Different Generations of Type-B Monoamine Oxidase Inhibitors in Parkinson's Disease: From Bench to Bedside

Current Neuropharmacology
Marika Alborghetti, Ferdinando Nicoletti

Abstract

Three inhibitors of type-B monoamine oxidase (MAOB), selegiline, rasagiline, and safinamide, are used for the treatment of Parkinson's disease (PD). All three drugs improve motor signs of PD, and are effective in reducing motor fluctuations in patients undergoing long-term L-DOPA treatment. The effect of MAOB inhibitors on non-motor symptoms is not uniform and may not be class-related. Selegiline and rasagiline are irreversible inhibitors forming a covalent bond within the active site of MAOB. In contrast, safinamide is a reversible MAOB inhibitor, and also inhibits voltage- sensitive sodium channels and glutamate release. Safinamide is the prototype of a new generation of multi-active MAOB inhibitors, which includes the antiepileptic drug, zonisamide. Inhibition of MAOB-mediated dopamine metabolism largely accounts for the antiparkinsonian effect of the three drugs. Dopamine metabolism by MAOB generates reactive oxygen species, which contribute to nigro-striatal degeneration. Among all antiparkinsonian agents, MAOB inhibitors are those with the greatest neuroprotective potential because of inhibition of dopamine metabolism, induction of neurotrophic factors, and, in the case of safinamide, inhibition of glutamate release. The ...Continue Reading

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Citations

Jul 19, 2020·Aging Clinical and Experimental Research·Domiziana RinaldiFrancesco E Pontieri
Aug 14, 2020·CNS Drugs·Paulina Gonzalez-LatapiSusan H Fox
Oct 18, 2020·Journal of Neural Transmission·Domiziana RinaldiFrancesco E Pontieri
Jan 21, 2021·British Journal of Haematology·Betty S PaceAbdullah Kutlar
Dec 17, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Rona R RamsaySalvatore Guccione
Jan 10, 2021·Brain Sciences·Ana Gómez-LópezAraceli Alonso-Canovas
Jan 8, 2021·Frontiers in Neuroscience·Chengqian LiAnmu Xie
Jan 8, 2021·Stem Cell Research & Therapy·Zhuangzhuang XiaoHongwu Du
Feb 14, 2021·Medicine·Yingtan WangGuanglei Xun
Jun 19, 2021·Neurological Research·Edoardo BianchiniFrancesco E Pontieri
Aug 11, 2021·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Massimiliano PlastinoDomenico Bosco
Jan 30, 2022·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Chun CuiYan-Qin Shen

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