The behavioral pharmacology of butaclamol hydrochloride (AY-23,028), a new potent neuroleptic drug.
Butaclamol hydrochloride (AY-23,028) is a member of a new chemical class for which antipsychotic activity in humans has recently been demonstrated. The compound antagonized amphetamine-induced stereotyped behavior in rats, amphetamine toxicity in aggregated mice and apomorphine-induced emesis in dogs. It depressed both discriminated avoidance and continuous lever-pressing behavior in rats and inhibited ambulation and rearing in the open field. At higher doses, AY-23,028 induced catalepsy. Adrenergic blocking activity, measured by the antagonism of epinephrine-induced mortality, was weak. These pharmacological actions are characteristic of neuroleptic drugs. In the dose range where the aforementioned effects were observed AY-23,028 did not antagonize either the tetrabenazine-induced ptosis or the tremorine syndrome and did not cause either hypothermia or ataxia. The potency and onset of action of AY-23,028 were comparable to those of fluphenazine but AY-23,028 was of longer duration. The results are discussed in relation to current concepts of neuroleptic mechanisms.
D000661:Amphetamine / Q000633:toxicity; D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D002746:Chlorpromazine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000633:toxicity; D005476:Fluphenazine / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D014149:Tranquilizing Agents / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy
D003986:Dibenzocycloheptenes; D011807:Quinolizines; D014149:Tranquilizing Agents; D000661:Amphetamine; D001058:Apomorphine; D005476:Fluphenazine; D003913:Dextroamphetamine; D002746:Chlorpromazine; D004837:Epinephrine