Document Detail


Cannabinoid CB1 receptor inverse agonists and neutral antagonists: effects on food intake, food-reinforced behavior and food aversions.
MedLine Citation:
PMID:  17521686     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Drugs that interfere with cannabinoid CB1 receptor transmission suppress a number of food-related behaviors, and these compounds are currently being assessed for their potential utility as appetite suppressants. In addition to rimonabant (SR141716A), several other compounds have been evaluated, including AM251 and AM1387. Biochemical studies indicate that most of the drugs assessed thus far have been CB1 inverse agonists, and these drugs all act to suppress food intake and disrupt food-reinforced behavior. Behavioral tests involving intake of different diets (i.e., high fat, high carbohydrate, laboratory chow) indicate that consumption of all three food types is disrupted by CB1 inverse agonists, and that, expressed as a percent of baseline intake, the effect is roughly comparable across different diets. Although CB1 inverse agonists do not appear to produce severe motor impairments that disrupt feeding behavior, there is evidence that they can induce nausea and malaise. Recent studies have been undertaken to characterize the behavioral effects of CB1 receptor neutral antagonists such as AM4113 to determine if these drugs can reduce feeding and food-reinforced behaviors. Across a variety of different tests, AM4113 produces effects on food-motivated behavior that are very similar to those produced by CB1 inverse agonists. Moreover, this drug did not induce conditioned gaping in rats or vomiting in ferrets. These results suggest that CB1 receptor neutral antagonists may decrease appetite by blocking endogenous cannabinoid tone, and that these drugs may be less associated with nausea than is the case for CB1 inverse agonists.
Authors:
John D Salamone; Peter J McLaughlin; Kelly Sink; Alexandros Makriyannis; Linda A Parker
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2007-04-14
Journal Detail:
Title:  Physiology & behavior     Volume:  91     ISSN:  0031-9384     ISO Abbreviation:  Physiol. Behav.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-09     Completed Date:  2007-09-26     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0151504     Medline TA:  Physiol Behav     Country:  United States    
Other Details:
Languages:  eng     Pagination:  383-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Avoidance Learning / drug effects*
Behavior, Animal / drug effects
Eating / drug effects*
Feeding Behavior / drug effects
Food*
Humans
Pyrazoles / pharmacology*
Rats
Receptor, Cannabinoid, CB1* / agonists,  antagonists & inhibitors,  physiology
Reinforcement (Psychology)*
Grant Support
ID/Acronym/Agency:
P01 DA009158/DA/NIDA NIH HHS; P01 DA009158-08/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Pyrazoles; 0/Receptor, Cannabinoid, CB1
Comments/Corrections

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