Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 327, Issue 4, pp 273–278

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

Authors

  • Märit Eriksson
    • Research and Development LaboratoriesAstra Läkemedel AB
  • Christopher J. Fowler
    • Research and Development LaboratoriesAstra Läkemedel AB
Article

DOI: 10.1007/BF00506236

Cite this article as:
Eriksson, M. & Fowler, C.J. Naunyn-Schmiedeberg's Arch. Pharmacol. (1984) 327: 273. doi:10.1007/BF00506236

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 i slope 1.4 μmol/l, K i int 24 μmol/l) and of SSAO (K i slope 12 μmol/l, K i int 6 μmol/l).

Key words

Monoamine oxidase Benzylamine Mexiletine Clorgyline Amine oxidase Semicarbazide

Copyright information

© Springer-Verlag 1984