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).