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Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice.
J Pharmacol Exp Ther. 2010 Sep 01; 334(3):973-80.JP

Abstract

The endocannabinoid system is involved in the regulation of gastrointestinal (GI) motility and inflammation. Using the peripherally restricted cannabinoid (CB)(1)/CB(2) receptor agonist naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), we investigated the role of peripheral cannabinoid receptors in the regulation of GI motility and the development of colitis in mice. The actions of SAB378 on whole gut transit, upper GI transit, colonic propulsion, and locomotor activity were investigated in C57BL/6N, CB(1) receptor knockout, and CB(2) receptor knockout mice. The potential for SAB378 to modify inflammation was studied by using dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) models of experimental colitis. SAB378 did not modify locomotor activity. SAB378 slowed all parameters of GI motility, and these effects were significantly reduced by the CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide (AM251), but not by the CB(2) receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H- indol-3-yl](4-methoxyphenyl)methanone (AM630). SAB378 did not inhibit GI transit or colonic propulsion in CB(1) receptor knockout mice, whereas its effects were observed in CB(2) receptor knockout mice. SAB378 did not reduce the degree of colitis induced by DSS or TNBS. The actions of SAB378 on GI motility are mediated by peripherally located CB(1) receptors. SAB378 was not effective against two models of experimental colitis, which may indicate that peripheral cannabinoid receptor stimulation alone may not be sufficient to mediate the anti-inflammatory effects of cannabinoids.

Authors+Show Affiliations

Hotchkiss Brain Institute and Snyder Institute of Infection, Immunity, and Inflammation, Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.No affiliation info availableNo 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

20571060

Citation

Cluny, Nina L., et al. "Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a Peripherally Restricted Cannabinoid CB1/CB2 Receptor Agonist, Inhibits Gastrointestinal Motility but Has No Effect On Experimental Colitis in Mice." The Journal of Pharmacology and Experimental Therapeutics, vol. 334, no. 3, 2010, pp. 973-80.
Cluny NL, Keenan CM, Duncan M, et al. Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice. J Pharmacol Exp Ther. 2010;334(3):973-80.
Cluny, N. L., Keenan, C. M., Duncan, M., Fox, A., Lutz, B., & Sharkey, K. A. (2010). Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice. The Journal of Pharmacology and Experimental Therapeutics, 334(3), 973-80. https://doi.org/10.1124/jpet.110.169946
Cluny NL, et al. Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a Peripherally Restricted Cannabinoid CB1/CB2 Receptor Agonist, Inhibits Gastrointestinal Motility but Has No Effect On Experimental Colitis in Mice. J Pharmacol Exp Ther. 2010 Sep 1;334(3):973-80. PubMed PMID: 20571060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), a peripherally restricted cannabinoid CB1/CB2 receptor agonist, inhibits gastrointestinal motility but has no effect on experimental colitis in mice. AU - Cluny,Nina L, AU - Keenan,Catherine M, AU - Duncan,Marnie, AU - Fox,Alyson, AU - Lutz,Beat, AU - Sharkey,Keith A, Y1 - 2010/06/22/ PY - 2010/6/24/entrez PY - 2010/6/24/pubmed PY - 2010/9/24/medline SP - 973 EP - 80 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 334 IS - 3 N2 - The endocannabinoid system is involved in the regulation of gastrointestinal (GI) motility and inflammation. Using the peripherally restricted cannabinoid (CB)(1)/CB(2) receptor agonist naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (SAB378), we investigated the role of peripheral cannabinoid receptors in the regulation of GI motility and the development of colitis in mice. The actions of SAB378 on whole gut transit, upper GI transit, colonic propulsion, and locomotor activity were investigated in C57BL/6N, CB(1) receptor knockout, and CB(2) receptor knockout mice. The potential for SAB378 to modify inflammation was studied by using dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) models of experimental colitis. SAB378 did not modify locomotor activity. SAB378 slowed all parameters of GI motility, and these effects were significantly reduced by the CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide (AM251), but not by the CB(2) receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H- indol-3-yl](4-methoxyphenyl)methanone (AM630). SAB378 did not inhibit GI transit or colonic propulsion in CB(1) receptor knockout mice, whereas its effects were observed in CB(2) receptor knockout mice. SAB378 did not reduce the degree of colitis induced by DSS or TNBS. The actions of SAB378 on GI motility are mediated by peripherally located CB(1) receptors. SAB378 was not effective against two models of experimental colitis, which may indicate that peripheral cannabinoid receptor stimulation alone may not be sufficient to mediate the anti-inflammatory effects of cannabinoids. SN - 1521-0103 UR - https://www.unboundmedicine.com/medline/citation/20571060/Naphthalen_1_yl__4_pentyloxynaphthalen_1_yl_methanone__SAB378__a_peripherally_restricted_cannabinoid_CB1/CB2_receptor_agonist_inhibits_gastrointestinal_motility_but_has_no_effect_on_experimental_colitis_in_mice_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=20571060 DB - PRIME DP - Unbound Medicine ER -