Monoamine oxidase-B inhibition in the treatment of Parkinson's disease.
Inhibitors of monoamine oxidase (MAO) with selectivity and specificity for MAO type B prolong the activity of both endogenously and exogenously derived dopamine, making them an option either as monotherapy in early Parkinson's disease or as adjunctive therapy in patients treated with levodopa who are experiencing motor complications. In addition to symptomatic benefits, experimental data suggest that MAO-B inhibitors may be neuroprotective through MAO-B inhibition and other mechanisms that have yet to be clearly defined. The two available MAO-B inhibitors approved for use in the United States, rasagiline and selegiline, each provide symptomatic relief as monotherapy and as adjunctive therapy, and have shown potential disease-modifying effects in experimental models and clinical studies. Selegiline in a conventional tablet formulation is less bioavailable than rasagiline, resulting in limited potency. It also has amphetamine metabolites that may produce adverse effects and interfere with any putative disease-modifying effects. The oral disintegrating tablet formulation of selegiline allows pregastric absorption, minimizing first-pass metabolism, thereby increasing selegiline bioavailability and reducing the concentration of amphetamine metabolites. Rasagiline, more potent than selegiline, exhibits disease-modifying effects in experimental models and lacks amphetamine metabolites. Both the symptomatic and potential disease-modifying effects of rasagiline are under investigation. A third agent with MAO-B inhibition properties, safinamide, is in phase III development. Although not yet approved, safinamide may offer the added advantage of combined MAO-B and dopamine reuptake inhibition.
Movement Disorders Center, University of Florida, McKnight Brain Institute, Gainesville, FL 32610, USA. fernandez@neurology.ufl.edu
Hubert H
HH
Fernandez
Jack J
JJ
Chen
D000409:Alanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use; D018491:Dopamine Agonists / Q000627:therapeutic use; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D007980:Levodopa / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000627:therapeutic use
D000978:Antiparkinson Agents; D001596:Benzylamines; D018491:Dopamine Agonists; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D012642:Selegiline; D007980:Levodopa; C092797:safinamide; D000409:Alanine