Although not used as extensively as other antidepressants for the treatment of depression, the monoamine oxidase (MAO) inhibitors continue to hold a niche in psychiatry and to have a relatively broad spectrum with regard to treatment of psychiatric and neurological disorders. Experimental and clinical research on MAO inhibitors has been expanding in the past few years, primarily because of exciting findings indicating that these drugs have neuroprotective properties (often independently of their ability to inhibit MAO). The non-selective and irreversible MAO inhibitors tranylcypromine (TCP) and phenelzine (PLZ) have demonstrated neuroprotective properties in numerous studies targeting elements of apoptotic cascades and neurogenesis. l-Deprenyl and rasagiline, both selective MAO-B inhibitors, are used in the management of Parkinson's disease, but these drugs may be useful in the treatment of other neurodegenerative disorders given that they demonstrate neuroprotective/neurorescue properties in a wide variety of models in vitro and in vivo. Although the focus of studies on the involvement of MAO inhibitors in neuroprotection has been on MAO-B inhibitors, there is a growing body of evidence demonstrating that MAO-A inhibitors may also have neuroprotective properties. In addition to MAO inhibition, PLZ also inhibits primary amine oxidase (PrAO), an enzyme implicated in the etiology of Alzheimer's disease, diabetes and cardiovascular disease. These multifaceted aspects of amine oxidase inhibitors and some of their metabolites are reviewed herein.Highlights
▪ Many MAOIs exert protective effects via mechanisms independent of MAO inhibition. ▪ Alternate protective mechanisms include increased GABA and aldehyde sequestration. ▪ MAOIs may reduce cell loss in AD, PD, ischemia and other degenerative conditions. ▪ Protective or harmful effects of MAOI metabolites should be considered.