Safinamide mesilate (Equfina® tablets 50 mg): Preclinical and clinical pharmacodynamics, efficacy, and safety

Abstract

Parkinson’s disease is a neurodegenerative disorder characterized by the degenerative loss of dopaminergic neurons in the substantia nigra. Dopamine deficiency is thought to disrupt motor control of the basal ganglia and cause characteristic motor symptoms in Parkinson’s disease such as bradykinesia, akinesia, and tremor. Therefore, dopamine replacement therapy is widely used in the clinical setting. Safinamide is a novel, selective, and reversible inhibitor of monoamine oxidase B expected to increase dopamine levels in the brain and improve the symptoms of Parkinson’s disease. In addition, safinamide shows non-dopaminergic actions such as sodium channel blockade and inhibition of glutamate release. Preclinical studies have demonstrated that safinamide ameliorates “wearing off” symptoms after administration in rat and monkey models with selectively destroyed dopaminergic neurons. In the monkeys, safinamide concurrently inhibited levodopa-induced dyskinesia. These findings suggest that safinamide not only increases the dopaminergic effect of levodopa, but also reduces levodopa-induced adverse events via its non-dopaminergic effects. In clinical trials of patients with Parkinson’s disease with the “wearing off” phenomenon, safinamide has been found to prolong the “on time” and improve motor function as assessed by Unified Parkinson’s Disease Rating Scale Part III. In Japan, safinamide was approved in September 2019 as a levodopa combination drug for Parkinson’s disease with “wearing off” phenomenon. Safinamide is therefore expected to be a new treatment option for patients with Parkinson’s disease.