Effects of picrotoxin, naloxone, and vagotomy on chlordiazepoxide-induced respiratory depression.

Intravenous administration of chlordiazepoxide (CDP) caused respiratory depression in both rats and cats. The maximally tolerated dose of CDP was found to be 165 +/- 15 mg/kg, i.v., in rats. Pretreatment with picrotoxin (1.5 mg/kg) or naloxone (20 mg/kg, i.v.) significantly increased the maximally tolerated dose of CDP to 330 +/- 40 mg/kg, i.v., and 270 +/- 35 mg/kg, i.v., respectively. The protective effects of both naloxone and picrotoxin were absent in bilaterally vagotomized rats. Naloxone pretreatment (25 mg/kg, i.v.) was also found to block the respiratory depressant effects of CDP in anesthetized cats, but had no effect on the cardiovascular actions of CDP. It is possible that the respiratory effects of CDP are due to its actions on GABA receptors, and that peripheral GABA receptors may mediate the protective actions of picrotoxin and naloxone.