Tags

Type your tag names separated by a space and hit enter

The cannabinoid-1 receptor inverse agonist taranabant reduces abdominal pain and increases intestinal transit in mice.
Neurogastroenterol Motil. 2013 Aug; 25(8):e550-9.NM

Abstract

BACKGROUND

Constipation-predominant irritable bowel syndrome (IBS-C) is a common functional gastrointestinal (GI) disorder with abdominal pain and decreased motility. Current treatments of IBS-C are insufficient. The aim of this study was to evaluate the potential application of taranabant, a cannabinoid type 1 (CB1) inverse agonist using mouse models mimicking the symptoms of IBS-C.

METHODS

Changes in intestinal contractile activity were studied in vitro, using isolated mouse ileum and colon and intracellular recordings. In vivo, whole gastrointestinal transit (WGT) and fecal pellet output (FPO) were measured under standard conditions and with pharmacologically delayed GI transit. The antinociceptive effect was evaluated in mustard oil- and acetic acid-induced models of visceral pain. Forced swimming and tail suspension tests were performed and locomotor activity was measured to evaluate potential central side effects.

KEY RESULTS

In vitro, taranabant (10(-10) -10(-7) mol L(-1)) increased contractile responses in mouse ileum and blocked the effect of the CB agonist WIN 55,212-2. Taranabant had no effect on the amplitude of electrical field stimulation (EFS)-evoked junction potentials. In vivo, taranabant (0.1-3 mg kg(-1), i.p. and 3 mg kg(-1), p.o.) increased WGT and FPO in mice and reversed experimental constipation. The effect of taranabant was absent in CB1(-/-) mice. Taranabant significantly decreased the number of pain-related behaviors in animal models. At the doses tested, taranabant did not display mood-related adverse side effects typical for CB1 receptor inverse agonists.

CONCLUSIONS & INFERENCES

Taranabant improved symptoms related to slow GI motility and abdominal pain and may become an attractive template in the development of novel therapeutics targeting IBS-C.

Authors+Show Affiliations

Department of Medicine, Division of Gastroenterology, University of Calgary, Calgary, AB, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23692073

Citation

Fichna, J, et al. "The Cannabinoid-1 Receptor Inverse Agonist Taranabant Reduces Abdominal Pain and Increases Intestinal Transit in Mice." Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, vol. 25, no. 8, 2013, pp. e550-9.
Fichna J, Sibaev A, Sałaga M, et al. The cannabinoid-1 receptor inverse agonist taranabant reduces abdominal pain and increases intestinal transit in mice. Neurogastroenterol Motil. 2013;25(8):e550-9.
Fichna, J., Sibaev, A., Sałaga, M., Sobczak, M., & Storr, M. (2013). The cannabinoid-1 receptor inverse agonist taranabant reduces abdominal pain and increases intestinal transit in mice. Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society, 25(8), e550-9. https://doi.org/10.1111/nmo.12158
Fichna J, et al. The Cannabinoid-1 Receptor Inverse Agonist Taranabant Reduces Abdominal Pain and Increases Intestinal Transit in Mice. Neurogastroenterol Motil. 2013;25(8):e550-9. PubMed PMID: 23692073.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The cannabinoid-1 receptor inverse agonist taranabant reduces abdominal pain and increases intestinal transit in mice. AU - Fichna,J, AU - Sibaev,A, AU - Sałaga,M, AU - Sobczak,M, AU - Storr,M, Y1 - 2013/05/21/ PY - 2013/02/12/received PY - 2013/04/26/accepted PY - 2013/5/23/entrez PY - 2013/5/23/pubmed PY - 2014/3/5/medline KW - abdominal pain KW - cannabinoid receptor inverse agonist KW - constipation KW - endogenous cannabinoid system KW - irritable bowel syndrome SP - e550 EP - 9 JF - Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society JO - Neurogastroenterol Motil VL - 25 IS - 8 N2 - BACKGROUND: Constipation-predominant irritable bowel syndrome (IBS-C) is a common functional gastrointestinal (GI) disorder with abdominal pain and decreased motility. Current treatments of IBS-C are insufficient. The aim of this study was to evaluate the potential application of taranabant, a cannabinoid type 1 (CB1) inverse agonist using mouse models mimicking the symptoms of IBS-C. METHODS: Changes in intestinal contractile activity were studied in vitro, using isolated mouse ileum and colon and intracellular recordings. In vivo, whole gastrointestinal transit (WGT) and fecal pellet output (FPO) were measured under standard conditions and with pharmacologically delayed GI transit. The antinociceptive effect was evaluated in mustard oil- and acetic acid-induced models of visceral pain. Forced swimming and tail suspension tests were performed and locomotor activity was measured to evaluate potential central side effects. KEY RESULTS: In vitro, taranabant (10(-10) -10(-7) mol L(-1)) increased contractile responses in mouse ileum and blocked the effect of the CB agonist WIN 55,212-2. Taranabant had no effect on the amplitude of electrical field stimulation (EFS)-evoked junction potentials. In vivo, taranabant (0.1-3 mg kg(-1), i.p. and 3 mg kg(-1), p.o.) increased WGT and FPO in mice and reversed experimental constipation. The effect of taranabant was absent in CB1(-/-) mice. Taranabant significantly decreased the number of pain-related behaviors in animal models. At the doses tested, taranabant did not display mood-related adverse side effects typical for CB1 receptor inverse agonists. CONCLUSIONS & INFERENCES: Taranabant improved symptoms related to slow GI motility and abdominal pain and may become an attractive template in the development of novel therapeutics targeting IBS-C. SN - 1365-2982 UR - https://www.unboundmedicine.com/medline/citation/23692073/The_cannabinoid_1_receptor_inverse_agonist_taranabant_reduces_abdominal_pain_and_increases_intestinal_transit_in_mice_ L2 - https://doi.org/10.1111/nmo.12158 DB - PRIME DP - Unbound Medicine ER -