PHARMACOLOGY 



ciplinc of the medical sciences, very nearly ceased to exist, a situation 

 which might not have been long delayed had it not been for the 

 chemotherapeutic advances oi the l&st decade. These, although 

 initiated largely by workers in cognate fields, gave pharmacology a 

 cogent reason for being, and placed renewed emphasis on the fact that 

 the "site" of drug action is not composed of static morphological units. 

 Rather is it to be found in the interrelated chains of chemical reactions 

 which constitute the dynamic equilibrium of the cell. 



That the emphasis on the study of the action of drugs has been 

 placed primarily on the responses of organs and tissues, rather than on 

 those of cells, is well exemplified by the investigations of an important 

 pharmacological agent, viz., digitalis. The cardioactive glycosides of 

 the digitalis and related plants have long been known to affect bene- 

 ficially the function of the decompensated failing heart, an effect now 

 related largely to an increased contractility of the cardiac muscular 

 tissue (5). Yet, few studies have so far been made of the influence of 

 such drugs on the metabolic reactions supplying the energy required 

 for this function of myocardial cells. The validity of such an approach 

 can be examined by investigating the efTect of such drugs on various 

 metabolic reactions and isolated enzyme systems in cardiac and in 

 other forms of muscle. 



The evidence available today, although in some cases circum- 

 stantial, strongly suggests the possibility that the action of many drugs 

 and poisons is mediated through a direct or indirect effect on enzyme 

 systems. This is not a new hypothesis. Myrback (23) made a 

 similar suggestion in 1926, and Clark (6) has reviewed the literature 

 of the subject up to 1937. Consideration of various classes of drugs 

 indicates that in only a few cases is it definitely unlikely that enzyme 

 systems participate in the primary action of drugs or poisons, for 

 instance, saline cathartics and diuretics, adsorbents, neutralizers of 

 alkali or of acid, and hemolytic compounds such as the saponins. It ' ' 

 is equally true that there are only a few cases in which the action of 

 drugs or poisons has been proved beyond question to involve enzyme 

 systems primarily. 



Of perhaps greatest importance, from the standpoint of un- 

 questionable enzymic participation in drug action, is physostigmine 

 (eserine), a potent drug and poison which was shown by Loewi and 

 Navratil (17) in 1926 to inhibit choline esterase specifically. Under 



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