PT  - JOURNAL ARTICLE
AU  - Xiao-fei Zhuang
AU  - Yu-xue Liu
AU  - Zhi-hong Yang
AU  - Qin Gao
AU  - Lei Wang
AU  - Chuanxia Ju
AU  - KeWei Wang
TI  - Attenuation of Epileptogenesis and Cognitive Deficits by a Selective and Potent Kv7 Channel Opener in Rodent Models of Seizures
AID  - 10.1124/jpet.122.001328
DP  - 2023 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 315--325
VI  - 384
IP  - 2
4099  - http://jpet.aspetjournals.org/content/384/2/315.short
4100  - http://jpet.aspetjournals.org/content/384/2/315.full
SO  - J Pharmacol Exp Ther2023 Feb 01; 384
AB  - Targeting neuronal Kv7 channels by pharmacological activation has been proven to be an attractive therapeutic strategy for epilepsy. Here, we show that activation of Kv7 channels by an opener SCR2682 dose-dependently reduces seizure activity and severity in rodent models of epilepsy induced by a GABAa receptor antagonist pentylenetetrazole (PTZ), maximal electroshock, and a glutamate receptor agonist kainic acid (KA). Electroencephalographic recordings of rat cerebral cortex confirm that SCR2682 also decreases epileptiform discharges in KA-induced seizures. Nissl and neuronal nuclei staining further demonstrates that SCR2682 also protects neurons from injury induced by KA. In Morris water maze navigation and Y-maze tests, SCR2682 improves PTZ- and KA-induced cognitive impairment. Taken together, our findings demonstrate that pharmacological activation of Kv7 by novel opener SCR2682 may hold promise for therapy of epilepsy with cognitive impairment.SIGNIFICANCE STATEMENT A neuronal Kv7 channel opener SCR2682 attenuates epileptogenesis and seizure-induced cognitive impairment in rodent models of seizures, thus possessing a developmental potential for effective therapy of epilepsy with cognitive impairment.