Abstract

Parathion, paraoxon, malathion, disulfoton and carbaryl, but not octamethyl pyrophos-phoramide, prolonged hexobarbital sleeping time in the mouse. The increase in sleeping time was apparently not due to an inhibition of cholinesterase or to an altered sensitivity of the brain to the barbiturate. The effect appeared to be more closely related to an impairment of hexobarbital metabolism since only those insecticides which inhibited hexobarbitol oxidation in vitro prolonged sleeping time. Most of the insecticides, except octamethyl pyrophosphoramide, also depressed the microsomal metabolism of aniline and ethylmorphine in the mouse. Paraoxon was unusual in that it enhanced, rather than in hibited, aniline hydroxylase activity in the mouse, rat, rabbit and dog. Malathion and carbaryl inhibited hexobarbital and aniline metabolism in all species examined, whereas octamethyl pyrophosphoramide had relatively little effect on the rates of drug metabolism. The kinetics of the inhibition varied both with the substrate and with the insecticide employed. A potentiation of carbaryl toxicity was demonstrated by pretreatment of mice with either tolbutamide or bishydroxycoumarin.