Safinamide mesylate (EMD 1195686 mesylate) , a mesylate salt of Safinamide, can reversibly and specifically inhibit MAO-B (IC50: 98 nM), has 5918-fold selectivity against MAO-A.

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

Safinamide (p.o.) dose-dependently inhibits mouse brain MAO-B (IC50: 0.6 mg/kg), and MAO-B activity recovers quickly, starting from 8 hours. Safinamide markedly inhibits cell body degeneration in the substantia nigra pars compacta. Safinamide intraperitoneally administered 15 minutes before kainic acid protects against hippocampal neuron loss, starting at 10 mg/kg showing neuroprotective properties. Safinamide (100 mg/kg, i.p.) shows a relevant neuro rescuing effect on hippocampal neurons when given 3 hours after ischemia. Safinamide has a high oral bioavailability (80-92%), is rapidly absorbed in plasma after reaching the peak within 0.5-2 hours declines, with a terminal half-life of about 3, 7, and 13 hours in mice, rats, and monkeys, respectively.

Animal Models: DA-depleted C57BL miceFormulation: sterile 0.9% sodium chloride solutionDosages: 20 mg/kgAdministration: Inject intraperitoneally in a single dose