Inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by mexiletine and related compounds.
The in vitro inhibition by mexiletine and related compounds of the activity of rat brain, heart and lung monoamine oxidase-A (MAO-A), rat brain MAO-B, human platelet-poor plasma benzylamine oxidase and a clorgyline-resistant, semicarbazide-sensitive amine oxidase (SSAO) distinct from both MAO and benzylamine oxidase has been studied. The compounds were most active towards MAO-A and SSAO. IC50 values for mexiletine towards rat heart MAO-A and SSAO were 10 mumol/l and 320 mumol/l, respectively. Replacement of the para-hydrogen atom in the mexiletine aromatic ring by bromine increased potency towards both MAO-A and SSAO. Replacement of the ortho-methyl group in the mexiletine aromatic ring by hydrogen increased the potency towards SSAO alone. FLA 1042, with both these substitutions, was found to be a reversible mixed-type inhibitor of both MAO-A (Kislopei 1.4 mumol/l, Kiinti 24 mumol/l) and of SSAO (Kislopei 12 mumol/l, Kiinti 6 mumol/l).
D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D001595:Benzylamine Oxidase / Q000037:antagonists & inhibitors; D001792:Blood Platelets / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D003010:Clorgyline / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009206:Myocardium / Q000201:enzymology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012663:Semicarbazides / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D011437:Propylamines; D012663:Semicarbazides; D008801:Mexiletine; D012701:Serotonin; D001595:Benzylamine Oxidase; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors; D003010:Clorgyline