Behavioural Changes in Primates and Diazepam Metabolism

Abstract1. Changes in ‘aggression’ and ‘activity’ observed in cynomolgus primates (Macaca fascicularis) following administration of a single 2·5 mg/kg oral dose of diazepam have been related to blood levels and tissue distribution of the parent compound and its major metabolites.2. Distribution of 14C after a single oral dose of [2-14C]diazepam shows rapid absorption, 75% of the dose being absorbed by 2 h at which time highest blood concn. are observed. With the exception of muscle and carcass, tissue-to-blood ratios exceed 1·0 throughout 24 h. High 14C content in excreta between 2 and 12 h after dosing suggests hepatic recycling and/or tissue storage.3. Analyses of blood, brain and muscle from 0·25 to 24 h after dosing show the presence of diazepam and its major metabolites as early as 0·25 h after dosing, the N-desmethyl derivative predominating throughout the 24 h period. The concn. of diazepam in all three tissues falls relatively faster than its metabolites.4. Max. reduction in ‘aggression’ (79%) and...