{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T22:40:52Z","timestamp":1772923252335,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,2,17]],"date-time":"2009-02-17T00:00:00Z","timestamp":1234828800000},"content-version":"vor","delay-in-days":1630,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2004,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Openers of ATP\u2010sensitive K<jats:sup>+<\/jats:sup> channels are of interest in several therapeutic indications including overactive bladder and other lower urinary tract disorders. This study reports on the <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> characterization of a structurally novel naphthylamide <jats:italic>N<\/jats:italic>\u2010[2\u2010(2,2,2\u2010trifluoro\u20101\u2010hydroxy\u20101\u2010trifluoromethyl\u2010ethyl)\u2010naphthalen\u20101\u2010yl]\u2010acetamide (A\u2010151892), as an opener of the ATP\u2010sensitive potassium channels.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A\u2010151892 was found to be a potent and efficacious potassium channel opener (KCO) as assessed by glibenclamide\u2010sensitive whole\u2010cell current and fluorescence\u2010based membrane potential responses (\u2212log EC<jats:sub>50<\/jats:sub>=7.63) in guinea\u2010pig bladder smooth muscle cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Evidence for direct interaction with KCO binding sites was derived from displacement of binding of the 1,4\u2010dihydropyridine opener [<jats:sup>125<\/jats:sup>I]A\u2010312110. A\u2010151892 displaced [<jats:sup>125<\/jats:sup>I]A\u2010312110 binding to bladder membranes with a \u2212log Ki value of 7.45, but lacked affinity against over 70 neurotransmitter receptor and ion channel binding sites.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In pig bladder strips, A\u2010151892 suppressed phasic, carbachol\u2010evoked and electrical field stimulus\u2010evoked contractility in a glibenclamide\u2010reversible manner with \u2212log IC<jats:sub>50<\/jats:sub> values of 8.07, 7.33 and 7.02 respectively, comparable to that of the potencies of the prototypical cyanoguanidine KCO, P1075. The potencies to suppress contractions in thoracic aorta (\u2212log IC<jats:sub>50<\/jats:sub>=7.81) and portal vein (\u2212log IC<jats:sub>50<\/jats:sub>=7.98) were not substantially different from those observed for suppression of phasic contractility of the bladder smooth muscle.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p> <jats:italic>In vivo<\/jats:italic>, A\u2010151892 was found to potently suppress unstable bladder contractions in obstructed models of unstable contractions in both pigs and rats with pED<jats:sub>35%<\/jats:sub> values of 8.05 and 7.43, respectively.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results demonstrate that naphthylamide analogs exemplified by A\u2010151892 are novel K<jats:sub>ATP<\/jats:sub> channel openers and may serve as chemotypes to exploit additional analogs with potential for the treatment of overactive bladder and lower urinary tract symptoms.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p> <jats:italic>British Journal of Pharmacology<\/jats:italic> (2004) <jats:bold>143<\/jats:bold>, 81\u201390. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705908\">10.1038\/sj.bjp.0705908<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705908","type":"journal-article","created":{"date-parts":[[2004,9,2]],"date-time":"2004-09-02T20:31:48Z","timestamp":1094157108000},"page":"81-90","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<i>In vitro<\/i> and <i>in vivo<\/i> characterization of a novel naphthylamide ATP\u2010sensitive K<sup>+<\/sup> channel opener, A\u2010151892"],"prefix":"10.1111","volume":"143","author":[{"given":"Murali","family":"Gopalakrishnan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven 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