244 1. lODOACETATE AND lODOACETAMIUE 



general inhibit glycolysis and often give the Lundsgaard effect on skeletal 

 muscle. Peters and Wakelin (1949) were inclined to relate the inhibition to 

 pyruvate oxidase. lodoacetamide is a potent inhibitor of this enzyme 

 (pigo = 4.3) but no data on its vesicant action were available, except that 

 one of the authors produced a large erythematous patch by subdermal 

 injection of 1.5 mg. Flesch and Goldstone (1950) had experimentally shown 

 iodoacetic acid to be a primary irritant, and that 10 min contact is sufficient 

 to cause a painful bullous lesion, followed by superficial epidermal necrosis. 

 Two cases of dermatitis due to iodoacetic acid were reported by IMarcus 

 and Frerichs (1950). A chemist allowed some iodoacetic acid solution to 

 trickle over his hands and immediately washed it off; in 5 hr the fingers 

 burned and a bullous eruption occurred and in 2 days there were large 

 bullae on the palmar surfaces of all fingers, and on palms and wrists. Heal- 

 ing required almost a month. The other case presented similar findings, in- 

 cluding erythema, vesicles, and depigmentation, and also required a long 

 time to heal. Application of 0.3 ml 5-10% solutions of iodoacetic acid to 

 depilated areas of guinea pig skin leads to vesication, erythema, itching, 

 separation of the epidermis from the corium, and eventual healing in several 

 days (Flesch et al., 1952). One may note that despite much talk about the 

 vesicant actions of iodoacetate and its relation to SH reaction, very few 

 experiments have been done. In most cases no controls were run; for exam- 

 ple, it migh tbe interesting to see what 5-10% acetic acid would do to dep- 

 ilated guinea pig skin. And one must always ask whether at least some ol 

 the effects noted are due to a nonspecific acid effect. In connection with the 

 vesicant action of iodoacetate when applied locally, it is interesting that 

 edema produced subcutaneously by injections of formalin or dextran is 

 quite well prevented in rats by injections of iodoacetate (Stenger, 1959). 

 However, subcutaneous injections of iodoacetate cause swelling. 



EFFECTS OBSERVED IN THE WHOLE ANIMAL 



The toxic effects observed on administration of near-lethal doses of bromo- 

 acetate and iodoacetate are mainly referable, during the early stages of 

 poisoning, to the central nervous and cardiovascular systems. The original 

 observations of Steinauer (1874) and Pohl (1888) on the sequence of toxic 

 reactions in frogs and rabbits given bromoacetate have been presented 

 (pages 1-2). 



Distribution in Animals 



The effects upon various tissues in an animal may depend to some extent 

 on the distribution of an inhibitor in the tissues. Thomassen and Leicester 

 (1951 ) studied the distribution of iodoacetate-I^^^ in rats after intraperitoneal 

 injection of a toxic dose in an investigation of the effects of iodoacetate on 



