{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T21:55:33Z","timestamp":1778018133238,"version":"3.51.4"},"reference-count":41,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,5,21]],"date-time":"2013-05-21T00:00:00Z","timestamp":1369094400000},"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":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Constipation\u2010predominant irritable bowel syndrome (<jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010C) is a common functional gastrointestinal (<jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content>) disorder with abdominal pain and decreased motility. Current treatments of <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010C are insufficient. The aim of this study was to evaluate the potential application of taranabant, a cannabinoid type 1 (<jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1) inverse agonist using mouse models mimicking the symptoms of <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010C.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Changes in intestinal contractile activity were studied in vitro, using isolated mouse ileum and colon and intracellular recordings. <jats:italic>In vivo<\/jats:italic>, whole gastrointestinal transit (<jats:styled-content style=\"fixed-case\">WGT<\/jats:styled-content>) and fecal pellet output (<jats:styled-content style=\"fixed-case\">FPO<\/jats:styled-content>) were measured under standard conditions and with pharmacologically delayed <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> transit. The antinociceptive effect was evaluated in mustard oil\u2010 and acetic acid\u2010induced models of visceral pain. Forced swimming and tail suspension tests were performed and locomotor activity was measured to evaluate potential central side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In vitro, taranabant (10<jats:sup>\u221210<\/jats:sup>\u201310<jats:sup>\u22127<\/jats:sup>\u00a0mol\u00a0L<jats:sup>\u22121<\/jats:sup>) increased contractile responses in mouse ileum and blocked the effect of the <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content> agonist <jats:styled-content style=\"fixed-case\">WIN<\/jats:styled-content> 55,212\u20102. Taranabant had no effect on the amplitude of electrical field stimulation (<jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>)\u2010evoked junction potentials. In vivo, taranabant (0.1\u20133\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>, i.p. and 3\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>, p.o.) increased <jats:styled-content style=\"fixed-case\">WGT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">FPO<\/jats:styled-content> in mice and reversed experimental constipation. The effect of taranabant was absent in <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1<jats:sup>\u2212\/\u2212<\/jats:sup> mice. Taranabant significantly decreased the number of pain\u2010related behaviors in animal models. At the doses tested, taranabant did not display mood\u2010related adverse side effects typical for <jats:styled-content style=\"fixed-case\">CB<\/jats:styled-content>1 receptor inverse agonists.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>Taranabant improved symptoms related to slow <jats:styled-content style=\"fixed-case\">GI<\/jats:styled-content> motility and abdominal pain and may become an attractive template in the development of novel therapeutics targeting <jats:styled-content style=\"fixed-case\">IBS<\/jats:styled-content>\u2010C.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12158","type":"journal-article","created":{"date-parts":[[2013,5,22]],"date-time":"2013-05-22T01:26:21Z","timestamp":1369185981000},"source":"Crossref","is-referenced-by-count":28,"title":["The cannabinoid\u20101 receptor inverse agonist taranabant reduces abdominal pain and increases intestinal transit in mice"],"prefix":"10.1111","volume":"25","author":[{"given":"J.","family":"Fichna","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Gastroenterology University of Calgary Calgary AB Canada"},{"name":"Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"},{"name":"Department of Biomolecular Chemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Sibaev","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Gastroenterology Ludwig Maximilians University of Munich Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Sa\u0142aga","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Sobczak","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry Faculty of Medicine Medical University of Lodz Lodz Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Storr","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Gastroenterology University of Calgary Calgary AB Canada"},{"name":"Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"},{"name":"Department of Medicine Division of Gastroenterology Ludwig Maximilians University of Munich Munich 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