44 



Scientific Proceedings (102). 



24 (1484) 



Concerning the toxicity of acetanilid and bicarbonate combina- 

 tions for muscle-nerve preparations. 



By David I. Macht. 



Pharmological Laboratory, Johns Hopkins University.] 



It is well known, through the work of Worth Hale, 1 that ace- 

 tanilid when given in combination with small doses of sodium 

 bicarbonate, is less toxic than when administered in the same 

 doses alone. The studies of Macht, Greenberg and Isaacs on the 

 influence of antipyretics on the acuity of hearing 2 have also 

 shown an interesting difference between the effects of acetanilid 

 when given alone and acetanilid when combined with sodium 

 bicarbonate. The explanations given for the above peculiar 

 synergism are most unsatisfactory- . In connection with a pharm- 

 acological study of various antipyretics, the author investigated 

 the effect of acetanilid solutions on muscle-nerve preparations 

 which may throw some light upon the above-mentioned 

 phenomena. 



Two gastrocnemius muscle-nerve preparations of a frog are 

 immersed simultaneously in physiological sodium chloride solution 

 and the limits of both the muscle and nerve excitability to the 

 electric shocks of an induction coil are determined. One of the 

 preparations is then immersed in a solution of acetanilid in the 

 same saline solution, and the other preparation is immersed in a 

 solution of acetanilid of exactly the same strength but containing 

 some sodium bicarbonate (1-1000 or even weaker). On testing 

 the excitability of the muscles and nerves at regular intervals after 

 treatment with the drugs, it was found that the plain acetanilid 

 solution tends to paralyze and finally kill the sciatic nerve more 

 quickly than the solution of acetanilid plus bicarbonate. The 

 following protocol of an experiment thus performed will serve as an 

 illustration. The slower toxic action of the acetanilid and bicar- 

 bonate combination, all other factors being equal would, it is fair 

 to assume, render the drug less poisonous when injected into an 



1 U. S. Hygienic Lab. Bulletin No. 53 (1909). 



1 Proc. Soc. for Exper. Biol, and Med.. 1919. xvii, 22. 23. 



