[Behavioral and electrophysiological analysis of the choline-positive effect of nootropic dipeptide acylproline (GVS-111)].
The behavioral experiments using a passive avoidance learning model showed that the new cognition-enhancing acyl-prolyn containing dipeptide GVS-111 promotes recovery of the test performance in animals with a long-term memory deficit caused by the M-cholinolytic scopolamine (1 mg/kg/day scopolamine for 20 days, followed by 0.5 mg/kg/day GVS-111 for 10 days). At the same time, GVS-111 increased the duration of tremor induced by the M-cholinomimetic arecoline. The results of electrophysicological experiments showed that GVS-111 in a concentration range from 10(-11) to 10(-9) M increased amplitude of the neural response to acetylcholine (Ach) microappications in 75% of the isolated neurons of Helix Pomatum and produced a predominantly facilitating effect upon the endoneuronal pacemaker activity. The effect of GVS-111 upon the Ach response in a part of neurons was attenuated or even blocked by scopolamine, and in the other neurons--by the N-cholinolytic d-tubocurarine. This fact indicates that both muscarinic and nicotinic receptors are involved in the mechanism of the cholino-sensitizing action of GVS-111 upon the neuronal activity.
Ostrovskaia
R U
RU
Laboratory of Psychopharmacology, Institute of Pharmacology, Russian Academy of Medical Sciences, Baltiiskaya ul. 8, Moscow, 125315 Russia.
Mirzoev
T Kh
TKh
Firova
F A
FA
Trofimof
S S
SS
Gudasheva
T A
TA
Grechenko
T N
TN
Gutyrchik
E F
EF
Barkova
E B
EB
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology*; D004594:Electrophysiology; D017952:Ganglia, Invertebrate / Q000166:cytology; D006372:Helix, Snails; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
D004151:Dipeptides; D018727:Muscarinic Antagonists; D018697:Nootropic Agents; C103871:ethyl phenylacetyl-Pro-Gly; D012601:Scopolamine; D000109:Acetylcholine