Pharmacological effects of a specific dopamine D-1 antagonist SCH 23390 in comparison with neuroleptics.
Neuroleptics such as thioxanthenes (cis(Z)-flupentixol and cis(Z)-clopenthixol) and phenothiazines (fluphenazine and perphenazine), which block both dopamine (DA) D-1 and D-2 receptors and the butyrophenones (haloperidol and spiroperidol), which block D-2 receptors only, are equipotent both behaviorally and clinically. A new compound SCH 23390 which selectively blocks DA D-1 receptors, resembles many neuroleptics in its pharmacological profile: antistereotypic effects in mice, rats and dogs, cataleptogenic effect and inhibitory effect on amphetamine circling. In contrast SCH 23390 has no effect on apomorphine-induced vomiting in dogs and little effects on 6-OHDA-denervated supersensitive DA receptors, stimulated by the DA agonist 3-PPP. In a series of experiments where methylphenidate-induced stereotyped gnawing in mice was inhibited by neuroleptics, it was shown that concomitant treatment with scopolamine or diazepam attenuated the effect of butyrophenones (D-2 antagonists). The same treatment attenuated the effect of phenothiazines, to a lesser extent, and hardly attenuated the effect of thioxanthenes and SCH 23390 at all. It is concluded that DA D-1 receptors are as important as D-2 receptors for the expression of neuroleptic activity in most animal models believed to be predictive of antipsychotic and extrapyramidal side-effect potential. However, the D-1 antagonist is less sensitive than D-2 antagonists to antimuscarinic compounds and benzodiazepines.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D000932:Antiemetics; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D004285:Dogs; D018492:Dopamine Antagonists; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists; D006801:Humans; D008297:Male; D051379:Mice; D010276:Parasympatholytics; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1
D000317:Adrenergic alpha-Antagonists; D000932:Antiemetics; D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D006634:Histamine H1 Antagonists; D010276:Parasympatholytics; D017447:Receptors, Dopamine D1