Safinamide-d4 is intended for use as an internal standard for the quantification of safinamide by GC- or LC-MS. Safinamide is an inhibitor of monoamine oxidase B (MAO-B; IC50 = ~0.1 μM).1 It is selective for MAO-B over MAO-A (IC50 = >10 μM). It also inhibits radioligand binding to sodium channel binding site 2, sigma-1, and sigma-2 receptors in rat brain membranes (IC50s = 8.2, 0.019, and 1.59 μM, respectively).2 Safinamide inhibits high voltage-activated calcium currents and depolarization-induced tetrodotoxin-sensitive fast sodium currents in rat hippocampal neurons in a concentration-dependent manner. It inhibits veratrine-induced glutamate release in rat hippocampal slices (IC50 = 56 μM). Safinamide inhibits maximal electroshock-induced tonic extension seizures in mice and rats (ED50s = 8 and 11.8 mg/kg, p.o.) as well as maximal seizures induced by bicuculline , picrotoxin , 3-mercaptopropionic acid, and strychnine in mice (ED50s = 26.9, 60.6, 21.5, and 104.1 mg/kg, p.o., respectively).3 Formulations containing safinamide have been used as adjunctive treatments to levodopa and carbidopa in the treatment of "off" episodes associated with Parkinson's disease.
References
1. Strolin Benedetti, M.S., Marrari, P., Colombo, M., et al. The anticonvulsant FCE 26743 is a selective and short-acting MAO-B inhibitor devoid of inducing properties towards cytochrome P450-dependent testosterone hydroxylation in mice and rats. J. Pharm. Pharmacol. 46(10), 814-819 (1994).
2. Salvati, P., Maj, R., Caccia, C., et al. Biochemical and electrophysiological studies on the mechanism of action of PNU-151774E, a novel antiepileptic compound. J. Pharmacol. Exp. Ther. 288(3), 1151-1159 (1999).
3. Fariello, R.G., McArthur, R.A., Bonsignori, A., et al. Preclinical evaluation of PNU-151774E as a novel anticonvulsant. J. Pharmacol. Exp. Ther. 285(2), 397-403 (1998).