Effects of histamine H3-receptor ligands on brain monoamine oxidase in various mammalian species

Brain Res. 2001 Jul 6;906(1-2):180-3. doi: 10.1016/s0006-8993(01)02396-4.

Abstract

The effects of an H3 agonist, R-alpha-methylhistamine (alpha-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, alpha-MeHA inhibited MAO-A more potently than MAO-B at high concentrations in all three species. The K(i) values for MAO-A of alpha-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 alpha-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 microM, 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.

MeSH terms

  • Aged
  • Animals
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • Dose-Response Relationship, Drug
  • Histamine / metabolism
  • Histamine Agonists / pharmacology*
  • Histamine Antagonists / pharmacology*
  • Humans
  • Hypothalamus / drug effects*
  • Hypothalamus / enzymology
  • Imidazoles / metabolism
  • Ligands
  • Macaca
  • Methylhistamines / metabolism
  • Methylhistamines / pharmacology
  • Middle Aged
  • Monoamine Oxidase / drug effects*
  • Monoamine Oxidase / metabolism
  • Neurons / drug effects*
  • Neurons / enzymology
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Histamine H3 / drug effects*
  • Receptors, Histamine H3 / metabolism
  • Subcellular Fractions / drug effects*
  • Subcellular Fractions / enzymology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Histamine Agonists
  • Histamine Antagonists
  • Imidazoles
  • Ligands
  • Methylhistamines
  • Piperidines
  • Receptors, Histamine H3
  • methylimidazoleacetic acid
  • alpha-methylhistamine
  • Histamine
  • Monoamine Oxidase
  • thioperamide
  • tele-methylhistamine