Isoniazid is an antibiotic used for the treatment of tuberculosis, also used for some nontuberculous mycobacterial infections and given orally or by injection. It is a prodrug that must be activated by the mycobacterial enzyme catalase-peroxidase KatG, after which it blocks the synthesis of mycolic acids, essential components of the mycobacterial cell wall. The compound was first synthesized in 1912 by Hans Meyer and Josef Mally at the German University in Prague, but its anti-tuberculosis value went unrecognized for decades; French physicians found nicotinamide had anti-tuberculosis activity in the 1940s, several laboratories independently identified isoniazid's effectiveness around 1950, and Roche launched its version, Rimifon, in 1952, with early clinical testing in the United States led by physician Walsh McDermott at Many Farms, Arizona.
Facts
Drug ClassAntibiotic (antitubercular prodrug) 1 Mechanism of ActionProdrug activated by catalase-peroxidase KatG that inhibits formation of the mycobacterial cell wall 1 Approved UseTreatment of tuberculosis 1 First Approved / Isolated Year Significant RiskVitamin B6 deficiency, liver toxicity, peripheral neuropathy and reduced blood cell production 1 Classification
Approval Status ATC ClassSourced to the subject's own accountJ: Antiinfectives for Systemic Use 2 Route of Administration WHO Essential MedicineSourced to the subject's own account FAQs
If isoniazid was first made in 1912, why did it take decades to become a tuberculosis treatment?
Its anti-tuberculosis activity was not discovered until the 1940s and 1950s, decades after the 1912 synthesis.
Hans Meyer and Josef Mally first synthesized the compound in 1912 at the German University in Prague, but nobody tested it against tuberculosis at the time, so its value went unrecognized. In the 1940s French physicians found that the related compound nicotinamide had anti-tuberculosis activity, which turned attention to this family of molecules. Around 1950 several laboratories independently identified isoniazid's effectiveness, and Roche launched its version, Rimifon, in 1952. Today it is used as a first-line treatment for latent and active tuberculosis infection.
Sources
1. Isoniazid (Wikipedia)
Lead section, paragraph 1, starting at character 0
Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the treatment of tuberculosis.
Lead section, paragraph 2, starting at character 0
Isoniazid is a prodrug that, when activated by catalase-peroxidase KatG, generates adducts and radicals that inhibit the formation of the mycobacterial cell wall.
Section: Tuberculosis, starting at character 0
The primary use of isoniazid is as first-line treatment for latent and active infection of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB).
Lead section, paragraph 3, starting at character 0
Although first synthesized in 1912, the anti-tuberculosis activity of isoniazid was not discovered until the 1940s.
Lead section, paragraph 2, starting at character 163
Side effects in those treated with isoniazid include vitamin B6 deficiency, liver toxicity, peripheral neuropathy, and a reduction in blood cell production.
https://en.wikipedia.org/wiki/Isoniazid, lead section
s M. avium, M. kansasii, and M. xenopi. It is usually taken by mouth, but may be used by injection into muscle.
- Regulatory approval status
View the Source2. Anatomical Therapeutic Chemical Classification System (Wikipedia)
WikipediaFirst-level anatomical group codes, Code JQuote, First-level anatomical group codes, Code J
Antiinfectives for systemic use
3. Wikipedia
Wikipedia contributors, Wikimedia Foundation
4. WHO Model List of Essential Medicines (Wikipedia)
WikipediaWHO Model List of Essential Medicines, Antituberculosis medicines sectionQuote, WHO Model List of Essential Medicines, Antituberculosis medicines section
Isoniazid
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