Recent advances in Parkinson's disease therapy: use of monoamine oxidase inhibitors.
Monoamine oxidase inhibitors inhibit dopamine metabolism and are therefore effective in treating Parkinson's disease, a condition associated with progressive striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra. Selegiline is currently the most widely used monoamine oxidase-B inhibitor for Parkinson's disease, but has a low and variable bioavailability, and is metabolized to L-methamphetamine and L-amphetamine that carry a risk for potential neurotoxicity. There are two new approaches that circumvent these potential disadvantages. First, selegiline orally disintegrating tablets provide a novel delivery form of selegiline, avoiding first pass metabolism by rapid absorption through the oral mucosa, thus leading to significantly lower plasma concentrations of L-metamphetamine and L-amphetamine. Selegiline orally disintegrating tablets prove to be clinically effective and safe in patients with moderately advanced Parkinson's disease. Second, rasagiline is a new monoamine oxidase inhibitor, without known neurotoxic metabolites. In large clinical trials, rasagiline proves effective as monotherapy in early Parkinson's disease, as well as adjunctive therapy to levodopa in advanced disease. Clinical data suggest, in addition, a disease-modifying effect of rasagiline that may correlate with neuroprotective activity of monoamine oxidase-B inhibitors in animal models of Parkinson's disease.
Henchcliffe
Claire
C
Weill Medical College of Cornell University, Department of Neurology and Neuroscience, 428 East 72, Street, Suite 400, NY 10021, USA. clh2007@med.cornell.edu
Schumacher
H Christian
HC
Burgut
F Tuna
FT
D000978:Antiparkinson Agents / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D004035:Diet Therapy / Q000379:methods; D015259:Dopamine Agents / Q000627:therapeutic use; D004341:Drug Evaluation; D004347:Drug Interactions; D005104:Expert Testimony; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D007980:Levodopa / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*; D012642:Selegiline / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*
D000978:Antiparkinson Agents; D015259:Dopamine Agents; D007189:Indans; D008996:Monoamine Oxidase Inhibitors; C031967:rasagiline; D012642:Selegiline; D007980:Levodopa