K. Netter, K. Bodenschatz
Aug 1, 1967
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0
Influential Citations
33
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Quality indicators
Journal
Biochemical pharmacology
Abstract
Abstract N -methylation of histamine by imidazole - N -methyl transferase can be inhibited in vitro by antihistamines of the benzimidazole and ethylene diamine types. Clemizole and tripelennamine as well as some of their derivatives were used in this study. Rat kidney homogenate served as enzyme source. In final concentrations of 2.5 × 10 −4 M both groups of antihistamines inhibit by about 50 per cent. From a Lineweaver-Burk plot the inhibition appears to be competitive. In accordance with observations on other series of drugs the inhibitory activity is higher when the hydrogen in para-position of a benzyl group is substituted by halogens, activity rising in that order: H, Cl, Br. The effect of these antihistamines does not seem to be mediated through their interaction with functional sulfhydryl groups. In vivo blocking of histamine N -methylation cannot be achieved because of the toxicity of the antihistamines at the required dosage. Attempts to deplete the animals of activated methyl groups by large doses of nicotinamide and to produce an ‘amethylosis’ were unsuccessful.