Atypical antipsychotic-like effects of the dopamine D3 receptor agonist, (+)-PD 128,907.
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.
Witkin
J
J
Drug Development Group, NIDA Addiction Research Center, NIH, Baltimore, MD 21224, USA. jwitkin@irp.nida.nih.gov
Gasior
M
M
Acri
J
J
Beekman
M
M
Thurkauf
A
A
Yuan
J
J
DeBoer
P
P
Wikström
H
H
Dijkstra
D
D
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D051379:Mice; D010078:Oxazines / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D013239:Stereotyped Behavior / Q000187:drug effects
D014150:Antipsychotic Agents; D001578:Benzopyrans; D018491:Dopamine Agonists; C493594:Drd3 protein, mouse; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol