title: The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys.
abstract: Low affinity dopamine (DA) D2 antagonists such as the substituted (S)-3-phenylpiperidine (-)-OSU6162 have been proposed to be putative antipsychotic agents not endowed with extrapyramidal side effects (EPS). In the present study we investigated the effects of (-)-OSU6162 on (-)-apomorphine and d-amphetamine-induced behaviours in EPS sensitised Cebus apella monkeys. (-)-OSU6162 was administered subcutaneously in doses of 1, 3, 6 and 9 mg/kg alone and in combination with (-)-apomorphine (0.25 mg/kg) or d-amphetamine (0.5 mg/kg). (-)-OSU6162 inhibited (-)-apomorphine-(1-9 mg/kg) as well as d-amphetamine (3-9 mg/kg)-induced arousal and stereotypy. EPS did not occur when (-)-OSU6162 was administered in combination with (-)-apomorphine or d-amphetamine. However, when (-)-OSU6162 was administered alone, dystonia was observed at high doses (6 and 9 mg/kg) in two out of six monkeys. The present study shows that (-)-OSU6162 can inhibit (-)-apomorphine-induced behaviours in non-human primates at doses that do not cause EPS. When (-)-OSU6162 was tested against d-amphetamine-induced behaviours a separation between dose levels that inhibit d-amphetamine effects and cause EPS was not observed. The data further substantiate a role for low affinity DA D2 antagonists in the pharmacological treatment of psychosis.
authors.affiliation: Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Brandt-Christensen
authors.forename: M B
authors.initials: MB
authors.lastname: Andersen
authors.forename: A
authors.initials: A
authors.lastname: Fink-Jensen
authors.forename: T
authors.initials: T
authors.lastname: Werge
authors.forename: J
authors.initials: J
authors.lastname: Gerlach
mesh_terms: D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002428:Cebus; D004305:Dose-Response Relationship, Drug; D008297:Male; D010880:Piperidines / Q000737:chemistry / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000502:physiology
chemical_list: D010880:Piperidines; C109513:OSU 6162; D000661:Amphetamine; D001058:Apomorphine