Safinamide Mesylate

DA-depleted C57BL mice

Safinamide is currently in a Phase II clinical trial in Parkinson's Disease.

20 mg/kg

sterile 0.9% sodium chloride solution

Safinamide is a highly selective MAO-B inhibitor in rat brain mitochondria, with an IC50 of 98 nM. safinamide inhibits MAO-B in human brain with an IC50 of 9 nM. Safinamide has high affinity for the Na+ channel-binding site II in rat cortical membranes, with an IC50 of 8 uM. Safinamide inhibits the fast Na+ currents in a concentration- and state-dependent manner in rat cortical neurons. Safinamide blocks N-Type Ca2+ currents in rat cortical neurons with IC50 23 uM. Safinamide inhibits glutamate release induced by depolarizing conditions in rat hippocampal synaptosomes with IC50 of 9 uM. Safinamide incubated 1 hour before veratridine reduces the neuron damage with an IC50 1.4 uM through blockade of opening voltage-dependent Na+ and Ca2+ channels in rat primary cortical neurons. [1] Safinamide binds to human MAO B with a Ki of 0.5 uM. Safinamide binds to human MAO B in an extended conformation occupying both flavin and entrance cavity. [2]

[3], Enzyme Activity Assay, The enzyme activities are assessed with a radioenzymatic assay using the selective substrates 14C-phenylethylamine (PEA) for MAO-B. The mitochondrial pellet (500 ug protein) is resuspended in 200 uL of 0.1 M phosphate buffer, pH 7.40, and is added to 50 uL of the solution of safinamide or of buffer and incubated for 30 min at 37 C (preincubation). Then the substrate in 50 uL of 0.5 uM 14CPEA is added and the assay mixture is incubated at 37 C for 10 min. The reaction is stopped by adding 0.2 mL of perchloric acid. After centrifugation, the acidic radioactive metabolites are extracted with 3 mL of toluene and the radioactivity of the organic phase is measured by liquid scintillation spectrometry at 90% efficiency. The enzymatic activity is expressed as nanomoles of substrate transformed per milligram of protein per minute (nmol mg-1 min-1). Safinamide inhibition curves are obtained from five to eight different concentrations (10-10-10-5 M), each in duplicate, and the IC50 is determined using nonlinear regression analysis.

Safinamide Mesylate (FCE28073) Chemical Structure

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO