Effects of the histamine H3 agonist (R)-alpha-methylhistamine and the antagonist thioperamide in vitro on monoamine oxidase activity in the rat brain.
The effects of an H3 agonist, (R)-alpha-methylhistamine (alpha-MeHA), and an H3 antagonist, thioperamide, on monoamine oxidase (MAO) activity in rat hypothalamus were studied in vitro. Thioperamide was more potent in inhibiting MAO-B than MAO-A activity; MAO-B activity in rat hypothalamic homogenates was competitively inhibited by thioperamide with a Ki value of 175 micronM. From this in vitro experiment, the conversion of N-telemethylhistamine to N-tele-methylimidazoleacetic acid may be inhibited by thioperamide, suggesting that thioperamide may affect the regulation of histamine metabolism within histaminergic neurons. In contrast with the results obtained with thioperamide, alpha-MeHA inhibited MAO-A more potently than MAO-B activity; the Ki values for MAO-A and -B of hypothalamic homogenates were estimated to be 1.1 and 3.3 mM, respectively. The weak inhibitory effect of alpha-MeHA for MAO-B does not seem to be a major cause of changes in N-tele-methylhistamine concentrations.
Sakurai
E
E
Department of Pharmaceutics I, Tohoku College of Pharmacy, Sendai, Japan.
Sakurai
E
E
Maeyama
K
K
Watanabe
T
T
Jossan
S S
SS
Oreland
L
L
D000818:Animals; D001921:Brain / Q000201:enzymology*; D017442:Histamine Agonists / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000187:drug effects* / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; C069357:alpha-methylhistamine; D008995:Monoamine Oxidase; C052075:thioperamide