Enhancing inactivation rather than reducing activation of Nav1.7 channels by a clinically effective analgesic CNV1014802.

ABSTRACT: The Nav1.7 channel represents a promising target for pain relief. In the recent decades, a number of Nav1.7 channel inhibitors have been developed. According to the effects on channel kinetics, these inhibitors could be divided into two major classes: reducing activation or enhancing inactivation. To date, however, only several inhibitors have moved forward into phase 2 clinical trials and most of them display a less than ideal analgesic efficacy, thus intensifying the controversy regarding if an ideal candidate should preferentially affect the activation or inactivation state. In the present study, we investigated the action mechanisms of a recently clinically confirmed inhibitor CNV1014802 using both electrophysiology and site-directed mutagenesis. We found that CNV1014802 inhibited Nav1

SUBMITTER: Zheng YM 

PROVIDER: S-EPMC5888685 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature