Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Na(v)1.8 sodium channel with efficacy in a model of neuropathic pain.

@article{Scanio2010DiscoveryAB,
  title={Discovery and biological evaluation of potent, selective, orally bioavailable, pyrazine-based blockers of the Na(v)1.8 sodium channel with efficacy in a model of neuropathic pain.},
  author={Marc J C Scanio and Lei Shi and Irene Drizin and Robert J. Gregg and Robert N. Atkinson and James B. Thomas and Matthew S. Johnson and Mark L. Chapman and Dong Liu and Michael J Krambis and Yi Liu and Char-Chang Shieh and Xu-Feng Zhang and Gricelda H Simler and Shailen K. Joshi and Prisca Honore and Kennan C. Marsh and Alison M. Knox and Stephen Werness and Brett Antonio and Douglas S. Krafte and Michael F. Jarvis and Connie R. Faltynek and Brian E. Marron and Michael Kort},
  journal={Bioorganic & medicinal chemistry},
  year={2010},
  volume={18 22},
  pages={7816-25}
}
Na(v)1.8 (also known as PN3) is a tetrodotoxin-resistant (TTx-r) voltage-gated sodium channel (VGSC) that is highly expressed on small diameter sensory neurons. It has been implicated in the pathophysiology of inflammatory and neuropathic pain, and we envisioned that selective blockade of Na(v)1.8 would be analgesic, while reducing adverse events typically… CONTINUE READING