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In vitro and non‐invasive in vivo effects of the cannabinoid‐1 receptor agonist AM 841 on gastrointestinal motor function in the rat
Author(s) -
Abalo R.,
Chen C.,
Vera G.,
Fichna J.,
Thakur G. A.,
LópezPérez A. E.,
Makriyannis A.,
MartínFontelles M. I.,
Storr M.
Publication year - 2015
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.12668
Subject(s) - am251 , cannabinoid receptor agonists , cannabinoid , cannabinoid receptor , in vivo , agonist , pharmacology , cannabinoid receptor type 2 , receptor , gastrointestinal function , cannabinoid receptor antagonist , chemistry , gastric emptying , endocrinology , medicine , biology , biochemistry , stomach , microbiology and biotechnology
Background Cannabinoids have been traditionally used for the treatment of gastrointestinal ( GI ) symptoms, but the associated central effects, through cannabinoid‐1 receptors ( CB 1R), constitute an important drawback. Our aims were to characterize the effects of the recently developed highly potent long‐acting megagonist AM 841 on GI motor function and to determine its central effects in rats. Methods Male Wistar rats were used for in vitro and in vivo studies. The effect of AM 841 was tested on electrically induced twitch contractions of GI preparations ( in vitro ) and on GI motility measured radiographically after contrast administration ( in vivo ). Central effects of AM 841 were evaluated using the cannabinoid tetrad. The non‐selective cannabinoid agonist WIN 55,212‐2 ( WIN ) was used for comparison. The CB 1R ( AM 251) and CB 2R ( AM 630) antagonists were used to characterize cannabinoid receptor‐mediated effects of AM 841. Key Results AM 841 dose‐dependently reduced in vitro contractile activity of rat GI preparations via CB 1R, but not CB 2R or opioid receptors. In vivo , AM 841 acutely and potently reduced gastric emptying and intestinal transit in a dose‐dependent and AM 251‐sensitive manner. The in vivo GI effects of AM 841 at 0.1 mg/kg were comparable to those induced by WIN at 5 mg/kg. However, at this dose, AM 841 did not induce any sign of the cannabinoid tetrad, whereas WIN induced significant central effects. Conclusions & Inferences The CB 1R megagonist AM 841 may potently depress GI motor function in the absence of central effects. This effect may be mediated peripherally and may be useful in the treatment of GI motility disorders.