{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:11:18Z","timestamp":1780377078484,"version":"3.54.1"},"reference-count":86,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2012-40075-C02-01"],"award-info":[{"award-number":["SAF2012-40075-C02-01"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Loperamide is a potent mu opioid receptor agonist available over the counter to treat diarrhea. Although at therapeutic doses loperamide is devoid of central effects, it may exert them if used at high doses or combined with drugs that increase its systemic and\/or central bioavailability. Recently, public health and scientific interest on loperamide has increased due to a growing trend of misuse and abuse, and consequent reports on its toxicity. Our aim was to evaluate in the rat the effects of increasing loperamide doses, with increasing likelihood to induce central effects, on gastrointestinal motor function (including gastric dysmotility and nausea\u2010like behavior).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male Wistar rats received an intraperitoneal injection of vehicle or loperamide (0.1, 1, or 10\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>). Three sets of experiments were performed to evaluate: (a) central effects (somatic nociceptive thresholds, immobility time, core temperature, spontaneous locomotor activity); (b) general gastrointestinal motility (serial X\u2010rays were taken 0\u20108\u00a0hours after intragastric barium administration and analyzed semiquantitatively, morphometrically, and densitometrically); and (c) bedding intake (a rodent indirect marker of nausea). Animals from sets 1 and 3 were used to evaluate gastric dysmotility ex vivo at 2 and 4\u00a0hours after administration, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Loperamide significantly induced antinociception, hypothermia, and hypolocomotion (but not catalepsy) at high doses and dose\u2010dependently reduced gastrointestinal motor function, with the intestine exhibiting higher sensitivity than the stomach. Whereas bedding intake occurred early and transiently, gastric dysmotility was much more persistent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and inferences<\/jats:title><jats:p>Our results suggest that loperamide\u2010induced nausea and gastric dysmotility might be temporally dissociated.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13621","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T23:54:22Z","timestamp":1558569262000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Radiographic dose\u2010dependency study of loperamide effects on gastrointestinal motor function in the rat. Temporal relationship with nausea\u2010like behavior"],"prefix":"10.1111","volume":"31","author":[{"given":"Gema","family":"Vera","sequence":"first","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud Universidad Rey Juan Carlos Alcorc\u00f3n Spain"},{"name":"Grupo de Excelencia Investigadora URJC\u2010Banco de Santander\u2010Grupo Multidisciplinar de Investigaci\u00f3n y Tratamiento del Dolor (i+DOL) Alcorc\u00f3n Spain"},{"name":"Unidad Asociada I+D+i al Instituto de Qu\u00edmica M\u00e9dica (IQM) Centro Superior de Investigaciones Cient\u00edficas (CSIC) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"Gir\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias B\u00e1sicas de la Salud, Facultad de Ciencias de la Salud Universidad Rey Juan Carlos Alcorc\u00f3n Spain"},{"name":"Grupo de Excelencia Investigadora URJC\u2010Banco de Santander\u2010Grupo 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