Methyl derivatives of histamine; Interaction with histamine metabolism

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Abstract
Several histamine analogs, with ring or side chain methyl groups, were tested for interaction with certain aspects of14C-histamine metabolism. The physiological catabolite, denoted as 3-methylhistamine under the nomenclature we have adopted, is known to inhibit histamine methylation in vitro and in vivo. At low concentrations, all analogs inhibited histamine methylation by mouse brain homogenates; however 3-methylhistamine was completely ineffective against the highly active enzyme from rat kidney, while 2-methylhistamine was most effective. None of the drugs showed a significant effect on in vivo formation of14C-histamine by mouse stomach. All analogs had a definite effect on the distribution and fate of intravenously injected14C-histamine. The 2-methyl analog was the strongest in vivo inhibitor of histamine methylation, and 3-methylhistamine next. The side chain N-methylated histamines altered uptake of14C-histamine in some tissues but inhibited methylation weakly, if at all. Data on blood, kidney and urine for 4-methylhistamine were unique, and suggested some effect on tubular reabsorption. 2-methylhistamine may prove to be the inhibitor of choice for in vivo studies on histamine methylation.