On the Lasting Protective Effect of Hydrazine Derivatives of Isonicotinic Acid in the Experimental Tuberculosis Infection of Mice

¹ Chemotherapy Laboratories, Hoffmann-La Roche Inc., Nutley, N. J.

1) A group of experiments is presented in which mice infected with M. tuberculosis H37Rv by the intravenous or intranasal route received treatment with different anti-tubercular agents for a 21 day period. The success or failure of this treatment was evaluated after an additional 21 day period without any drug administration.

2) Under these experimental conditions, known anti-tubercular agents such as streptomycin, para-aminosalicylic acid, tibione, nicotinaldehyde thiosemicarbazone and isonicotinaldehyde thiosemicarbazone given in doses high enough to protect the mice for the duration of treatment did not prevent an extensive lung involvement after the discontinuance of therapy.

3) Two new anti-tubercular compounds, namely, isonicotinic acid hydrazide, Rimifon, and its isopropyl derivative, Marsilid, on the other hand, prevented in comparatively low dosage ranges the development of the tuberculous lesions in the lungs of a substantial number of the animals observed for the extended period of time. In addition, a marked influence on the mortality rate was observed in case of the intravenous infection.

4) The indications are, therefore, that the results obtained with Rimifon and Marsilid are due to a direct effect on the viability of the causative organisms. However, no claim can be made at the present time that a permanent sterilization of the infected host has been achieved.