Interactions of Monoamine Oxidases with the Antiepileptic Drug Zonisamide: Specificity of Inhibition and Structure of the Human Monoamine Oxidase B Complex

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 mu M), of rat MAO B (K-i = 2.9 +/- 0.5 mu M), and of zebrafish MAO (K-i = 30.8 +/- 5.3 mu M). No inhibition is observed with purified human or rat MAO A. The 1.8 angstrom structure of the MAO B complex demonstrates that it binds within the substrate cavity.