BIOCHEMICAL ANTAGONISM 



logical action of benzimidazolc mighl be an expression of its structural 

 relation to adenine. However, since adenine did not reverse the 

 effect of benzimidazolc on animals, more concrete evidence will be 

 necessary before the action of the drug can l)e explained. Eventually, 

 the modus operandi of some drugs may be viewed merely as the result of 

 the production of a deficiency of a structurally related metabolite at 

 the site of action of the drug. * Some drugs now under investigation 

 or in use can be pictured as structural analogues of certain metabolites. 

 Furthermore, the effects produced arc not unlike those which might 

 be expected to result from the removal of the analogous metabolite 

 from the field of metabolic action. Nevertheless, it must be re- 

 membered that these are speculations and that they demand experi- 

 mental proof before they can be accepted. 



Further conjectures along this line may be applied in con- 

 sideration of antagonisms known to exist among various pairs of metab- 

 olites. For example, it has been shown that androgens and estrogens 

 may occur together in both sexes, and that pharmacologically they 

 exhibit certain antagonisms. Perhaps these are the result of the 

 structural relationship between these htjrmones. 



Although we may think that antagonisms between metabolites 

 and their structural analogues pojiped into the world with the advent 

 of the nutritionist and the organic chemist, this is probably not so. 

 For example, Chromobacterium iodinum has been found to produce a 

 pigment which is bacteriostatic and is a structural relative of some 

 naturally occuring anthraquinones, and more remotely of vitamin K. 

 These anthraquinones, as well as vitamin K, reverse the action of 

 the antibiotic pigment. Similarly, 3,3'-methylenebis-[4-hydroxy- 

 coumarin], a structural analogue which elicits some of the signs of 

 vitamin K deficiency, was first discovered in spoiled sweet clover hay. 



At this point it is well to contemplate some hypotheses re- 

 garding the mechanism of action of the sulfonamides in bacteriostasis, 

 and these same hypotheses as they are applied to inhibitory analogues 

 in general. After the discovery of the reversal of sulfonamide bac- 

 teriostasis by /;-aminobenzoic acid, the hypothesis was advanced that 

 the sulfonamides competed with />-aminobenzoic acid for a place on 



* It is, of course, not expected that all types of drug action will find ex- 

 planation in biochemical antagonism. 1 1 is merely suggested that some pharma- 

 cological agenls may owe their biological potency to this phenomenon. 



3^5 



