title: Comparison of antipsychotic activity and discriminative stimulus effects of the novel acylprolyltyrosine containing compound, GZR-123, and sulpiride.
abstract: 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 i.p.. 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 i.p. 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.
authors.affiliation: Institute of Pharmacology of RAMS, Moscow, Russia.
authors.forename: L S
authors.initials: LS
authors.lastname: Asmakova
authors.forename: T S
authors.initials: TS
authors.lastname: Kalinina
authors.forename: R U
authors.initials: RU
authors.lastname: Ostrovskaya
authors.forename: T A
authors.initials: TA
authors.lastname: Gudasheva
authors.forename: N I
authors.initials: NI
authors.lastname: Zaitseva
authors.forename: N A
authors.initials: NA
authors.lastname: Bondarenko
authors.forename: T A
authors.initials: TA
authors.lastname: Voronina
authors.forename: S B
authors.initials: SB
authors.lastname: Seredenin
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced; D004192:Discrimination, Psychological / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D015259:Dopamine Agents; D018491:Dopamine Agonists; C401484:GZR 123; D014443:Tyrosine; D007980:Levodopa; D013469:Sulpiride; D011392:Proline; D001058:Apomorphine