Activity of the chloro- and triazolo-benzodiazepines: Behavioural studies in the monkey ( Macaca mulatta)

Abstract

The effects of 1,4-benzodiazepines with various heterocyclic ring structures (triazolo, triazino and imidazo), and of 1,4-benzodiazepines with chlorine substitution in the phenyl ring (4'-chlorodiazepam, 2'-chlorodiazepam and 2'-chloronordiazepam) were studied on spatial-delayed alternation and delayed matching-to-sample tasks in the monkey. Within the dose range 0.25–0.75 mg kg −1, the triazolo compounds had marked activity, decreasing the number of correct responses and increasing total response time. The triazino was less potent and the imidazo compounds were the least likely to disrupt performance. Smaller doses (0.005, 0.01 and 0.05 mg kg −1) of triazolam did not impair performance on the tasks, and larger doses of imidazo (1.0, 3.0 and 7.5 mg kg −1) were without effect on delayed alternation. Within the dose range 1.0–10.0 mg kg −1, 4'-chlorodiazepam was without effect and only the largest dose of diazepam and 2'-chlorodiazepam impaired performance. 2'-chloronordiazepam decreased the number of correct responses at all doses (1.0, 3.0 and 10.0 mg kg −1) and with the largest dose, the total response time was increased. The studies suggest that the effects of a drug on higher nervous function in the monkey cannot easily be predicted from standard pharmacological tests in other animals or other species of monkey.