{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T11:55:04Z","timestamp":1781870104581,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,1,4]],"date-time":"2005-01-04T00:00:00Z","timestamp":1104796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2005,4]]},"abstract":"<jats:p><jats:bold>Abstract\u2002<\/jats:bold> Therapeutic use of 5\u2010hydroxytryptamine 3 (5\u2010HT<jats:sub>3<\/jats:sub>) receptor antagonists for diarrhoea\u2010predominant irritable bowel syndrome may be accompanied by constipation. We hypothesized that ME3412, 5\u2010chloro\u20102\u2010(1,4\u2010diazacycloheptan\u20101\u2010yl)\u20107\u2010methylbenzoxazole, a novel partial agonist of the 5\u2010HT<jats:sub>3<\/jats:sub> receptor, would minimize constipation without reducing antidiarrhoeal activity. Receptor binding studies showed that ME3412 is highly selective for the human 5\u2010HT<jats:sub>3<\/jats:sub> receptor (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>\u2003=\u20031.51\u2003nmol\u2003L<jats:sup>\u22121<\/jats:sup>). A 5\u2010HT<jats:sub>3<\/jats:sub> receptor agonist, 2\u2010methyl\u20105\u2010HT, caused contractile response in the isolated guinea\u2010pig ileum and accelerated secretion in the guinea\u2010pig colonic mucosal preparation. ME3412 and 5\u2010HT<jats:sub>3<\/jats:sub> receptor antagonist, alosetron, antagonized the 2\u2010methyl\u20105\u2010HT\u2010induced responses with similar potency in insurmountable and surmountable manner, respectively. ME3412 caused weak agonism in isolated ileum strips and also in the colonic mucosa with intrinsic activity of 0.09 and 0.59, respectively. In conscious dogs, alosetron (3\u2003<jats:italic>\u03bc<\/jats:italic>g\u2003kg<jats:sup>\u22121<\/jats:sup> i.v.) suppressed the migrating motor complex (MMC), whereas a relatively high dose (300\u2003<jats:italic>\u03bc<\/jats:italic>g\u2003kg<jats:sup>\u22121<\/jats:sup>) of ME3412 was required for inhibition of MMC. ME3412 and alosetron suppressed 5\u2010HT induced\u2010diarrhoea in mice. In contrast, ME3412 did not significantly affect colonic propulsion compared with alosetron. These results imply that the partial agonist may relieve diarrhoea with low risk of inducing constipation.<\/jats:p>","DOI":"10.1111\/j.1365-2982.2004.00622.x","type":"journal-article","created":{"date-parts":[[2005,3,19]],"date-time":"2005-03-19T12:41:00Z","timestamp":1111236060000},"page":"290-301","source":"Crossref","is-referenced-by-count":9,"title":["Comparison between partial agonist (ME3412) and antagonist (alosetron) of 5\u2010hydroxytryptamine 3 receptor on gastrointestinal function"],"prefix":"10.1111","volume":"17","author":[{"given":"K.","family":"Kawano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Niisato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Shiokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Shishikura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,1,4]]},"reference":[{"key":"e_1_2_20_2_2","volume-title":"The Functional Gasrointestinal Disorders","author":"Drossman D","year":"2000"},{"key":"e_1_2_20_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a116483"},{"key":"e_1_2_20_4_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-116-12-1009"},{"key":"e_1_2_20_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00042737-199704000-00002"},{"key":"e_1_2_20_6_2","first-page":"425","article-title":"Pharmacology of indole alkylamines","volume":"6","author":"Erspamer V.","year":"1954","journal-title":"Pharmacol Rev"},{"key":"e_1_2_20_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1999.00002.x-i2"},{"key":"e_1_2_20_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.42.1.42"},{"key":"e_1_2_20_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1550-8528.1995.tb00503.x"},{"key":"e_1_2_20_10_2","first-page":"272","article-title":"Effects of 5\u2010hydroxytryptamine 3 receptor antagonists on gastrointestinal motor activity in conscious dogs","volume":"256","author":"Yoshida N","year":"1991","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_20_11_2","first-page":"297","article-title":"Role of the serotonin3 receptor in stress\u2010induced defecation","volume":"261","author":"Miyata K","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_20_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90395-X"},{"key":"e_1_2_20_13_2","first-page":"G68","article-title":"5\u2010HT\u2010induced colonic contractions: enteric locus of action and receptor subtypes","volume":"273","author":"Graf S","year":"1997","journal-title":"Am J Physiol"},{"key":"e_1_2_20_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02033-X"},{"key":"e_1_2_20_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0950-3528(94)90006-X"},{"key":"e_1_2_20_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042-7158.1994.tb03879.x"},{"key":"e_1_2_20_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01425-X"},{"key":"e_1_2_20_18_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.20.752"},{"key":"e_1_2_20_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm9801004"},{"key":"e_1_2_20_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12257.x"},{"key":"e_1_2_20_21_2","first-page":"G833","article-title":"Neural 5\u2010hydroxytryptamine receptors regulate chloride secretion in guinea\u2010pig distal colon","volume":"261","author":"Cooke HJ","year":"1991","journal-title":"Am J Physiol"},{"key":"e_1_2_20_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02776795"},{"key":"e_1_2_20_23_2","doi-asserted-by":"publisher","DOI":"10.1540\/jsmr.29.47"},{"key":"e_1_2_20_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(73)90196-2"},{"key":"e_1_2_20_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1990.tb12088.x"},{"key":"e_1_2_20_26_2","first-page":"299","article-title":"Cumulative dose\u2013response curves II. 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