Inhibition of amine oxidases by the histamine-1 receptor antagonist hydroxyzine.
The effects of the drug hydroxyzine on the activities of the rat liver monoamine oxidases (EC 1.4.3.6; MAO) and the membrane-bound and soluble forms of bovine semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) were studied. Hydroxyzine was found to be a competitive inhibitor of MAO-B (Ki - 38 microM), whereas it had a low potency towards MAO-A (IC50 > 630 microM). Although it was a relatively potent competitive inhibitor of bovine plasma SSAO (Ki approximately 1.5 microM), it was a weak inhibitor of the membrane-bound form of the enzyme from bovine lung (IC50 approximately 1 mM). These findings extend our knowledge of the drug binding capabilities of the amine oxidases and suggest that these interactions may contribute to the complex actions of this drug.
O'Sullivan
J
J
Department of Biochemistry, Trinity College, Dublin, Ireland. josulli@tcd.ie
O'Sullivan
M I
MI
Tipton
K E
KE
Davey
G
G
D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects*; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006919:Hydroxyzine / Q000493:pharmacokinetics / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007554:Isotopes / Q000493:pharmacokinetics; D008099:Liver / Q000737:chemistry; D008995:Monoamine Oxidase / Q000378:metabolism*; D010949:Plasma / Q000737:chemistry; D051381:Rats
D001596:Benzylamines; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D007554:Isotopes; D006919:Hydroxyzine; C030796:benzylamine; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase