Retigabine is an anticonvulsant compound that activates low-threshold voltage-gated potassium channels [1]. Retigabine enhances potassium currents via destabilization of a closed conformation or stabilization of the open conformation of the potassium Kv7.2-7.3 channels[2]. Retigabine has been widely used to stabilize the resting membrane potential, reduce brain excitability, and enhance the current mediated by gamma-aminobutyric acid (GABA)[3].
In vitro, Retigabine treatment (10µM) for 48 hours prevented L-glutamate toxicity in PC12 cells, restored cell viability, and reduced the generation of reactive oxygen intermediates [4].
In vivo, Retigabine treatment via intraperitoneal injection at a dose of 15mg/kg every four hours for 12 hours significantly promoted the apoptosis of brain neurons in newborn rats[5].
References:
[1] Splinter M Y. Ezogabine (retigabine) and its role in the treatment of partial-onset seizures: a review[J]. Clinical therapeutics, 2012, 34(9): 1845-1856. e1.
[2] Czuczwar P, Wojtak A, Cioczek-Czuczwar A, et al. Retigabine: the newer potential antiepileptic drug[J]. Pharmacological Reports, 2010, 62(2): 211-219.
[3] Stafstrom C E, Grippon S, Kirkpatrick P. Ezogabine (retigabine)[J]. Nature Reviews Drug Discovery, 2011, 10(10): 729-730.
[4] Seyfried J, Evert B O, Rundfeldt C, et al. Flupirtine and retigabine prevent L-glutamate toxicity in rat pheochromocytoma PC 12 cells[J]. European journal of pharmacology, 2000, 400(2-3): 155-166.
[5] Brown L, Gutherz S, Kulick C, et al. Profile of retigabine‐induced neuronal apoptosis in the developing rat brain[J]. Epilepsia, 2016, 57(4): 660-670.