Remoxipride, a new selective D2 antagonist, and haloperidol in cebus monkeys.
1. Nine Cebus monkeys, 6 with mild spontaneous oral dyskinesia (tongue protrusions), were tested with two dopamine D2 antagonists, remoxipride (a new substituted benzamide) and haloperidol, and with two dopamine agonists, methylphenidate and apomorphine. 2. Remoxipride 4 and 8 mg/kg and haloperidol 0.01 and 0.02 mg/kg given alone induced identical dystonic-dyskinetic syndromes. 3. Methylphenidate 0.5 mg/kg caused increased arousal, but reduced oral dyskinesia, while apomorphine 0.25 mg/kg slightly increased arousal and induced/aggravated oral dyskinesia. 4. Remoxipride 2 and 4 mg/kg and haloperidol 0.005 and 0.01 mg/kg equally antagonized the methylphenidate- and apomorphine-induced arousal, but not oral dyskinesia. 5. Marked sedation was seen when apomorphine was given together with either D2 receptor antagonists. 6. It is concluded that remoxipride and haloperidol have a similar qualitative effect in motor behavior in Cebus monkeys, but the quantitative difference between the dystonia-inducing dose levels of the two drugs compared with the antipsychotic dose levels (estimated from clinical studies) suggests that remoxipride may cause relatively few extrapyramidal side-effects in human.
Gerlach
J
J
Dept. of Psychiatry, Veterans Administration Medical Center, Portland, Oregon.
Casey
D E
DE
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001143:Arousal; D001549:Benzamides / Q000494:pharmacology*; D002428:Cebus; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000503:physiopathology; D010302:Parkinson Disease, Secondary / Q000503:physiopathology; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D017330:Remoxipride
D014150:Antipsychotic Agents; D001549:Benzamides; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D017330:Remoxipride; D006220:Haloperidol