Chemical Structure of the Opium Alkaloids. 65 



lowering action resides in the benzyl part of the papaverin mole- 

 cule. 



These observations and conclusions logically led the author to 

 surmise that possibly the inhibitory and tonus-lowering effect of 

 papaverin might be produced by the exhibition of a benzyl group- 

 ing in a simpler form. Accordingly a search was made for simple 

 non-alkaloidal and non-narcotic compounds containing the benzyl 

 radical which could be administered to animals without toxic 

 results. Two such bodies were discovered. They were the well- 

 known esters, benzyl-benzoate and benzyl-acetate. Inasmuch as 

 these esters are practically insoluble in water, their pharmaco- 

 logical action could not be studied on excised tissues, but experi- 

 ments on intact animals revealed the fact that both of these esters 

 actually produced the same pharmacological effects as those given 

 by the opium alkaloid papaverin, on the one hand, and that these 

 esters were much less toxic than papaverin, on the other. Meta- 

 bolic studies in connection with these experiments showed that 

 the benzyl group of benzyl-benzoate and benzyl-acetate is in a 

 large measure converted into hippuric acid in the body and is 

 excreted as such in the urine. The comparatively very low 

 toxicity of benzyl-benzoate and benzyl-acetate for animals and 

 their striking papaverin-like effects on various viscera led the 

 author to try their action upon himself and as no untoward or even 

 disagreeable symptoms followed the ingestion of these drugs by 

 mouth, it was deemed justifiable to administer these agents to 

 suitable patients with their consent. 



The conditions in which the benzyl effect was anticipated to 

 produce pharmacological result, were those exhibiting either 

 excessive peristalsis or excessive spasm of smooth muscle. It 

 would take too much space in this preliminary communication to 

 describe in detail all the cases in which benzyl-benzoate for the 

 most part and benzyl-acetate to a lesser extent, were tried. The 

 author need only state in this place that the oral administration 

 of these esters was followed by remarkable pharmacological and 

 therapeutic results of a beneficial character in the following con- 

 ditions: (1) Excessive peristalsis and colic of the intestines, 

 namely, in cases of diarrhea and dysentery. (2) Spasm and colic 

 of the ureteral smooth muscle, that is, "renal colic." (3) In 



