Chloral hydrate and meperidine: Response and metabolism in squirrel and rhesus monkeys

Abstract

Using eyelid ptosis and hypothermia as criteria, the pharmacological response of male rhesus and squirrel monkeys to chloral hydrate (CH) and meperidine (MP) was determined. Squirrel monkeys were found to be approximately three times more sensitive to CH than were rhesus monkeys. Studies on the metabolic disposition of pharmacologically effective doses of CH in the two species (150 and 500 mg/kg for squirrel and rhesus monkeys, respectively) indicated that squirrel monkeys were more sensitive to CH because of a greater capacity to form the active metabolite, trichloroethanol. Comparison of effective doses in these monkeys with those for man indicates that squirrel monkeys and man were about equally sensitive to CH, but that rhesus monkeys were relatively insensitive. Similar studies using MP showed that rhesus monkeys were about twice as sensitive to this drug than were squirrel monkeys. Studies on the metabolic disposition of pharmacologically effective doses of MP in the two species (3.5 and 8.0 mg/kg for rhesus and squirrel monkeys, respectively) indicate that squirrel monkeys were inherently less sensitive to MP and were more capable of forming the nondepressant metabolite, normeperidine, than were rhesus monkeys. Comparison of effective doses in these monkeys with those for man indicated that rhesus monkeys and man were about equally sensitive to MP, but that squirrel monkeys were less sensitive.