Abstract
BURIMAMIDE has been shown to antagonise the effects of histamine on isolated cardiac and uterine muscle in vitro, and to antagonise histamine-stimulated acid secretion in vivo in animals and in man1. This pattern of pharmacological effects is not achieved by conventional, tertiary amine, anti-histaminic drugs (of which mepyramine is typical) and has led to the definition of burimamide as an H2-receptor antagonist1 and mepyramine as an H1-receptor antagonist2. Although burimamide was pharmacologically sufficiently active to allow for definition of its properties in man3 it seemed to lack the combination of high specific activity with adequate oral bioavailability needed for exploring the therapeutic potential of this new type of drug action. Attempts to produce a more suitable drug were based on the observation that burimamide is a competitive antagonist to histamine and that both compounds possess imidazole rings, We therefore compared the relative species populations of the respective rings and modified the burimamide structure so as to increase the equilibrium concentration of imidazole species considered most likely to be active.
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BLACK, J., DURANT, G., EMMETT, J. et al. Sulphur-methylene isosterism in the developent of metiamide, a new histamine H2-receptor antagonist. Nature 248, 65–67 (1974). https://doi.org/10.1038/248065a0
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DOI: https://doi.org/10.1038/248065a0
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