Evaluation of edonerpic maleate as a CRMP2 inhibitor for pain relief

Aubin Moutal, Zhiming Shan, Victor G. Miranda, Liberty François-Moutal, Cynthia L. Madura, May Khanna, Rajesh Khanna

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We have previously reported that the microtubule-associated collapsin response mediator protein 2 (CRMP2) is necessary for the expression of chronic pain. CRMP2 achieves this control of nociceptive signaling by virtue of its ability to regulate voltage-gated calcium and sodium channels. To date, however, no drugs exist that target CRMP2. Recently, the small molecule edonerpic maleate (1 -{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate), a candidate therapeutic for Alzheimer’s disease was reported to be a novel CRMP2 binding compound with the potential to decrease its phosphorylation level in cortical tissues in vivo. Here we sought to determine the mechanism of action of edonerpic maleate and test its possible effect in a rodent model of chronic pain. We observed: (i) no binding between human CRMP2 and edonerpic maleate; (ii) edonerpic maleate had no effect on CRMP2 expression and phosphorylation in dorsal root ganglion (DRG) neurons; (iii) edonerpic maleate-decreased calcium but increased sodium current density in DRG neurons; and (iv) edonerpic maleate was ineffective in reversing post-surgical allodynia in male and female mice. Thus, while CRMP2 inhibiting compounds remain a viable strategy for developing new mechanism-based pain inhibitors, edonerpic maleate is an unlikely candidate.

Original languageEnglish (US)
Pages (from-to)498-504
Number of pages7
JournalChannels
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2019

Keywords

  • CRMP2
  • DRG sensory neuron
  • edonerpic maleate
  • ion channels
  • post-surgical pain

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

Fingerprint Dive into the research topics of 'Evaluation of edonerpic maleate as a CRMP2 inhibitor for pain relief'. Together they form a unique fingerprint.

Cite this