Printed in U.S.A. NITROPRUSSIDE PRODUCES CYANIDE POISONING

SMrni, ROGER P. AND HARRIET KRUSZYNA Nitroprusside produces cyanide poison-ing via a reaction with hemoglobin. J. Pharmaco!. Exp. Ther. 191: 557-563, 1974. The classical cyanide antagonists, nitrite and thiosulfate, protect laboratory rodents against death by sodium nitroprusside, Na,Fe(CN),,NO. On a molar basis, sodium nitroprusside is at least 4 times more acutely toxic than sodium cyanide to mice. Lethal blood levels of cyanide are found in mice at death after nitroprusside. Cyanide can be released from nitroprusside when the latter is incubated with a variety of biological materials. This reaction is nonenzymatic and apparently involves free sulfhydryl groups. The most active biological preparation tested was blood. The red cells were far more active than plasma, and mouse and rat erythrocytes were more active than human red cells. Hemolysis resulted in even greater activity and abolished the species differences. In solution nitroprusside reacts with oxy- or deoxyhemoglobin to generate cyanmethemo-globin. Such a direct conversion of hemoglobin to cyanmethemoglobin by reaction with a single molecular species has not previously been described. In the presence of dithionite