Safinamide - a unique treatment targeting both dopaminergic and non-dopaminergic systems

Abstract

Dopaminergic replacement therapies are prescribed widely to improve motor problems in Parkinson's disease (PD). However, as the disease progresses, the response to levodopa (l-dopa) doses becomes shorter and patients experience symptom recurrence at the end of the dose effect. These so-called OFF periods may become refractory to treatment, and may become associated with disabling motor fluctuations or dyskinesias. In addition to dopamine, glutamate excitotoxicity, resulting from disturbance of the homeostatic balance of neurotransmitters and elevated extracellular levels of glutamate, is potentially an important therapeutic target. Safinamide has been investigated in phase III clinical trials as adjunct therapy to l-dopa in mid- to late-stage fluctuating PD. Adding safinamide to l-dopa increases the time patients' symptoms are controlled so-called ON time, without increasing troublesome dyskinesia. Although safinamide has dopaminergic actions, recent data have suggested that the long-term effects of safinamide on dyskinesia are related to safinamide state- and use-dependent inhibition of sodium channels and stimulated glutamate release, rather than reduced dopaminergic stimulation. Safinamide's unique dual mechanism of action makes it a valuable treatment option for fluctuating PD patients.