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 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.