Document Detail

Antagonism of the lethal effects of cyanide by a synthetic water-soluble cobalt(III) porphyrin compound.
MedLine Citation:
PMID:  7958566     Owner:  NLM     Status:  MEDLINE    
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.
W D McGuinn; L Baxter; L Pei; I Petrikovics; E P Cannon; J L Way
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Fundamental and applied toxicology : official journal of the Society of Toxicology     Volume:  23     ISSN:  0272-0590     ISO Abbreviation:  Fundam Appl Toxicol     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-12-01     Completed Date:  1994-12-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8200838     Medline TA:  Fundam Appl Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  76-80     Citation Subset:  IM    
Department of Medical Pharmacology and Toxicology, Texas A&M University, College Station 77843-1114.
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MeSH Terms
Antidotes / pharmacology*
Cyanides / antagonists & inhibitors*,  toxicity
Lethal Dose 50
Metalloporphyrins / chemical synthesis,  pharmacology*
Reg. No./Substance:
0/Antidotes; 0/Cyanides; 0/Metalloporphyrins; 91629-46-8/cobalt(III)-tetrakis(4-sulfonatophenyl)porphyrin

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