Suppression of food intake and food-reinforced behavior produced by the novel CB1 receptor antagonist/inverse agonist AM 1387

2006 ◽  
Vol 83 (3) ◽  
pp. 396-402 ◽  
Author(s):  
Peter J. McLaughlin ◽  
Liu Qian ◽  
JodiAnne T. Wood ◽  
Ania Wisniecki ◽  
Keisha M. Winston ◽  
...  
Keyword(s):  
Food Intake ◽  
Receptor Antagonist ◽  
Inverse Agonist ◽  
Cb1 Receptor ◽  
The Novel ◽  
Cb1 Receptor Antagonist

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

2003 ◽  
Vol 284 (2) ◽  
pp. R345-R353 ◽  
Author(s):  
Christine Ravinet Trillou ◽  
Michèle Arnone ◽  
Claire Delgorge ◽  
Nadine Gonalons ◽  
Peter Keane ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Day Treatment ◽  
Body Weight Loss ◽  
Cb1 Receptor ◽  
The Body ◽  
Sustained Reduction ◽  
Cb1 Receptor Antagonist ◽  
Plasma Leptin

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−1orally) 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.

scholarly journals Monoacylglycerol lipase inhibition attenuates acute and anticipatory nausea in rats

SURG Journal ◽  
2014 ◽  
Vol 7 (3) ◽  
pp. 21-29
Author(s):  
Rachel I. Downey ◽  
Cheryl L. Limebeer ◽  
Heather I. Morris ◽  
Linda A. Parker
Keyword(s):  
Receptor Antagonist ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Monoacylglycerol Lipase ◽  
Anticipatory Nausea ◽  
Acute Nausea ◽  
Sr 141716 ◽  
Cb1 Receptor Antagonist ◽  
Lipase Inhibition

This study investigates the role of the endocannabinoid 2-arachidonyl glycerol (2-AG) in regulating acute and anticipatory nausea in rats using the conditioned gaping model. The animals were systemically pretreated with MJN110, a selective monoacylglycerol lipase (MAGL) inhibitor, to enhance endogenous levels of 2-AG. Acute nausea was assessed using the taste reactivity model in which a flavour, saccharin, was paired with the administration of the emetic agent, lithium chloride (LiCl). Anticipatory nausea was assessed using a model of contextually elicited conditioned gaping in which a context was paired with the emetic agent, LiCl. Results indicated that MJN110 at the 10.0 mg kg-1 and 20.0 mg kg-1 dosage significantly attenuated acute and anticipatory nausea, as displayed by the significant reduction in mean number of gapes. This suppression was mediated by CB1 receptor activation as displayed by reversal of such effects when MJN110 was coadministered with the CB1 receptor antagonist, SR 141716. The results suggest that enhancement of endogenous 2-AG levels by MAGL inhibition may have anti-emetic potential. Keywords: 2-arachidonyl glycerol; monoacylglycerol lipase; endocannabinoid; nausea; conditioned gaping; CB1 receptor

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