P.4.004 Dipeptide anxiolytic GB-115: new receptor targets

Abstract

ASMAKOVA L. S., T. S. KALININA, R. U. OSTROVSKAYA, T. A. GUDASHEVA, N. I. ZAITSEVA,N. A. BONDARENKO, T. A. VORONONA, AND S. B. SEREDENIN. Comparison of antipsychotic activity and discriminative stimulus effects of the novel acylprolyltyrosine containing compound, GZR-123, and Sulpiriride. PHARMACOL BIOCHEM BEHAV 64(2) 359–362, 1999.—The present experiment has been performed to determine the pharmacological profile of a newly synthesized systematically active prolyltyrosine containing compound, caproyl-L-Pro-L-Tyr methyl ester (GZR-123), and to compare it with that of the standard atypical benzamide neuroleptic, sulpiride. GZR-123 demonstrated antagonistic activity on apomorphine-induced climbing and on l-DOPA–dependent extrapolatory behavior in dose ranging between 0.4–4.0 mg/kg IP. It did not provoke a cataleptogenic effect or lethality, even at doses much higher than those causing antidopamine effects (more than 500 mg/kg). The effective doses of sulpiride in the above-listed antidopamine tests were shown to be 17.5 and 16.0 mg/kg IP correspondingly. Although these doses of sulpiride did not demonstrate cataleptogenic effects, an increase of the dose level to 120 mg/kg induced pronounced catalepsy. Both GZR-123 (6 mg/kg) and sulpiride (40 and 60 mg/kg) were investigated by training rats to discriminate each of them from saline in a two-lever, water-reinforcement operant procedure. Both GZR-123 and sulpiride demonstrated weak discriminability in this task. GZR-123 increased drug-associated lever selection when administered in doses of 2 and 6 mg/kg, for sulpirirde these doses were demonstrated to be 25–60 mg/kg. In contrast to GZR-123, which did not provoke a sedative effect, sulpiride in higher discriminable doses caused sedation, which stems probably from the motivational, but not from the motor deficit.