Stereospecific effect of naloxone hydrochloride on cyanide intoxication

Abstract

Cyanide intoxication in mice can be antagonized by the opiate antagonist, (−)naloxone HCl, alone or in combination with sodium thiosulfate and/or sodium nitrite. Potency ratios, derived from LD50 values, were compared in groups of mice pretreated with sodium nitrite (sc, 100 mg/kg), sodium thiosulfate (ip, 1 g/kg), and (−)naloxone HCl (sc, 10 mg/kg) either alone or in various combinations. These results indicate that naloxone HCl provides a significant protection against the lethal effects of potassium cyanide. The protective effect of sodium thiosulfate, but not sodium nitrite, was enhanced with (−)naloxone HCl. The combined administration of sodium nitrite and sodium thiosulfate was further enhanced with (−)naloxone HCl. This protective effect of naloxone HCl against the lethal effect of cyanide appears to be restricted to the (−) stereoisomer, as the (+) stereoisomer, the inactive opiate antagonist, is also inactive in protecting against the lethal effects of cyanide. The mechanism of antagonism is discussed.