Investigational agents in the treatment of Parkinson's disease: focus on safinamide.

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Malek NM, Grosset DG

Investigational agents in the treatment of Parkinson's disease: focus on safinamide.

J Exp Pharmacol. 2012 Aug 14;4:85-90. doi: 10.2147/JEP.S34343. eCollection 2012.

PubMed ID

27186120 [ View in PubMed

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Abstract

The authors review management issues in Parkinson's disease (PD) and provide an overview of the current pharmacological management strategies, with a specific focus on safinamide. Current therapeutic management of PD largely involves strategies to optimize the replacement of deficient dopamine, using levodopa, dopamine agonists, and inhibitors of dopamine-metabolizing enzymes. Currently under investigation for use in the treatment of PD, safinamide has multiple modes of action including monoamine oxidase B inhibition. It is well absorbed orally, has a long plasma half-life, and does not have liver enzyme-inducing or liver enzyme-inhibiting activity. Peak plasma concentration occurs 2-4 hours after single oral doses. Safinamide as monotherapy and as an adjunct to dopamine agonists improves Unified Parkinson's Disease Rating Scale motor scores. One randomized, placebo-controlled trial involving 168 patients given a median safinamide dose of 70 mg/day (range 40-90 mg/day) significantly increased the proportion of responders - defined as patients improving their Unified Parkinson's Disease Rating Scale motor scores by 30% or more from baseline - after 3 months (37.5% for safinamide versus 21.4% for placebo; P < 0.05). Safinamide increased "on" time with no or minor dyskinesia compared with the placebo in another trial, but dyskinesia severity was not reduced. Safinamide was well tolerated, with an adverse effect profile similar to that of the placebo. Further Phase III trial data for safinamide efficacy is awaited, and will be of interest in a comparison with other developments in PD therapeutics: modified formulations of available compounds, new drug classes such as adenosine receptor antagonists, and gene-based therapies.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Safinamide	Cytochrome P450 2C19	Protein	Humans	Unknown	Inhibitor	Details