Comparison of the effects of azathioprine and its novel non-mercaptopurine analog on antibody response in rabbits.

Azathioprine (AZA) was originally developed as a pro-drug of the cytotoxic agent 6-mercaptopurine (6-MP). It was assumed that the methylnitroimidazole (MNI) group attached to 6-MP served only as thiol protecting moiety and was pharmacologically inactive. However, in this study we confirm that the novel compound, 3-[(1-methyl-4-nitro-1H-imidazol-5-yl)thio]-4-methyl-1,2,4-triazole (MNITMT) lacking the 6-MP moiety and retaining the MNI group is a better immunosuppressive agent than AZA. Thus, administration of MNITMT (2 mg/kg/day) to rabbits for two weeks caused a statistically significant and consistent inhibition of the antibody response. The onset of immunosuppression was on day 14. However, administration of AZA (2 mg/kg/day) to rabbits for two weeks inhibited the antibody response significantly on day 60 post-treatment. The solvent used to dissolve the above-mentioned drugs had no effect on the antibody response. Neither AZA nor MNITMT had any effect on the blood picture of the treated rabbits indicating no bone marrow toxicity.