MEDI 317 |
| Vanilloid receptor 1 (TRPV1) is a ligand gated non-selective cation channel and recognized as a polymodal nociceptor that integrates multiple pain stimuli. A major distribution of TRPV1 is in the sensory fibers, which are bipolar neurons having somata in sensory ganglia. The peripheral fibers of these neurons innervate the skin, the mucosal membranes, and almost all internal organs. A body of studies using TRPV1 agonists and antagonists have suggested that TRPV1 positive nerves are thought to participate in a variety of physiological responses, including nociception. Based on both the tissue distribution and the roles of TRPV1, TRPV1 antagonists would have good therapeutic potentials for pain relief. We began with a high through put screening of the Pfizer sample bank and identified several lead compounds. The modification of these compounds led us to the identification of potent, selective and orally active TRPV1 antagonists. This presentation will cover the identification and characterization of unique peripherally restricted TRPV1 antagonists suitable for clinical development. |
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Antagonists of TRP Channels and Vanilloid Receptors
1:30 PM-4:55 PM, Wednesday, 13 September 2006 Moscone Center -- Room 102, Oral
Division of Medicinal Chemistry |