title: Methyl derivatives of histamine; interaction with histamine metabolism.
abstract: Several histamine analogs, with ring or side chain methyl groups, were tested for interaction with certain aspects of 14C-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 didney, while 2-methylhistamine was most effective. None of the drugs showed a significant effect on in vivo formation of 14C-histamine by mouse stomach. All analogs had a definite effect on the distribution and fate of intravenously injected 14C-histamine. The 2-methyl analog was the strongest in vivo inhibitor of histamine methylation, and 3-methylhistamine next. The side chain N-methylated histamies altered uptake of 14C-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.
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004347:Drug Interactions; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006632:Histamine / Q000378:metabolism*; D006637:Histamine N-Methyltransferase / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008761:Methylhistamines / Q000494:pharmacology*; D051379:Mice; D013270:Stomach / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D008761:Methylhistamines; D006632:Histamine; D006637:Histamine N-Methyltransferase