New Therapeutic Strategies in Parkinson’s Disease: Inhibition of MAO-B by Ro 19-6327 and of COMT by Ro 40-7592

摘要: About three decades ago, it was observed for the first time that DOPA (levodopa, 3,4-dihydroxyphenyl-L-alanine) dramatically improved akinetic Parkinson’s patients1. Several direct acting dopamine (DA) D2 agonists were subsequently investigated but none proved to be sufficiently effective used routinely as sole agent in control of motor fluctuations disease (PD). Motor also frequently complicate therapy and limit its therapeutic benefit. When adjuvants DOPA, DA may modestly diminish fluctuations, a relatively high incidence side-effects, chiefly psychotoxic, has limited their use2. It is noteworthy chronic treatment PD with devoid neurotoxic effects does not produce damage nigro-striatal dopaminergic neurones3. Therefore, combination peripheral L-amino acid decarboxylase (AADC) inhibitors will remain standard pharmacological at least next decade. However, new strategies are being actively some have been proposed ameliorate dyskinesias occurring patients under combined AADC inhibitor, e.g. benserazide (Madopar®) or carbidopa (Sinemet®)2.