Current status of safinamide for the drug portfolio of Parkinson’s disease therapy

Abstract

Parkinson’s disease (PD) is characterized by a slowly ongoing neuronal death. This alters dopaminergic and glutamatergic neurotransmission and causes a wide variety of motor and non-motor features. Safinamide has a unique pharmacological profile, which combines modulation of dopamine metabolism by reversible, highly specific monoamine oxidase-B inhibition, blockage of voltage-dependent sodium channels, modulation of calcium channels and of glutamate release induced by abnormal neuronal activity. Therefore, safinamide represents an ideal candidate for the treatment of PD. This compound asks for one time daily intake only within an optimum dose range between 50 and 100 mg. In clinical trials, safinamide was well tolerated and safe, improved motor behavior even in combination with dopamine agonist only, ameliorated levodopa-associated motor complications. Safinamide has the potential to become an important compound for the therapy of PD, since its symptomatic efficacy appears to be superior to available monoamine oxidase-B inhibitors or N-methyl-d-aspartate receptor antagonists like amantadine, according to available trial outcomes.

Keywords::

• amantadine
• dopamine substitution
• glutamate
• MAO-B inhibition
• NMDA antagonism
• Parkinson’s disease
• rasagiline
• safinamide
• seligiline

Financial & competing interests disclosure

T Müller has participated in advisory boards for the safinamide studies and served as a principal investigator. The author has no other 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 apart from those disclosed.

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

Key issues

• • Safinamide is a highly selective and reversible inhibitor of monoamine oxidase-B that increases levels of available dopamine in the synaptic cleft.

• • Safinamide blocks sodium channels and modulates of Ca²⁺ channels, which modulate the release of glutamate.

• • This unique pharmacological profile suggests safinamide as an ideal candidate for the treatment of motor and non-motor features of Parkinson’s disease, which is predominantly characterized by altered dopaminergic and glutamatergic neurotransmission.

• • Safinamide was effective as an adjunct to dopamine agonist monotherapy, was well tolerated and safe within an optimum dose range of 50–100 mg/day.

• • Safinamide improved levodopa-associated off-phenomena in more advanced Parkinson's disease patients.