Antagonism of the lethal effects of cyanide by a synthetic water-soluble cobalt(III) porphyrin compound.
Efficacy of hydroxocobalamin (vitamin B12) as a cyanide antidote is limited by its high molecular weight (1355 g/mol) and by the competitive binding of the cobalamin dimethylbenzimidazole. The present study describes experiments with a lower molecular weight cobalt porphyrin that has a high affinity for cyanide, Co(III)-5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (CoTPPS), which was prepared by the method of Herrmann et al. (1978). CoTPPS was synthesized and its efficacy as an antidote to the lethal effects of cyanide either alone or in various combinations with NaNO2 and/or Na2S2O3 was determined. The LD50 value for CoTPPS was found to be 334 mg/kg. These studies were conducted using the CoTPPS LD01, 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 treatments were compared by potency ratios. These results indicated that the administration of CoTPPS alone protects against the lethal effects of cyanide. Moreover, CoTPPS adds to the protection provided by Na2S2O3 and/or NaNO2. Efficacy of this antidote is probably related to the binding equilibrium between CoTPPS and cyanide.
McGuinn
W D
WD
Department of Medical Pharmacology and Toxicology, Texas A&M University, College Station 77843-1114.
Baxter
L
L
Pei
L
L
Petrikovics
I
I
Cannon
E P
EP
Way
J L
JL
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D003486:Cyanides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice
D000931:Antidotes; D003486:Cyanides; D008665:Metalloporphyrins; C056134:cobalt(III)-tetrakis(4-sulfonatophenyl)porphyrin