{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T21:43:39Z","timestamp":1789249419704,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T00:00:00Z","timestamp":1582675200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004820","name":"Mochida Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recently, we identified a novel fatty acid amide hydrolase (FAAH) inhibitor, PKM\u2010833 [(<jats:italic>R<\/jats:italic>)\u2010<jats:italic>N<\/jats:italic>\u2010(pyridazin\u20103\u2010yl)\u20104\u2010(7\u2010(trifluoromethyl)chroman\u20104\u2010yl)piperazine\u20101\u2010carboxamide]. The aim of the present study is to characterize the pharmacological profile of PKM\u2010833 in vitro and in vivo. PKM\u2010833 showed potent inhibitory activities against human and rat FAAH with IC<jats:sub>50<\/jats:sub> values of 8.8 and 10\u00a0nmol\/L, respectively, 200\u2010fold more selectivity against other 137 molecular targets, and irreversible mode of action. In pharmacokinetic and pharmacodynamic studies, PKM\u2010833 showed excellent brain penetration and good oral bioavailability, and elevated anandamide (AEA) concentrations in the rat brain. These data indicate that PKM\u2010833 is a potent, selective, orally active, and brain\u2010penetrable FAAH inhibitor. In behavioral studies using rat models, PKM\u2010833 significantly attenuated formalin\u2010induced pain responses (3\u00a0mg\/kg) and improved mechanical allodynia in complete freund's adjuvant (CFA)\u2010induced inflammatory pain (0.3\u20103\u00a0mg\/kg). On the other hand, PKM\u2010833 did not show the analgesic effects against mechanical allodynia in chronic constriction injury (CCI)\u2010induced neuropathic pain up to 30\u00a0mg\/kg. Regarding side effects, PKM\u2010833 had no significant effects on catalepsy and motor coordination up to 30\u00a0mg\/kg. These results indicate that PKM\u2010833 is a useful pharmacological agent that can be used to investigate the role of FAAH and may have therapeutic potential for the treatment of inflammatory pain without undesirable side effects.<\/jats:p>","DOI":"10.1002\/prp2.569","type":"journal-article","created":{"date-parts":[[2020,2,26]],"date-time":"2020-02-26T14:06:18Z","timestamp":1582725978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological characterization of a novel, potent, selective, and orally active fatty acid amide hydrolase inhibitor, PKM\u2010833 [(<i>R<\/i>)\u2010<i>N<\/i>\u2010(pyridazin\u20103\u2010yl)\u20104\u2010(7\u2010(trifluoromethyl)chroman\u20104\u2010yl)piperazine\u20101\u2010carboxamide] in rats: Potential for the treatment of inflammatory pain"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9640-2271","authenticated-orcid":false,"given":"Toshiya","family":"Endo","sequence":"first","affiliation":[{"name":"Biology Laboratory Discovery Research Mochida Pharmaceutical Co., Ltd. Gotemba Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Biology Laboratory Discovery Research Mochida Pharmaceutical Co., Ltd. Gotemba Shizuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8915-3825","authenticated-orcid":false,"given":"Shunsuke","family":"Maehara","sequence":"additional","affiliation":[{"name":"Biology Laboratory Discovery Research Mochida Pharmaceutical Co., Ltd. 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