PHARMACOLOGY 



participate in the inactivation of epinephrine and the closely related 

 or probably identical neurohormone, sympathin, responsible for the 

 chemical transmission of adrenergic impulses. Inhibition of the 

 enzyme leads to the accumulation of epinephrine in much the same 

 way that physostigmine protects acetylcholine from destruction. The 

 stimulant action of amphetamine (benzedrine) on certain functions 

 of the central nervous system was related by Mann and Quastel (20), ' i 

 in a rather complicated theory, to inhibition of the oxidative deami- 

 nation of compounds such as tyramine, which is deri\ ed from tyrosine. 

 It was suggested that the type of mental fatigue relieved by amphet- 

 amine is due to the formation, by amine oxidase, of toxic aldehydes 

 from compounds such as tyramine. Central excitation is thus con- 

 sidered to be secondary to an inhibition of amine oxidase. Needless 

 to say, the acceptance of such an hypothesis requires a great deal more 

 evidence than that so far made available. 



Amine oxidase is undoubtedly responsible for the oxidative 

 deamination which many of the sympathomimetic amines undergo in 

 the body (2) and is thus responsible, in part at least, for their inactiva- 

 tion. Derivatives of phenethylamine which possess an alkyl group 

 alpha to the nitrogen, such as amphetamine and ephedrine, are not 

 only refractory to the action of amine oxidase, but are capable of 

 inhibiting markedly the action of the enzyme. 



The enzymic approach to the study of the mode of action of 

 drugs is by no means limited to those compounds which aflfect mam- 

 malian tissues. The chemotherapy of infectious and parasitic diseases 

 is based on the use of compounds which in suitable dosage have less 

 efTect on chemical reactions essential to the well-being of the host , 

 than on those reactions requisite to the life or reproduction of invasive 

 organisms. Thus, chemotherapeutic agents vary in their margins 

 of safety from those that are of the same order of toxicity for both host 

 and parasite to those that are essentially devoid of deleterious eflfects 

 on any mammalian host. Examples of such extremes are actually to 

 be found among drugs which may be used in the treatment of a single ; | 

 disease, like syphilis. Thus, metallic mercury, when used by inunction, / 

 is of such toxicity that it is possible only to arrest the progress of the \ 

 infection, while with highly purified penicillin not only may apparent ( 

 cures be produced but man appears to be essentially uninjured by any J 

 dose so far administered. 



