PubMed 25987375

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , Kv7.2

Title: Discovery of a novel Kv7 channel opener as a treatment for epilepsy.

Authors: Jennifer E Davoren, Michelle M Claffey, Sheri L Snow, Matthew R Reese, Gaurav Arora, Christopher R Butler, Brian P Boscoe, Lois Chenard, Shari L DeNinno, Susan E Drozda, Allen J Duplantier, Ludivine Moine, Bruce N Rogers, SuoBao Rong, Katherine Schuyten, Ann S Wright, Lei Zhang, Kevin A Serpa, Mark L Weber, Polina Stolyar, Tammy L Whisman, Karen Baker, Karen Tse, Alan J Clark, Haojing Rong, Robert J Mather, John A Lowe

Journal, date & volume: Bioorg. Med. Chem. Lett., 2015 Nov 1 , 25, 4941-4

PubMed link:

Facilitating activation, or delaying inactivation, of the native Kv7 channel reduces neuronal excitability, which may be beneficial in controlling spontaneous electrical activity during epileptic seizures. In an effort to identify a compound with such properties, the structure-activity relationship (SAR) and in vitro ADME for a series of heterocyclic Kv7.2-7.5 channel openers was explored. PF-05020182 (2) demonstrated suitable properties for further testing in vivo where it dose-dependently decreased the number of animals exhibiting full tonic extension convulsions in response to corneal stimulation in the maximal electroshock (MES) assay. In addition, PF-05020182 (2) significantly inhibited convulsions in the MES assay at doses tested, consistent with in vitro activity measure. The physiochemical properties, in vitro and in vivo activities of PF-05020182 (2) support further development as an adjunctive treatment of refractory epilepsy.