title: Neuroleptic properties of cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide (YM-09151-2) with selective antidopaminergic activity.
abstract: A new benzamide, cis-N-(1-benzyl-2-methylpyrrolidin - 3 - yl) - 5 - chloro - 2 - methoxy - 4 - methylaminobenzamide (YM-09151-2) exhibited more potent and longer-lasting inhibitory effects on apomorphine-induced behaviours (stereotyped behaviour, emesis and hypothermia), and methamphetamine-induced stereotyped behaviour, conditioned avoidance response and open field behaviour, conditioned avoidance response and open field behaviour than either structurally similar benzamides (YM-0850 and sulpiride) or classical neuroleptics [chlorpromazine (CPZ) and haloperidol(HPD)]. Such inhibitory effects of YM-09151-2 relative to cataleptogenicity were greater than those of CPz and HPD. In contrast, sulpiride elicited few of the neuroleptic effects described above. YM-09151-2, a potent inhibitor for dopamine-sensitive adenylate cyclase (Ki: 3.0 nM) reduced, in a selective manner, the binding of [3H]dopamine to the dopamine D1 receptor (Ki:4.8 nm) associated with adenylate cyclase rather than to the dopamine D2 receptor (Ki: 0.98 microM) independent of adenylate cyclase. Sulpiride, on the contrary, inhibited only the binding to the dopamine D2 receptor, CPZ and HPD antagonized [3H]dopamine nonselectively at the two distinct dopaminergic receptors. These results suggest that YM-09151-2 is a potent and long-lasting neuroleptic with a highly selective blocking action on the dopamine D1 receptor.
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine; D001549:Benzamides / Q000494:pharmacology*; D002747:Chlorpropamide / Q000494:pharmacology; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D007035:Hypothermia / Q000188:drug therapy; D008297:Male; D008694:Methamphetamine; D051379:Mice; D008813:Mice, Inbred ICR; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D014839:Vomiting / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D001549:Benzamides; D011954:Receptors, Dopamine; D008694:Methamphetamine; C022913:YM-08050; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine; C030265:nemonapride; D002747:Chlorpropamide