Porphyrinuric action of drugs related to sulphanilamide. Comparison with reported toxicity, therapeutic efficiency and causation of methaemoglobinaemia. Definition of the structure responsible for porphyrinuric action

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Abstract
]The finding that sulphanilamide, when administered to rats, increases urinary and fecal porphyrin excretion, was amplified by extending the investigation to include other drugs of the sulphonamide series and also simpler related chemical substances. Within the series of sulphonamide drugs tested, no quantitative relation was found between therapeutic efficiency and porphyrinuric action. Porphyrinuric action ran roughly parallel with general toxicity. In general, substances which exerted a porphyrinuric action also produced methemoglobinemia. The chemical grouping necessary for increasing porphyrin excretion may therefore be defined in the same terms as allotted to the structure giving rise of methemoglobin forma-tion[long dash]viz., the presence of an aromatic amino group, un-substituted or potentially free and preferably situated in such a system that it can undergo oxidation with the formation of a hydroxylamine derivative or a reversibly oxidizing system such as p- or o-iminoquinone.[long dash]The last generalization is discussed in the light of Heubner''s work on the mechanism of methemoglobin formation following administration of aniline. Both aniline and nitrobenzene (which can undergo reduction in vivo) are effective porphyrinuric agents; this may be important in connection with the control of the health of industrial workers .[long dash]The evidence that sulphanilamide, etc., may to some extent undergo oxidation at the amino group in vivo is considered. The extra coproporphyrin III excreted after administration of these substances may be derived from an increased breakdown of blood pigment. Methemoglobin, when once formed, is perhaps degraded, in part.at least, by a mechanism which leads ultimately not to bile'' pigment but to porphyrin. Hematin may possibly represent one of the intermediary stages in this transformation.