ISSN:
1420-908X
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Histamine methyltransferase from pig antrum mucosa was inhibited by 33 H1-receptor antagonists, by the H2-receptor antagonists burimamide and metiamide and by the burimamide analogue 5-methylburimamide, which did neither act on H1-nor on H2-receptors. Whereas all H1-receptor blocking agents as well as metiamide and 5-methylburimamide inhibited the enzyme in a competitive manner, the type of inhibition found for burimamide was a mixture of non-competitive and uncompetitive with respect to histamine, which is similar to that one observed with 1-methylhistamine, the product of the histamine methylation reaction. Furthermore, all compounds tested — with the only exception of burimamide — activated the gastric histamine methyltransferase in lower concentrations, the most potent activator being piprinhydrinate (180% increase of the enzyme activity). This enhancement of 1-methylhistamine formation by antihistaminic drugs was not due to a true activation of the enzyme by increasingV max, but was caused by partially abolishing the inhibition of histamine methyltransferase by so-called ‘optimum’ concentrations of histamine. Two explanations were given for the different mode of action of burimamide compared with that of metiamide and the other antihistaminic drugs: (1) The change in the type of inhibition from burimamide to metiamide seemed to be due to the introduction of a methylgroup into position 5 of the imidazole ring. (2) Burimamide and 1-, 2- and 3-methylhistamine were the only compounds tested in which the imidazole nucleus was substituted at position 4, but not at position 5, and which thus probably produced substrate or product inhibition.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01965724
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