ON THE CHEMOTHERAPY OF NEUROSYPHILIS AND TRYPANOSOMIASIS

We have discussed the relation of chemical constitution of a series of twelve drugs to their activity in neurosyphilis and trypanosomiasis, with special reference, however, to tryparsamide. It is necessary to distinguish clearly between the therapeutic action of tryparsamide in neurosyphilis and its action in trypanosomiasis. In regard to its action in trypanosomiasis, we have come to the following conclusions: (a) that the action of tryparsamide cannot be attributed to any inherent chemical potentiality of the CONH₂ group; (b) that the function of the terminal NH₂ group is to rob the COOH group of its salt-forming power; (c) that an essential element in tryparsamide is the presence of the methylene group in the side-chain attached to the amino nitrogen. In compounds of this type a carbonyl group attached to the amino nitrogen does not increase the therapeutic activity of the parent amino compound.

In support of these propositions, we have shown that phenyloxy-ethylamino-p-arsonic acid is as powerful a trypanocidal agent as tryparsamide. The comparison was made with five different trypanosomal infections in the rat and rabbit, and in the early and late stages of the disease.

In regard to the therapeutic activity of tryparsamide in neurosyphilis, no other drug has been found which produces such striking beneficial results in paresis. Moreover, the therapeutic effect of tryparsamide in paresis can not be explained on the basis of superior penetrating powers of tryparsamide but must be due to certain unknown physical or chemical properties of the drug.

We have discussed the modus operandi of tryparsamide in paresis in regard to clinical and serological improvement.

We have been unable to find any type of laboratory experimentation from which prediction can be made regarding the therapeutic power of such a drug as tryparsamide in neurosyphilis. Animal experimentation in this field shows whether clinical studies are justifiable and the type of pathological reaction the drug may produce in toxic dosage. Clinical investigation alone can indicate its value in neurosyphilis.