The substituted (S)-3-phenylpiperidine (−)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys

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.