ANTAGONISM OF THE LETHAL EFFECTS OF CYANIDE BY A SYNTHETIC WATER-SOLUBLE COBALT(III) PORPHYRIN COMPOUND

Efficacy of hydroxocobalamin (vitamin B-12) as a cyanide antidote is l imited by its high molecular weight(1355 g/mol) and by the competitive binding of the cobalamin dimethylbenzimidazole. The present study des cribes experiments with a lower molecular weight cobalt porphyrin that has a high affinity for cyanide, Co(III)-5,10,15,20-tetrakis(4-sulfon atophenyl) porphyrin (CoTPPS), which was prepared by the method of Her rmann et al. (1978). CoTPPS was synthesized and its efficacy as an ant idote to the lethal effects of cyanide either alone or in various comb inations with NaNO2 and/or Na2S2O3 was determined. The LD50 value for CoTPPS was found to be 334 mg/kg. These studies were conducted using t he CoTPPS LDO1, 200 mg/kg. The cyanide antagonists NaNO2 (0.1 g/kg, sc ), Na2S2O3 (1.0 g/kg, ip), and CoTPPS (0.2 g/kg, ip) were administered at 45, 15, and 10 min respectively prior to graded doses of KCN (sc). The LD50 values for KCN in male Swiss-Webster mice were calculated by probit analysis at the 95% confidence level and the various treatment s were compared by potency ratios. These results indicated that the ad ministration of CoTPPS alone protects against the lethal effects of cy anide. Moreover, CoTPPS adds to the protection provided by Na2S2O3 and /or NaNO2. Efficacy of this antidote is probably related to the bindin g equilibrium between CoTPPS and cyanide. (C) 1994 Society of Toxicolo gy.