesser extent. The antihypoxic effect on the model of hypobaric hypoxia was exerted by typical antihypoxic agents (gutimine, sodium oxybutyrate, 3-hydroxypyridine). The antihypoxic activity of nootropic drugs (centrophenoxine, pyritinol, phenibut) could be determined only at a significant increase of doses. No interrelationship and the presence of dissociation in manifestation of anti-amnestic and antihypoxic effects were revealed.
Subject(s)
Amnesia/drug therapy , Antioxidants/therapeutic use , Hypoxia/drug therapy , Psychotropic Drugs/therapeutic use , Animals , Conditioning, Classical/drug effects , Drug Evaluation, Preclinical , Electroshock , Escape Reaction/drug effects , Male , Mice , Structure-Activity RelationshipABSTRACT
It was found during experiments using three models of hypoxia (hypobaric, normobaric, hemic) in mice that derivatives of 3-hydroxypyridine possess an antihypoxic effect. They are as active as sodium hydroxybutyrate but less active than gutimine. A clear-cut dependence of the antihypoxic activity on the radical character in the 2nd position of 3 hydroxypyridine was revealed. The presence of a hydroxy group in the 3rd position of pyridine ring was shown to be very important for the antihypoxic properties. The data suggesting different degrees of involvement of GABA and benzodiazepine receptors in realization of the antihypoxic effect were obtained.
Subject(s)
Antioxidants/therapeutic use , Hypoxia/drug therapy , Pyridines/therapeutic use , Acute Disease , Animals , Drug Evaluation, Preclinical , Hypercapnia/drug therapy , Hypercapnia/mortality , Hypoxia/mortality , Male , Mice , Structure-Activity RelationshipABSTRACT
It was revealed in experiments on mice, that 3-hydroxypyridine derivatives possess marked anticonvulsive activity, especially in convulsions induced by GABA-ergic substances, less in corasol, maximal electroshock and strychnine induced ones. The anticonvulsive activity in the rows of 2-substituted and 2.6-disubstituted derivatives of 3-hydroxypyridine gets increased due to the introduction of larger in volume alkyl substitutes into the 2nd molecule position. Among the 2,6-disubstituted 3-hydroxypyridine derivatives, agents were revealed that are able to enhance hyperkinesis induced by 5-hydroxytryptophan.
Subject(s)
Anticonvulsants/pharmacology , Pyridines/pharmacology , Animals , Anticonvulsants/therapeutic use , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Electroshock , Male , Mice , Pentylenetetrazole/antagonists & inhibitors , Pyridines/therapeutic use , Seizures/chemically induced , Seizures/drug therapy , Structure-Activity RelationshipABSTRACT
The experiments on rats, using conflict situation method, have established that anxiolytic effect of 3-hydroxypyridine derivative is removed by bicucullin and picrotoxin, but not by Ro 5-3663, specific antagonist of benzodiazepine receptors Ro 15-1788 and inversive antagonist ethyl beta-carboline-3-carboxylate. The data obtained suggest that GABA-chloriontophor complex is involved into the realization of 3-hydroxypyridine anxiolytic effect.
Subject(s)
Anti-Anxiety Agents , Antidepressive Agents/pharmacology , Pyridines/pharmacology , Receptors, GABA-A/physiology , Animals , Drug Interactions , Male , Rats , Receptors, GABA-A/drug effectsABSTRACT
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.
Subject(s)
Piracetam/pharmacology , Pyrrolidinones/pharmacology , Amnesia/drug therapy , Animals , Conditioning, Classical/drug effects , Conflict, Psychological , Emotions/drug effects , Escape Reaction/drug effects , Extinction, Psychological/drug effects , Learning/drug effects , Male , Memory/drug effects , Mice , Rats , Time FactorsABSTRACT
Experiments on mice and rats were made to study the effect of inhibitors-antioxidants (3-hydroxypyridine derivatives) on the central nervous system. It was established that 3-hydroxypyridine derivatives (50 to 200 mg/kg) possess a broad spectrum of psychotropic effects. They cause normalization of behavior in conflict situations, exert an antiaggressive and anticonvulsant action (antagonism with corazol), are capable of potentiating the hypnotic effect of barbiturates, and of suppressing the animals' motor activity if given in high doses. Most compounds under study have antihypoxic and antiamnestic effects.