{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:18:01Z","timestamp":1785734281285,"version":"3.56.0"},"reference-count":47,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>\n                    The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC\n                    <jats:sub>90<\/jats:sub>\n                    of 300\u2009nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0.2), and orally bioavailable small molecule TRPA1 antagonist. AMG0902 reduced mechanically evoked C-fiber action potential firing in a skin-nerve preparation from mice previously injected with complete Freund\u2019s adjuvant, supporting the role of TRPA1 in inflammatory mechanosensation. In\u00a0vivo target coverage of TRPA1 by AMG0902 was demonstrated by the prevention of AITC-induced flinching\/licking in rats. However, oral administration of AMG0902 to rats resulted in little to no efficacy in models of inflammatory, mechanically evoked hypersensitivity; and no efficacy was observed in a neuropathic pain model. Unbound plasma concentrations achieved in pain models were about 4-fold higher than the IC\n                    <jats:sub>90<\/jats:sub>\n                    concentration in the AITC target coverage model, suggesting that either greater target coverage is required for efficacy in the pain models studied or TRPA1 may not contribute significantly to the underlying mechanisms.\n                  <\/jats:p>","DOI":"10.1177\/1744806916677761","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T23:32:12Z","timestamp":1480462332000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":30,"title":["Selective antagonism of TRPA1 produces limited efficacy in models of inflammatory- and neuropathic-induced mechanical hypersensitivity in rats"],"prefix":"10.1177","volume":"12","author":[{"given":"Sonya G","family":"Lehto","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Amgen Inc, Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy D","family":"Weyer","sequence":"additional","affiliation":[{"name":"School of Physical Therapy, Pacific University, Hillsboro, OR, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth D","family":"Youngblood","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Amgen Inc, Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maosheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Amgen Inc, Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyuan","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Amgen Inc, Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiya","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Amgen Inc, Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohannes","family":"Teffera","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics and Drug Metabolism, Amgen Inc, Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Amgen Inc, Thousand Oaks, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl L","family":"Stucky","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Schenkel","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry, Amgen Inc, Cambridge, MA, 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