Abstract
The effects of an H3 agonist, R-α-methylhistamine (α-MeHA), and an H3 antagonist, thioperamide, on monoamine oxidase (MAO) activity in the hypothalamus of rat, monkey and human brains were compared in vitro. The histamine H 3-receptor ligands competitively inhibited MAO-B, but noncompetitively inhibited MAO-A in all three mammalian species. However, α-MeHA inhibited MAO-A more potently than MAO-B at high concentrations in all three species. The K i values for MAO-A of α-MeHA in hypothalamic homogenates of rat, monkey and human brains were estimated to be 1.1, 1.2 and 1.9 mM, respectively, suggesting that α-MeHA cannot behave as a substrate for the MAO inhibitor. In contrast, rat, monkey and human brain MAO-B activities were inhibited by thioperamide, with respective K i values of 174.6, 8.2 and 10.8 μM, more potently than MAO-A activity. These results indicate that thioperamide, which elicits a strong activation of histamine release and turnover to N-tele-methylhistamine from histamine, competitively inhibits the conversion of N-tele-methylhistamine to N-tele-methylimidazoleacetic acid in human and monkey brains where MAO-B predominates.
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