The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys
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The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys. / Brandt-Christensen, M; Andersen, M B; Fink-Jensen, A; Werge, T; Gerlach, J.
In: Journal of Neural Transmission, Vol. 113, No. 1, 2006, p. 11-9.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 113
SP - 11
EP - 19
JO - Acta Neurovegetativa
JF - Acta Neurovegetativa
SN - 0375-9245
IS - 1
ER -
ID: 48447774