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[N. S. Vol. LI. No. 1325 



made to exchange places, exhibited no local 

 anesthetic properties; when,' however, the ben- 

 zoic acid radical was replaced in the cocaine 

 structure by other homologous acids, sub- 

 stances with cocaine-like action were evolved. 

 Einhom, who had earlier been associated 

 with Ehrlich's work, introduced as a local 

 anesthetic orthofoi-m. This is the methyl 

 ester of an oxy-benzoic acid modified by the 

 introduction of an amino group to replace 

 the very complicated base ecgonine. This 

 substance, while poorly soluble, has found a 

 place in surgery as an anesthetic dusting 

 powder. Einhorn' next modified the ortho- 

 form grouping in such a way as to produce 

 more soluble compounds, but achieved his 

 greatest success by the introduction of the 

 " alkamine " esters of benzoic acid, notably 

 procaine (known also by the trade name of 

 novocaine) : 



—CO— O— CH2— CHsNCCsHs)., HCl 



N / 



In other synthetic compounds (stovain, 

 alypin, and B-eucaine), no amino group ap- 

 pears on the benzene nucleus. In still an- 

 other series of compounds, the benzoyl group 

 has by an intervening side-chain been at- 

 tached to the nitrogen of the ecgonine mole- 

 cule. This work was reported recently by 

 Wichura' (1918) and one of the compounds, 

 apparently giving promise, is known as eccain. 



Another natural alkaloid has been obtained 

 from the small coca leaves of Java. This 

 substance, tropacocaine, was found by Dr. 

 Arthur P. Chadbourne' (1892), of Boston, to 

 possess valuable anesthetic properties. Simi- 

 lar in structure to cocaine (of which it is in 

 many ways the equal) it contains pseudo- 

 tropine in place of the ecgonine radical. 



In the group of antipyretic drugs also are 

 foimd substances of value as local anesthetics, 



6 Einhom, Liehig's Annalen, 1908, 359. 



« Wichura, Wilhelm, Zeits. fiir Exper. Path, and 

 Therapie, Vol. 20, p. 1. 



T Chadbourne, A. P., Brit. Med. Jour., 1892, II., 

 402. 



although these are chemically quite unrelated 

 to cocaine. Among them are holocaine, a 

 phenacetin derivative, and quinine, which is 

 used in combination with urea. In 1913, 

 Morgenroth showed that certain quinoline 

 derivatives have a similar action, including a 

 group of substances which also give promise 

 of a specific value in the treatment of pneu- 

 monia. Antipyrine may be included in this 

 and in the following gi'oup. 



In 1888, Liebreich^ called attention to the 

 fact that a large number of substances are 

 capable of producing " anesthesia dolorosa." 

 This term is applied to the phenomenon of 

 smarting followed by loss of sensation. 

 Among the substances which he enumerated 

 were sodimn bromide, ammonium chloride, 

 lead acetate, ferric chloride, resorcin, and 

 even the glueosides saponin and nap6llin. 

 Carbolic acid affords the most conspicuous ex- 

 ample of this type, its action culminating as 

 is well known in the death of tissue. 



In spite of the untoward effects of carbolic 

 acid, which is an aromatic alcohol, certain 

 closely related aromatic side-chain alcohols 

 are now yielding much promise of practical 

 value. Dr. David I. Macht,^ of Baltimore, 

 the pioneer in this field, a few years ago noted 

 the anesthetic effect of benzyl alcohol upon 

 the tongue, demonstrated its highly innocuous 

 character, and was instrumental in intro- 

 ducing it into surgery. 



In our laboratory three similar side-chain 

 aromatic alcohols have been tested, chiefly by 

 Dr. Axel M. HJort,^" whose work has been 

 aided by the Committee on Scientific Re- 

 search of the American Medical Association. 

 As will be seen from the following summary 

 of Dr. Hjort's findings, two of these, rose oil 

 and benzoyl carbinol, possess a high degree of 

 anesthetic efficiency combined with a low de- 

 gree of toxicity. 



8 Liebreieh, Verhandl. de 7 Kongr. f. tnn. Medi- 

 lin, 1888, S. 245. 



9 Macht, D. I., Jour. Pharm. and Exp. Therap., 

 1918, XI., 263. 



lO-Hjort, A. M., and Kaufmann, C. E., Proo. Sac. 

 Exp. Biol, and Med., January, 1920. 



