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Structural requirements of imidazole compounds to be inhibitors or activators of histamine methyltransferase: Investigation of histamine analogues and H2-receptor antagonists

  • Selected Papers Given at the ‘6th Annual Meeting of the European Branch of the Histamine Club’, London, 20–22 April, 1977
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Abstract

The influence of imidazole compounds (histamine analogues and H2-receptor antagonists) and of the specific histamine H2-receptor agonist dimaprit on histamine methyltransferase (HMT) from pig gastric mucosa was investigated.

By their effect on HMT two groups of substituted imidazole compounds could be differentiated. Some were pure inhibitors of the enzyme, whereas others were inhibitors only in high concentrations (>10−3 M) and activators of the enzyme in low concentrations. The strongest inhibitor of all the histamine analogues tested was 2-methylhistamine (I.D.50=0.6×10−4 M), whereas the strongest activation was exerted by 4-[(2-amino-ethylmercapto)-methyl]-5-methylimidazole (57% increase of enzymic activity at 10−4 M concentration). From the group of histamine H2-receptor antagonists only burimamide was an inhibitor (I.D.50=1.6×10−4 M) whereas metiamide and cimetidine belonged to the strongest activators of the enzyme (179% enzymic activity at 10−4 M concentration of metiamide).

The strongest activator of all the substances tested in this series of compounds, however, was the non-imidazole compound dimaprit, which increased enzymic activity by 86% in as small a concentration as 10−5 M.

For substituted imidazole ring systems an attempt is made to evaluate the structural requirements of the single compound to classify it as a pure inhibitor or a concentration-dependent inhibitor/activator of HMT.

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  1. Division of Experimental Surgery and Pathological Biochemistry, Surgical Department of the University, Robert-Koch-Straße 8, D-3550, Marburg, Federal Republic of Germany

    H. Barth & W. Lorenz

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  1. H. Barth
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Dedicated to Prof. Dr Dr E. Werle (†) on the occasion of his 75th birthday.

Supported by grant Lo 199/7 from Deutsche Forschungsgemeinschaft.

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Barth, H., Lorenz, W. Structural requirements of imidazole compounds to be inhibitors or activators of histamine methyltransferase: Investigation of histamine analogues and H2-receptor antagonists. Agents and Actions 8, 359–365 (1978). https://doi.org/10.1007/BF01968615

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  • DOI: https://doi.org/10.1007/BF01968615

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