Biomaterial Database

Rapid tolerance to the intestinal prokinetic effect of cannabinoid CB1 receptor antagonist, SR 141716 (Rimonabant). 2004

Mauro A M Carai, and Giancarlo Colombo, and Gian Luigi Gessa

Bernard B. Brodie Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari, Italy. macarai@unica.it

The cannabinoid CB(1) receptor antagonist, SR 141716 (Rimonabant), has been reported to stimulate, when acutely administered, intestinal motility in mice. The present study was aimed at determining whether tolerance develops to its repeated administration. Mice were treated twice a day for up to 8 consecutive days with 0, 3 and 5.6 mg/kg SR 141716 (i.p.). On days 1, 3, 5 and 8, separate groups of mice were treated intragastrically with a non-absorbable colored marker (carmine). The distance traveled by the head of the marker in the small intestine was recorded. On day 1, SR 141716 markedly activated intestinal peristalsis, but complete tolerance to this effect developed within the third day of treatment. The results may have some relevance to the proposed future clinical use of SR 141716.

UI	MeSH Term	Description	Entries
D007274	Injections, Intraperitoneal	Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall.	Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007422	Intestines	The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.	Intestine
D008297	Male		Males
D010528	Peristalsis	A movement, caused by sequential muscle contraction, that pushes the contents of the intestines or other tubular organs in one direction.	Peristalses
D010880	Piperidines	A family of hexahydropyridines.
D011720	Pyrazoles	Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004361	Drug Tolerance	Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.	Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D005769	Gastrointestinal Motility	The motor activity of the GASTROINTESTINAL TRACT.	Intestinal Motility,Gastrointestinal Motilities,Intestinal Motilities,Motilities, Gastrointestinal,Motilities, Intestinal,Motility, Gastrointestinal,Motility, Intestinal
D000077285	Rimonabant	A pyrazole and piperidine derivative that acts as a selective cannabinoid type-1 receptor (CB1 RECEPTOR) antagonist. It inhibits the proliferation and maturation of ADIPOCYTES, improves lipid and glucose metabolism, and regulates food intake and energy balance. It is used in the management of OBESITY.	Acomplia,N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride,Rimonabant Hydrochloride,SR 141716,SR 141716A,SR-141716A,SR141716,SR141716A,Zimulti