Safinamide

Safinamide is a potent, selective, and reversible monoamine oxidase B (MAO-B) inhibitor (IC₅₀=0.098 μM) over MAO-A (IC₅₀=580 μM)^[1]. Safinamide 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 has neuroprotective and neurorescuing effects and can be used for the study of parkinson disease, ischemia stroke etc.al^[2][3]. IC50 & Target:IC50: 98 nM (MAO-B)^[1] In Vitro: Safinamide (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 with a lower IC₅₀?value (8?μM) in rat cortical neurons^[1].
In Vivo: Safinamide (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 (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 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 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].