1. Academic Validation
  2. Fenamates inhibit human sodium channel Nav1.7 and Nav1.8

Fenamates inhibit human sodium channel Nav1.7 and Nav1.8

  • Neurosci Lett. 2019 Mar 23;696:67-73. doi: 10.1016/j.neulet.2018.12.008.
Jian-Fang Sun 1 Yi-Jia Xu 2 Xiao-Hua Kong 3 Yang Su 4 Zhan-You Wang 5
Affiliations

Affiliations

  • 1 College of Life and Health Sciences, Northeastern University, Shenyang, 110169, PR China.
  • 2 School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, 110016, PR China. Electronic address: xyj0922@126.com.
  • 3 School of Life Sciences and Biopharmaceutical Science, Shenyang Pharmaceutical University, Shenyang, 110016, PR China.
  • 4 Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, PR China.
  • 5 College of Life and Health Sciences, Northeastern University, Shenyang, 110169, PR China. Electronic address: wangzy@cmu.edu.cn.
Abstract

Fenamates are N-substituted anthranilic acid derivatives, clinically used as nonsteroidal anti-inflammatory drugs (NSAIDs) in fever, pain and inflammation treatments. Previous studies have shown that they are also modulators of diverse ion channels, exhibiting either activation or inhibitory effects. However, the effects of fenamates on Sodium Channel subtypes are still unknown. In this study, fenamates, including mefenamic acid, flufenamic acid and tolfenamic acid, were examined by whole-cell patch clamp techniques on the sodium channels hNav1.7 and hNav1.8, which are closely associated with pain. The results showed that the mefenamic acid, flufenamic acid, and tolfenamic acid inhibited the peak currents of hNav1.7 and hNav1.8 in CHO cells stably expressing hNav1.7 and hNav1.8. However, much lighter inhibition effects of hNav1.8 were registered in the experimental system. Furthermore, the mefenamic acid, flufenamic acid and tolfenamic acid significantly affected the inactivation processes of hNav1.7 and hNav1.8 with I-V curves left-shifted to hyperpolarized direction. These data indicate that the inhibition effects of Nav1.7 and Nav1.8 by mefenamic acid, flufenamic acid and tolfenamic acid might contribute to their analgesic activity in addition to their inhibition of cyclooxygenase. These findings provide a basis for further studies in the discovery of other potential targets for NSAIDs.

Keywords

Fenamates; Nav1.7; Nav1.8; Pain.

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