Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice

Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R345-53. doi: 10.1152/ajpregu.00545.2002. Epub 2002 Oct 24.


Because the CB1 receptor antagonist SR141716 was previously reported to modulate food intake in rodents, we studied its efficacy in reducing obesity in a diet-induced obesity (DIO) model widely used for research on the human obesity syndrome. During a 5-wk treatment, SR141716 (10 mg. kg(-1). day(-1) orally) induced a transient reduction of food intake (-48% on week 1) and a marked but sustained reduction of body weight (-20%) and adiposity (-50%) of DIO mice. Furthermore, SR141716 corrected the insulin resistance and lowered plasma leptin, insulin, and free fatty acid levels. Most of these effects were present, but less pronounced at 3 mg. kg(-1). day(-1). In addition to its hypophagic action, SR141716 may influence metabolic processes as the body weight loss of SR141716-treated mice was significantly higher during 24-h fasting compared with vehicle-treated animals, and when a 3-day treatment was compared with a pair feeding. SR141716 had no effect in CB1 receptor knockout mice, which confirmed the implication of CB1 receptors in the activity of the compound. These findings suggest that SR141716 has a potential as a novel anti-obesity treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Body Weight / drug effects
  • Diet*
  • Dietary Fats / administration & dosage
  • Dietary Fats / pharmacology
  • Dose-Response Relationship, Drug
  • Fatty Acids, Nonesterified / blood
  • Insulin / blood
  • Leptin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / blood
  • Obesity / chemically induced
  • Obesity / drug therapy*
  • Obesity / physiopathology
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use*
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use*
  • Receptors, Cannabinoid
  • Receptors, Drug / antagonists & inhibitors*
  • Receptors, Drug / genetics
  • Receptors, Drug / metabolism
  • Rimonabant
  • Time Factors


  • Dietary Fats
  • Fatty Acids, Nonesterified
  • Insulin
  • Leptin
  • Piperidines
  • Pyrazoles
  • Receptors, Cannabinoid
  • Receptors, Drug
  • Rimonabant