product name Safinamide
Description: Safinamide (EMD 1195686; FCE 26743) selectively and reversibly inhibits MAO-B with IC50 of 98 nM, exhibits 5918-fold selectivity against MAO-A. In addition, Safinamide is voltage-dependent sodium and calcium channel blocker. It appears to bind to the batrachotoxin-sensitive site 2 of the voltage-sensitive sodium channels. Safinamide blocks N and L-type calcium channels and inhibits glutamate and aspartate release from synaptic terminals.
References: Neurology. 2006 Oct 10;67(7 Suppl 2):S18-23; J Med Chem. 2007 Nov 15;50(23):5848-52.
302.34
Formula
C17H19FN2O2
CAS No.
133865-89-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 10 mM
Water:
Ethanol:
Solubility (In vivo)
Synonyms
PNU-151774E,FCE28073
other peoduct :
| In Vitro |
In vitro activity: 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 μM. 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 of 23 μM. Safinamide inhibits glutamate release induced by depolarizing conditions in rat hippocampal synaptosomes with IC50 of 9 μM. Safinamide incubated 1 hour before veratridine reduces the neuron damage with an IC50 1.4 μM through blockade of opening voltage-dependent Na+ and Ca2+ channels in rat primary cortical neurons. Safinamide binds to human MAO B with a Ki of 0.5 μM. Safinamide binds to human MAO B in an extended conformation occupying both flavin and entrance cavity. Kinase Assay: Safinamide (EMD 1195686; FCE 26743) selectively and reversibly inhibits MAO-B with IC50 of 98 nM, exhibits 5918-fold selectivity against MAO-A. Cell Assay: |
|---|---|
| In Vivo | Safinamide orally administrated dose-dependently inhibits mouse brain MAO-B with IC50 of 0.6 mg/kg, and MAO-B activity recovers quickly, starting from 8 hours. Safinamide significantly 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 intraperitoneally administrated at dose of 100 mg/kg shows a relevant neurorescuing 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 model | DA-depleted C57BL mice |
| Formulation & Dosage | Dissolved in 0.9% sodium chloride solution; 20 mg/kg; i.p. injection |
| References | Neurology. 2006 Oct 10;67(7 Suppl 2):S18-23; J Med Chem. 2007 Nov 15;50(23):5848-52. |
