Effects of some dibenzo-azepines on suppressed and nonsuppressed behavior of squirrel monkeys

Psychopharmacology (Berl). 1985;85(2):129-32. doi: 10.1007/BF00428400.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects*
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology
  • Dibenzazepines / pharmacology*
  • Dibenzothiazepines / pharmacology
  • Inhibition, Psychological
  • Loxapine / pharmacology
  • Male
  • Saimiri
  • Structure-Activity Relationship

Substances

  • Dibenzazepines
  • Dibenzothiazepines
  • 11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine
  • 2-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo(b,e)(1,4)diazepine
  • perlapine
  • Clozapine
  • Loxapine