REQUIREMENTS FOR ACTIVITY OF CERTAIN ‘SPECIFIC’ ANTIRHEUMATIC DRUGS: MORE THAN A SIMPLE THIOL GROUP?

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Abstract
The relationship between chemical structure and the clinical activity and toxicity of several second-line antirheumatic drugs is examined. The presence of a thiol group in many of these agents has previously been noted, but most of the compounds additionally either possess, or form metabolites containing, the ethanethiol backbone or a similar ring structure. This applies not only to penicillamine and disodium aurothiomalate but also to thiola, 5-thiopyridoxine, levamisole and captopril. The presence of free circulating thiols has recently been shown for several of these compounds including free thiomalate in the case of disodium aurothiomalate, which on a molar basis is the most potent agent of all. Further study of thiomalate and related compounds in vitro and in vivo may clarify the pathogenesis of rheumatoid arthritis as well as allowing the development of more effective and less toxic second-line agents.

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