MAO-B inhibitors for the treatment of Parkinson's disease

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 88 KB
• Volume: 17
• Category: Article
• ISSN: 0885-3185
• DOI: 10.1002/mds.5559

✦ Synopsis

INTRODUCTION BACKGROUND

Early attempts to enhance dopaminergic neurotransmission through inhibition of one of dopamine's major metabolizing enzyme -monoamine oxidase (MAO) -were made soon after the discovery of the striatal dopaminergic deficit and the efficacy of L-dopa. 1 However, side-effects ("cheese effect") associated with the non-selective type A plus B MAO inhibitors used in those days prevented further use. The development of selective MAO-B inhibitors through the work of Knoll et al. 2 on Selegiline, however, re-introduced the concept of MAO-inhibition into the therapy of Parkinson's disease. 3 RATIONALE MAO-B inhibition blocks the metabolism of dopamine and therefore could enhance both endogenous dopamine and dopamine produced from exogenously administrated Levodopa. Furthermore, MAO-B inhibitors block the conversion of MPTP to its active metabolic MPP + , which is a selective substantia nigra neurotoxin suggesting that this class of agents could have neuroprotective properties.