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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). |
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