Safinamide (mesylate)

Safinamide (FCE 26743; EMD 1195686) mesylate is a potent, selective, and reversible monoamine oxidase B (MAO-B) inhibitor (IC₅₀=0.098 μM) over MAO-A (IC₅₀=580 nM)^[1]. Safinamide mesylate also blocks sodium channels and modulates glutamate (Glu) release, showing a greater affinity at depolarized (IC₅₀=8 μM) than at resting (IC₅₀=262 μM) potentials. Safinamide mesylate has neuroprotective and neurorescuing effects and can be used for the study of parkinson disease, ischemia stroke et.al^[2][3]. In Vitro:Safinamide mesylate (1-300 μM) reduces the amplitude of the peak sodium currents in a concentration-dependent manner. When currents are stimulated to a V_test of +10 mV from a V_h of -110 mV, the IC₅₀ value was 262 μM. When the holding potential is depolarized to -53 mV, the inhibitory effect of Safinamide mesylate with a lower IC₅₀ value (8 μM) in rat cortical neurons^[1].
In Vivo:Safinamide mesylate (intraperitoneal injection; 90 mg/kg; once daily; 14 days) treatment prior to MCAO significantly ameliorates MCAO-caused cerebral infarction volume, neurological deficit, disruption of the brain-blood barrier (BBB), and impairs expression of tight junction protein occludin and ZO-1 in mice^[3].
Safinamide mesylate (intraperitoneal injection; 5 mg/kg, 15 mg/kg and 30 mg/kg) dose dependently inhibits the veratridine-induced GABA release and Glu release in vivo. At the dose 30 mg/kg, Safinamide mesylate prevents the effect of veratridine both on Glu (treatment F1,8=1.31; time×treatment interaction F8,64=2.4) and GABA (treatment F1,8=4.04; time F8,64=3.76, time×treatment interaction F8,64=2.83) release.
Safinamide mesylate causes a slight, albeit not significant, reduction of veratridine-stimulated Glu release at 0.5 mg/kg and full inhibition at 5 and 15 mg/kg in rat^[3].