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.
Al-Safi
Saafan
S
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science & Technology, P.O. Box 3030, Irbid 22110, Jordan. alsafi52@yahoo.com
Tashtoush
Bassam
B
Hassan
Mohamad
M
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001379:Azathioprine / Q000009:adverse effects / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D006454:Hemoglobins / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects; D011817:Rabbits; D014230:Triazoles / Q000009:adverse effects / Q000494:pharmacology*
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D014230:Triazoles; C048848:JJC 323; D001379:Azathioprine