Interactions of monoamine oxidases with the antiepileptic drug zonisamide: specificity of inhibition and structure of the human monoamine oxidase B complex

J Med Chem. 2011 Feb 10;54(3):909-12. doi: 10.1021/jm101359c. Epub 2010 Dec 22.

Abstract

The binding of zonisamide to purified, recombinant monoamine oxidases (MAOs) has been investigated. It is a competitive inhibitor of human MAO B (K(i) = 3.1 ± 0.3 μM), of rat MAO B (K(i) = 2.9 ± 0.5 μM), and of zebrafish MAO (K(i) = 30.8 ± 5.3 μM). No inhibition is observed with purified human or rat MAO A. The 1.8 Å structure of the MAO B complex demonstrates that it binds within the substrate cavity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / chemistry*
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Isoxazoles / chemistry*
  • Models, Molecular
  • Monoamine Oxidase / chemistry*
  • Monoamine Oxidase Inhibitors / chemistry*
  • Protein Binding
  • Protein Conformation
  • Rats
  • Zonisamide

Substances

  • Anticonvulsants
  • Isoxazoles
  • Monoamine Oxidase Inhibitors
  • Zonisamide
  • Monoamine Oxidase

Associated data

  • PDB/3PO7