Effects of some dibenzo-azepines on suppressed and nonsuppressed behavior of squirrel monkeys.
Six dibenzo-azepine derivatives were compared for their effects on suppressed and nonsuppressed behavior of squirrel monkeys. Monkeys responded by pressing a lever under a two-component fixed-ratio schedule of food presentation in which responding in one component was suppressed by response-produced electric shock. Intermediate doses (0.3-1.0 mg/kg IM) of selected unsubstituted and 8-chlorine-substituted dibenzo-azepines (perlapine, 106-094, and clozapine) increased responding that was suppressed by electric shock, whereas selected 2-chlorine-substituted dibenzo-azepines (loxapine, clothiapine, and 105-056) did not consistently increase suppressed responding at any dose (0.001-0.1 mg/kg IM). All six dibenzo-azepines decreased nonsuppressed responding in a dose-related manner, with the 2-chlorine-substituted derivatives being 16-50 times more potent than their unsubstituted or 8-chlorine-substituted congeners. These structure-activity relationships indicate that the effects of the dibenzo-azepines on both suppressed and nonsuppressed behavior differ qualitatively depending on the location of the chlorine substituent.
Spealman
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D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003024:Clozapine / Q000031:analogs & derivatives / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000494:pharmacology; D007266:Inhibition, Psychological; D008152:Loxapine / Q000494:pharmacology; D008297:Male; D012453:Saimiri; D013329:Structure-Activity Relationship
D003984:Dibenzazepines; D003987:Dibenzothiazepines; C045393:11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine; C045392:2-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine; C003910:perlapine; D003024:Clozapine; D008152:Loxapine