[Behavioral pharmacological investigation and clinical consideration of the inhibitory potencies of psychotropic drugs against the D-1 and D-2 dopamine receptors].
The potencies of various psychotropic drugs to antagonize stereotypes induced by a high dose of (-)-apomorphine (10 mg/kg) in rats have been investigated in a comparison with their inhibitory potencies against the D-1 and D-2 dopamine receptors binding sites in rat striatum labelled by 3H-cis-flupentixol and 3H-spiperone, respectively. cis-Flupentixol and fluphenazine, which had high affinities for D-1, showed about 10 times stronger inhibitory effects on the stereotypes than perphenazine and haloperidol, which had moderate or weak affinities for D-1, although these drugs had similar affinities for D-2. A D-1 selective antagonist, SCH 23390, showed manifest inhibitory effect. The D-2 selective antagonists tested, spiperone and YM-09151-2, also showed marked inhibitory effects on the stereotypes but their potencies were largely weakened by concomitant treatment with scopolamine (more than 20 times), whereas the potency of D-1 selective antagonist, SCH 23390, was little affected. Stereotypes induced by a high dose of (-)-apomorphine in rats may partly be mediated through D-1. Clinically, it is well known that D-2 antagonists are effective for the acute psychotic state, but not for the negative symptoms of chronic schizophrenia. On the basis of these laboratory and clinical findings, the possible roles of the D-1 receptor blocking property of some neuroleptic agents were discussed in terms of their clinical relevance.
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000032:analysis / Q000187:drug effects*; D008297:Male; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012559:Schizophrenia / Q000188:drug therapy; D013239:Stereotyped Behavior / Q000187:drug effects*
D011619:Psychotropic Drugs; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001058:Apomorphine