Novel MAO-B inhibitors. potential therapeutic use of the selective MAO-B inhibitor PF9601N in Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease that is characterized by preferential loss of dopaminergic neurons in the substantia nigra pars compacta, leading to declining levels of dopamine in the striatum. In our search for compounds able not only to extend the effects of dopamine by preventing its degradation but also to halt or slow the neurodegenerative process, we designed, synthesized, and biologically tested a series of propargylamines for their potential use as therapeutic agents for PD. Among them, PF9601N, [. N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], showed high potency and selectivity as a MAO-BI (monoamine oxidase type B inhibitor) and also demonstrated remarkable neuroprotective properties in several in vivo and cellular models of PD. In this chapter, we describe the preclinical evidence revealing the novel MAO-BI PF9601N as an interesting candidate for the treatment of PD. © 2011 Elsevier Inc.