Rufinamide

Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple seizure types.¹ Rufinamide is an anticonvulsant.² It inhibits the activation of voltage-gated sodium channel 1.1 (Na_v1.1) when used at a concentration of 100 µM.³ 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).⁴ 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.⁵ It inhibits seizures induced by pentylenetetrazole (Item No. 18682) 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.^6,7 Formulations containing rufinamide have been used in the treatment of seizures associated with Lennox-Gastaut Syndrome (LGS).

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1. Al-Banji, M.H., Zahr, D., and Jan, M.M. Lennox-Gastaut syndrome. Management update. Neuroscience (Riyadh) 20(3), 207-212 (2015).

2. Wheless, J.W., and Vazquez, B. Rufinamide: A novel broad-spectrum antiepileptic drug. Epilepsy Curr. 10(1), 1-6 (2010).

3. Gilchrist, J.J., Dutton, S., Diaz-Bustamante, M., et al. Na_v1.1 modulation by a novel triazole compound attenuates epileptic seizures in rodents. ACS Chem. Biol. 9(5), 1204-1212 (2014).

4. Costa, G., Carta, F., Ambrosio, F.A., et al. A computer-assisted discovery of novel potential anti-obesity compounds as selective carbonic anhydrase VA inhibitors. Eur. J. Med. Chem. 181, 111565 (2019).

5. Gáll, Z., Orbán-Kis, K., and Szilágyi, T. Differential effects of sodium channel blockers on in vitro induced epileptiform activities. Arch. Pharm. Res. 40(1), 112-121 (2017).

6. White, H.S., Franklin, M.R., Kupferberg, H.J., et al. The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models. Epilepsia 49(7), 1213-1220 (2008).

7. Park, J.-A., and Lee, C.-H. Effect of Rufinamide on the kainic acid-induced excitotoxic neuronal death in the mouse hippocampus. Arch. Pharm. Res. 41(7), 776-783 (2018).