A Novel Cognitive Enhancing Substance GVS-111

Abstract

Design of piracetam peptide analogues was proposed as a new approach to the creation of cognitive enchancers (Gudasheva et al, 1985). Dipeptides containing pyroglutamic acid with various natural amino acids were shown to be able to restore cognition damaged by a number of noxious influences in doses 0.001-1.0 mg/kg (Ostrovskaya et al, 1987, Gudasheva et al, 1988). Recently we showed antiamnestic effects in acyl prolyl containing dipeptides, in particular in phenylacetylprolyl derivatives. GVS-111 was chosen as one of the most active substances of this series. It was studied in the passive avoidance paradigm in rats. The substance was demonstrated to be able to facilitate acquisition per se. Administered before testing it facilitated retrieval processes as well. GVS-111 attenuated the amnestic effect of electroshock, scopolamine & proline cethylester (lypophylic prodrug of proline, designed by Skoldinov et al.). GVS-111 increased the degree of acute habituation of exploratory behavior in grouped (n= 10) mice without effect on baseline locomotion. GVS-111 showed all above listed mnemotropic effects in doses 0,1-1.0 mg/kg (i.p),LD 50 for mice is 5000 mg/kg. GVS-111 possesses much higher biological stability than TRH & AVP.GVS-111 preserved effectiveness in peroral administration. These studies demonstrate that GVS-111 may encance memory under range of condition.