Isonicotinylhydrazine (INH)

Isonicotinylhydrazine (INH), is an organic compound that is the first-line medication in prevention and treatment of tuberculosis. Isoniazid is available in tablet, syrup, and injectable forms. It is manufactured from isonicotinic acid, which is produced from 4-methylpyridine. Isoniazid is a prodrug and must be activated by a bacterial catalase-peroxidase enzyme that in M. tuberculosis is called KatG. KatG couples the isonicotinic acyl with NADH to form isonicotinic acyl-NADH complex. This complex binds tightly to the enoyl-acyl carrier protein reductase known as InhA, thereby blocking the natural enoyl-AcpM substrate and the action of fatty acid synthase. This process inhibits the synthesis of mycolic acid, required for the mycobacterial cell wall. A range of radicals are produced by KatG activation of isoniazid, including nitric oxide, which has also been shown to be important in the action of another antimycobacterial prodrug PA-824.