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

J Neural Transm (Vienna). 2006 Jan;113(1):11-9. doi: 10.1007/s00702-005-0297-1. Epub 2005 Mar 30.

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.

Publication types

  • Comparative Study

MeSH terms

  • Amphetamine / antagonists & inhibitors
  • Amphetamine / pharmacology*
  • Animals
  • Apomorphine / antagonists & inhibitors
  • Apomorphine / pharmacology*
  • Cebus
  • Dose-Response Relationship, Drug
  • Male
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Stereotyped Behavior / drug effects*
  • Stereotyped Behavior / physiology

Substances

  • Piperidines
  • OSU 6162
  • Amphetamine
  • Apomorphine