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

TY - JOUR

T1 - The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys

AU - Brandt-Christensen, M

AU - Andersen, M B

AU - Fink-Jensen, A

AU - Werge, T

AU - Gerlach, J

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

U2 - http://dx.doi.org/10.1007/s00702-005-0297-1

DO - http://dx.doi.org/10.1007/s00702-005-0297-1

M3 - Journal article

SN - 0375-9245

VL - 113

SP - 11

EP - 19

JO - Acta Neurovegetativa

JF - Acta Neurovegetativa

IS - 1

ER -