Behavioral studies on the enantiomers of butaclamol demonstrating absolute optical specificity for neuroleptic activity.
Butaclamol is a member of a new chemical class for which antipsychotic activity in humans has been demonstrated. Butaclamol, a racemate, has been resolved into its optical isomers and a separation of activities was found to occur between the (+) and (-) enantiomers. The present experiments show that at doses ranging from 0.1 to 0.3 mg/kg the (+) enantiomer abolished amphetamine-induced (a) stereotyped behavior and (b) rotational behavior in rats with unilateral lesions in the substantia nigra. It also inhibited the lever-pressing response in the continuous (Sidman) avoidance procedure, blocked discriminated avoidance behavior, and decreased ambulation and rearing in the open field. In contrast, the (-) enantiomer was devoid of behavioral activity at 100-500 times larger doses. At considerably higher doses (+)-butaclamol antagonized epinephrine-induced mortality. Again, the (-)-butaclamol was devoid of this activity as well. The significance of absolute optical specifity manifested by a neuroleptic drug is discussed in the light of dopaminergic and adrenergic mechanisms.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D003913:Dextroamphetamine / Q000494:pharmacology; D004347:Drug Interactions; D004837:Epinephrine / Q000633:toxicity; D006801:Humans; D007536:Isomerism; D008297:Male; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000502:physiology; D014149:Tranquilizing Agents
D014150:Antipsychotic Agents; D014149:Tranquilizing Agents; D003913:Dextroamphetamine; D004837:Epinephrine