Mat 21, 1920] 



SCIENCE 



499 



stitutionally as emotional as the " coqueros." 

 Wevertlieless sufficient nervous stimulation is 

 derived to render cocaine a dangerous habit- 

 forming' drug. 



After the manner of chemists with a new 

 product, Wohler tasted cocaine and noted (to 

 translate literally), that "it is bitter and 

 exerts upon the tongue nerves a characteristic 

 effect in that the point touched becomes tem- 

 porarily numb, almost without sensation." 

 Twenty-four years elapsed before the signifi- 

 cance of this finding was fully appreciated; 

 Koller, a Viennese oculist, in 1884 intro- 

 ducing it as a practical local anesthetic for 

 the eye. In the meantime, however, Parisian 

 workers had noted anesthesia of the tongue 

 when the leaves were chewed with alkali (De- 

 Marie, 1862); and Moreno y Maiz (1868), 

 had suggested the employment of the drug as 

 a local anesthetic. A number of fundamental 

 pharmacological facts about cocaine were 

 demonstrated by Von Anrep^ (1880). 



From the eye clinic the use of the drug 

 spread to laryngology find rhinology and later 

 to general surgery. As it is typical of a large 

 class of local anesthetics its action may now 

 be somewhat more fully detailed. 



Cocaine is classed as a " general protoplasm 

 poison," since relatively small amounts exhibit 

 the power to interrupt or suppress the life 

 process both of lower and higher organisms. 

 In mammals it attacks nerve tissue in par- 

 ticular and there are acute and chronic types 

 of brain poisoning, the latter, of course, being 

 illustrated in the widespread abuse of the 

 drug. Acute poisoning (motor excitement 

 and high temperature followed by convulsions) 

 has been noted in all attempts at anesthetiza- 

 tion of animals by intravenous injection or 

 other means of introducing the drug into the 

 general circulation. The local or peripheral 

 action can not be obtained by such methods. 



The portions of the nervous system upon 

 which the action is useful are the nerve 

 trunks and their sensory endings, and as may 

 be judged from the above, one problem of the 

 surgeon is to keep the substance limited as far 



4 Von Anrep, B., P finger's Archiv. der Physiol- 

 ogie, 1880, 21, 3S. 



as possible to these regions. On the nerve 

 trunks it has a selective action in blocking 

 afferent or sensory impulses much more 

 readily than efferent or motor impulses, both 

 of which are carried by the same bundle of 

 nerve fibrils. Its selective action is further 

 illustrated by the abolition, upon application 

 to the nerve ends, of pain and touch sensa- 

 tions, while the perception of heat and cold 

 remains iminterrupted. Again, on the tongue, 

 in addition to touch and pain, the perception 

 of " bitter " taste is completely eliminated, yet 

 those sensations which we describe as " sweet " 

 and " acid " taste are still dimly perceived, 

 while the presence of salt may still be appre- 

 ciated as well as ever. 



That cocaine is not an ideal local anesthetic 

 can be readily appreciated. Aside from its 

 disadvantages as a habit-forming drug and 

 the possibility of the development of toxic 

 symptoms if unskillfvdly employed, there are 

 minor objections which include the possibility 

 of injury to the tissues or interferences with 

 natural processes of repair if given in too 

 concentrated a solution and the fact that 

 solutions if sterilized by boiling undergo some 

 decomposition. 



Since these facts began to receive attention 

 the production and testing of synthetic sub- 

 stitutes for cocaine has been a nearly con- 

 tinuous performance. As the structural 

 formula of the alkaloid shows, it is the methyl 

 ester of benzoyl ecgoniu : 



CHr 



-CH 



I 



-CHj 



CHr 



N(CH)3 CH-O-CO-CsHs 

 I I 

 CH CH • CO ■ OCH3 



Its decomposition products are methyl alco- 

 hol, benzoic acid and the tropine-like base 

 ecgonine. Investigations by Filehne, Paul 

 Ehrlich, and others, were undertaken to deter- 

 mine in which of these chemical groups or in 

 what combination of radicals the anesthetic 

 virtues resided. The benzoic acid radical was 

 soon indicated as being of importance; for 

 example, neither ecgonin nor methyl ecgonin 

 were fomid at all like cocaine in their action. 

 On the other hand the isomer of cocaine in 

 which the methyl and benzoyl radicals were 



