Leflunomide, a Reversible Monoamine Oxidase Inhibitor

Title:Leflunomide, a Reversible Monoamine Oxidase Inhibitor

Volume: 16 Issue: 2

Author(s): Jacobus P. Petzer and Anél Petzer

Affiliation:

Keywords: Leflunomide, isoxazole, monoamine oxidase, MAO, inhibition, reversible.

Abstract: A screening study aimed at identifying inhibitors of the enzyme, monoamine oxidase (MAO), among clinically used drugs have indicated that the antirheumatic drug, leflunomide, is an inhibitor of both MAO isoforms. Leflunomide inhibits human MAO-A and MAO-B and exhibits IC₅₀ values of 19.1 μM and 13.7 μM, respectively. The corresponding K_i values are 17.7 μM (MAO-A) and 10.1 μM (MAO-B). Dialyses of mixtures of the MAO enzymes and leflunomide show that inhibition of the MAOs by leflunomide is reversible. The principal metabolite of leflunomide, teriflunomide (A77 1726), in contrast is not an MAO inhibitor. This study concludes that, although leflunomide is only moderately potent as an MAO inhibitor, isoxazole derivatives may represent a general class of MAO inhibitors and this heterocycle may find application in MAO inhibitor design. In this respect, MAO inhibitors are used in the clinic for the treatment of depressive illness and Parkinson’s disease, and are under investigation as therapy for certain types of cancer, Alzheimer’s disease and age-related impairment of cardiac function.

Cite this article as:

P. Petzer Jacobus and Petzer Anél, Leflunomide, a Reversible Monoamine Oxidase Inhibitor, Central Nervous System Agents in Medicinal Chemistry 2016; 16 (2) . https://dx.doi.org/10.2174/1871524915666150824154329