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Inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by mexiletine and related compounds

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Summary

The in vitro inhibition by mexiletine and related compounds of the activity of rat brain, heart and lung mono-amine 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 μmol/l and 320 μmol/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 (K slopei 1.4 μmol/l, K inti 24 μmol/l) and of SSAO (K slopei 12 μmol/l, K inti 6 μmol/l).

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Author notes

  1. Märit Eriksson

    Present address: Central Laboratories, Apoteksbolaget, S-171 03, Solna, Sweden

Authors and Affiliations

  1. Research and Development Laboratories, Astra Läkemedel AB, S-151 85, Södertälje, Sweden

    Märit Eriksson & Christopher J. Fowler

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  1. Märit Eriksson
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  2. Christopher J. Fowler
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Eriksson, M., Fowler, C.J. Inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by mexiletine and related compounds. Naunyn-Schmiedeberg's Arch. Pharmacol. 327, 273–278 (1984). https://doi.org/10.1007/BF00506236

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  • DOI: https://doi.org/10.1007/BF00506236

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