Comparative study on the depressive action of several benzodiazepine minor tranquilizers

Abstract

The potencies of four benzodiazepine minor tranquilizers in depressing respiratory function were investigated in rats and cats anesthetized with pentobarbital. The effect of the drug on respiration was studied in the rat, and the effect on the phrenic nerve activity which reflects the activity of an inspiratory centre was investigated in the cat vagotomized bilaterally at the level of the neck. The change of blood pressure, heart rate and pCO² in expiration were also recorded simultaneously in experiments witn the cat, an infra-red CO₂ gas analyzer (Model LB-1, Beckman) was used to measure the pCO₂. Respiration in the rat was decreased by the oral administration of diazepam 10, 20 mg/kg or chlordiazepoxide 20, 40 mg/kg. Although the pre-administration level of ventilation was not decreased by oxazolam or cloxazolam, both 20, 40 mg/kg, p.o., the level after administration was slightly lower than that after the administration of CMC alone. Diazepam, given intravenously either as a CMC-suspension or as the preparation Cercine®, in the dose of 0.5 mg/kg, suppressed both the number of the burst discharges and the magnitude of the integrated signal of the discharge of the phrenic nerve of the cat. Chlordiazepoxide 1 mg/kg, i.v. also slightly decreased the magnitude of the integrated signal. Oxazolam 1 mg/kg, i.v. had little effect on the phrenic activity. Cloxazolam 1 mg/kg, i.v., on the other hand, tended to increase the magnitude of the integrated signal but only immediately after the administration. It is suggested that the potencies which depress the respiratory function vary for each minor tranquilizer, namely the depressive actions of oxazolam and cloxazolam are weaker than those of diazepam and chlordiazepoxide.