Rapid tolerance to the intestinal prokinetic effect of cannabinoid CB1 receptor antagonist, SR 141716 (Rimonabant).
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.
Carai
Mauro A M
MA
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari, Italy. macarai@unica.it
Colombo
Giancarlo
G
Gessa
Gian Luigi
GL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005769:Gastrointestinal Motility / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007422:Intestines / Q000187:drug effects*; D008297:Male; D051379:Mice; D010528:Peristalsis / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D013268:Stimulation, Chemical
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant