Discovery of Nonpungent Transient Receptor Potential Vanilloid 1 (TRPV1) Agonist as Strong Topical Analgesic.
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Ann J, Kim HS, Thorat SA, Kim H, Ha HJ, Choi K, Kim YH, Kim M, Hwang SW, Pearce LV, Esch TE, Turcios NA, Blumberg PM, Lee J
Discovery of Nonpungent Transient Receptor Potential Vanilloid 1 (TRPV1) Agonist as Strong Topical Analgesic.
J Med Chem. 2020 Jan 9;63(1):418-424. doi: 10.1021/acs.jmedchem.9b01046. Epub 2019 Nov 26.
- PubMed ID
- 31702924 [ View in PubMed]
- Abstract
Paradoxically, some TRPV1 agonists are, at the organismal level, both nonpungent and clinically useful as topical analgesics. Here, we describe the scaled-up synthesis and characterization in mouse models of a novel, nonpungent vanilloid. Potent analgesic activity was observed in models of neuropathic pain, and the compound blocked capsaicin induced allodynia, showing dermal accumulation with little transdermal absorption. Finally, it displayed much weaker systemic toxicity compared to capsaicin and was negative in assays of genotoxicity.