Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent

Bioorg Med Chem. 2012 Sep 1;20(17):5269-76. doi: 10.1016/j.bmc.2012.06.042. Epub 2012 Jul 3.

Abstract

Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater functional blockade with greatly reduced toxicity. Compound 2 reduced mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo in sensory neuron axons with two-photon microscopy. These results suggest a promising strategy for developing novel sodium channel inhibitors with imaging capabilities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Design
  • Female
  • Fluorescence*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Neuralgia / drug therapy*
  • Phenytoin / chemical synthesis
  • Phenytoin / chemistry
  • Phenytoin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channel Blockers / chemical synthesis
  • Sodium Channel Blockers / chemistry
  • Sodium Channel Blockers / pharmacology*
  • Structure-Activity Relationship

Substances

  • Fluorescent Dyes
  • Sodium Channel Blockers
  • Phenytoin