Rufinamide-15N-d2

Rufinamide-¹⁵N-d₂ is intended for use as an internal standard for the quantification of rufinamide by GC- or LC-MS. Rufinamide is an anticonvulsant.¹ It inhibits the activation of voltage-gated sodium channel 1.1 (Na_v1.1) when used at a concentration of 100 µM.² Rufinamide inhibits Na_v1.1, but not Na_v1.2, Na_v1.3, and Na_v1.6, opening and increases the action potential threshold in primary rat hippocampal neurons. It is an inhibitor of carbonic anhydrase VA (CAVA; K_i = 343.8 nM) that is selective for CAVA over CAI and CAII (K_is = >10,000 nM for both).³ Rufinamide (100 µM) prolongs the preictal phase and reduces seizure-like event frequency in an in vitro model of epileptiform activity in rat hippocampal slices.⁴ It inhibits seizures induced by pentylenetetrazole in a mouse model of epilepsy (ED₅₀ = 54 mg/kg, i.p.) and reduces kainic acid-induced neuronal cell death in the mouse hippocampal CA3 region when used at doses of 25, 50, and 100 mg/kg.^5,6 Formulations containing rufinamide have been used in the treatment of seizures associated with Lennox-Gastaut Syndrome (LGS).

1.Wheless, J.W., and Vazquez, B.Rufinamide: A novel broad-spectrum antiepileptic drugEpilepsy Curr.10(1)1-6(2010) 2.Gilchrist, J.J., Dutton, S., Diaz-Bustamante, M., et al.Nav1.1 modulation by a novel triazole compound attenuates epileptic seizures in rodentsACS Chem. Biol.9(5)1204-1212(2014) 3.Costa, G., Carta, F., Ambrosio, F.A., et al.A computer-assisted discovery of novel potential anti-obesity compounds as selective carbonic anhydrase VA inhibitorsEur. J. Med. Chem.181111565(2019) 4.GÁll, Z., OrbÁn-Kis, K., and SzilÁgyi, T.Differential effects of sodium channel blockers on in vitro induced epileptiform activitiesArch. Pharm. Res.40(1)112-121(2017) 5.White, H.S., Franklin, M.R., Kupferberg, H.J., et al.The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure modelsEpilepsia49(7)1213-1220(2008) 6.Park, J.-A., and Lee, C.-H.Effect of Rufinamide on the kainic acid-induced excitotoxic neuronal death in the mouse hippocampusArch. Pharm. Res.41(7)776-783(2018)