Safinamide  (Synonyms: FCE 26743; EMD 1195686)

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].

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

302.34

Solid

C₁₇H₁₉FN₂O₂

133865-89-1

O=C([C@@H](NCC1=CC=C(OCC2=CC(F)=CC=C2)C=C1)C)N

Room temperature in continental US; may vary elsewhere.

• [1]. Leonetti F, et al. Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase. J Med Chem, 2007, 50(20), 4909-4916.  [Content Brief]

  [2]. C Caccia, et al.Safinamide: from molecular targets to a new anti-Parkinson drug. Neurology. 2006 Oct 10;67(7 Suppl 2):S18-23.  [Content Brief]

  [3]. Michele Morari, et al. Safinamide Differentially Modulates In Vivo Glutamate and GABA Release in the Rat Hippocampus and Basal Ganglia.J Pharmacol Exp Ther. 2018 Feb;364(2):198-206.  [Content Brief]