ON THE SPIROCHETICIDAL ACTION OF THE ARSPHENAMINES ON SPIROCHETA PALLIDA IN VITRO

¹ From the Syphilis Division of the Department of Medicine, Johns Hopkins Medical School, Baltimore, and the United States Public Health Service, Washington

Arsphenamine, neoarsphenamine, silver arsphenamine and "arsenoxide" (m-amino-p-hydroxyphenylarsenoxide) have been found to immobilize S. pallida in emulsions of rabbit chancres in vitro, and to render them non-infectious for rabbits. Under the experimental conditions here used, these arsenicals are therefore probably spirocheticidal.

The rate at which the immobilization proceeds and the minimal effective concentrations of arsenical depend on numerous variables, some of which are discussed in the text. Thus, activity increases with increasing temperature, and is markedly inhibited by the addition of tissue or tissue derivatives, perhaps because these combine with the arsenical. Inhibition by serum is relatively slight. The action is not demonstrably affected by the anaerobiasis attained in the Brown anaerobe jar.

Under appropriate experimental conditions, arsphenamine, silver arsphenamine, and neoarsphenamine have a definite spirocheticidal effect in vitro within eight hours in as high as a 1:250,000 dilution; and "arsenoxide" is antispirochetal in dilutions of at least one million. It is of interest that these concentrations are of the same order of magnitude as those attained in vivo after the therapeutic administration of these drugs. The extent to which oxidation products of the arsphenamines are responsible for the in vitro effects here described is clearly of primary importance, and is now being studied.