Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8

Title: Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain.

Authors: Mark D Andrews, Kerry Af Forselles, Kevin Beaumont, Sébastien R G Galan, Paul A Glossop, Mathilde Grenie, Alan Jessiman, Amy S Kenyon, Graham Lunn, Graham Maw, Robert M Owen, David C Pryde, Dannielle Roberts, Thien Duc Tran

Journal, date & volume: ACS Med Chem Lett, 2015 Apr 9 , 6, 419-24

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25893043

Abstract
The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 °C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.