Symposium HYDRAZINE DERIVATIVES OF ISONICOTINIC ACID

The discovery of streptomycin has shown the way by which therapeutic activity against the causative agent of tuberculosis can be found and evaluated in the laboratory prior to its administration in patients. A great number of substances synthesized by the chemist in his laboratory or isolated from natural sources have been found to exert activity against the bacillus of tuberculosis. Many of these show this effect only in the test tube and prove without effectiveness if studied in experimental animals infected with tuberculosis. The new antituberculous agent, isonicotinic acid hydrazide (rimifon®), is a rather simple synthetic compound which was found to be superior to known antituberculous drugs during early stages of the laboratory investigation. Rimifon® possesses not only a remarkably high growth inhibiting effect against the tubercle bacillus in the test tube but also unusual features if studied in infected animals. Most of the fundamental work which has been confirmed in laboratories all over the world was done in mice which were infected with high and fatal doses of human tubercle bacilli. In this infection rimifon® showed 4 characteristic properties which had not been observed with any of the known drugs: (1) the drug protected heavily infected mice after administration of very small doses, (2) the drug successfully prevented the multiplication of the tubercle bacilli in the infected tissues of the animal and therefore (3) produced a lasting protection after discontinuance of therapy, and (4) if given therapeutically in animals in which the disease had already produced its characteristic lesions the drug tended to stop further development of the disease and to prepare the ground for the final cure. In sharp contrast to the broad spectrum antibiotics acting on a multitude of pathogenic bacteria and even viruses, rimifon® is a specific drug in the strict sense of Ehrlich9s concept of chemotherapy in that it exerts its activity only against the group of mycobacteria of which the most important representatives are the tubercle bacillus and bacillus of Hansen9s disease (bacillus leprae).