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Atypical antipsychotic-like effects of the dopamine D3 receptor agonist, (+)-PD 128,907. 1998
J Witkin, and
M Gasior, and
J Acri, and
M Beekman, and
A Thurkauf, and
J Yuan, and
P DeBoer, and
H Wikström, and
D Dijkstra
Drug Development Group, NIDA Addiction Research Center, NIH, Baltimore, MD 21224, USA. jwitkin@irp.nida.nih.gov
Anti-schizophrenia agents with improved efficacy and side-effect profiles are required. A dopamine D3 receptor agonist, R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3- b]-1,4-oxazin-9-ol HCl ((+)-PD 128,907), displayed an atypical antipsychotic profile comparable to that of clozapine. (+)-PD 128,907 blocked stereotypy produced by dizocilpine (MK-801) at 12-fold lower doses than those affecting apomorphine-induced stereotypes in mice and did not produce catalepsy. These effects of (+)-PD 128,907 were stereospecific and were blocked by a D3 antagonist. These data suggest a role for D3 receptors in antipsychotic drug action.
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