alexa Methotrexate: from its introduction to non-oncologic therapeutics to anti-TNF-α.
Toxicology

Toxicology

Journal of Drug Metabolism & Toxicology

Author(s): Benedek TG, Benedek TG

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Abstract The history of the rheumatologic use of methotrexate until the 1990s will be reviewed, beginning with its pharmacology, with the focus on rheumatoid arthritis (RA). The insufficient availability of cortisone in the 1950s as well as the early recognition of its potential toxicity stimulated searches for alternative anti-inflammatory drugs. Two related derivatives of folic acid, aminopterin and amethopterin (MTX,) were found to give rapid symptomatic relief in cases of psoriasis vulgaris and psoriatic arthritis. For several years MTX was used primarily to treat psoriasis, and the dermatologic treatment protocols came to be used by rheumatologists. Giving MTX weekly rather than daily was found to diminish the risk of toxic effects. MTX became favoured over cyclophosphamide because of its lack of carcinogenicity, and although azathioprine lacked the hepatotoxicity of MTX, its anti-rheumatic effects were considered to be somewhat weaker. Although trials of MTX for the treatment of severe RA began in the 1960s, the first placebo-controlled study of MTX in RA was reported in 1985 and a comparison with Myochrysine in 1987. MTX has replaced gold compounds because it has been found to be more rapidly effective and better tolerated. The mechanisms of its anti-rheumatic effects remain incompletely explained, as are explanations of instances of its failure. Its recent use in combination with anti-TNFα agents appears to be another therapeutic advance.
This article was published in Clin Exp Rheumatol and referenced in Journal of Drug Metabolism & Toxicology

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