Safinamide for the treatment of Parkinson’s disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease caused by a complex interaction of loss of dopaminergic and non-dopaminergic neurotransmitter systems. Drugs acting on the dopaminergic pathways are the mainstay of treatment for motor symptoms today. Safinamide (NW-1015) is a novel drug with multiple actions. It is a monoamine oxidase B inhibitor and improves dopaminergic transmission. In addition, it has antiglutamatergic effects and can thus reduce dyskinesias, which is a side effect limiting most dopaminergic therapy. In Phase III trials, safinamide has been found to be a useful adjunctive to dopamine agonists in early PD and has been shown to increase time without increasing troublesome dyskinesias when used as an adjunct to levodopa in patients with advanced PD. A possible neuroprotective role in inhibiting PD disease progression is envisaged and warrants future studies.

Keywords::

• add-on therapy
• antiglutamatergic
• early and late disease
• monoamine oxidase B inhibitor
• Parkinson’s disease

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Safinamide is a new monoamine-oxidase B inhibitor that has been found to be useful adjunctive to dopamine agonists and levodopa-carbidopa in early and late Parkinson’s disease (PD) and is awaiting the US FDA approval.

• Its favorable pharmacokinetics and pharmacodynamics makes it possible for a once-daily oral dosing.

• Safinamide blocks sodium and calcium channels and inhibits sigma-1 receptors, making it a putative antiepileptic.

• The sodium channel blockade stops glutamate release at NMDA receptors and has been shown to reduce dyskinesias in animal models.

• In PD trials, addition of safinamide has improved both motor scores and duration of ‘on’ similar to other monoamine-oxidase B inhibitors, with an added benefit of not increasing troublesome dyskinesias.

• Safinamide has shown to improve depression and in a single substudy has shown to improve cognitive functions.

• A possible neuroprotective role in inhibiting PD disease progression is envisaged.

• Future studies are warranted to elicit the antidyskinetic and neuroprotective effects of safinamide.