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Radiographic dose‐dependency study of loperamide effects on gastrointestinal motor function in the rat. Temporal relationship with nausea‐like behavior
Author(s) -
Vera Gema,
Girón Rocío,
MartínFontelles María Isabel,
Abalo Raquel
Publication year - 2019
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13621
Subject(s) - loperamide , nausea , medicine , stomach , vomiting , agonist , gastrointestinal function , pharmacology , gastroenterology , anesthesia , endocrinology , diarrhea , receptor
Background 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‐like behavior). Methods Male Wistar rats received an intraperitoneal injection of vehicle or loperamide (0.1, 1, or 10 mg kg −1 ). 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‐rays were taken 0‐8 hours 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 hours after administration, respectively. Key Results Loperamide significantly induced antinociception, hypothermia, and hypolocomotion (but not catalepsy) at high doses and dose‐dependently 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. Conclusions and inferences Our results suggest that loperamide‐induced nausea and gastric dysmotility might be temporally dissociated.