English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/44288
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

Central versus peripheral antagonism of cannabinoid CB1 receptor in obesity: Effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist, in Zucker rats

AuthorsPavón, F. J.; Serrano, A.; Pérez-Valero, V.; Jagerovic, Nadine ; Hernández-Folgado, Laura ; Bermúdez-Silva, Francisco Javier; Macías, M.; Goya, Pilar ; Fonseca, F. R. de
KeywordsCB1
cannabinoid antagonist
Zucker
feeding
SCD-1
Issue DateMay-2008
PublisherJohn Wiley & Sons
CitationJournal of Neuroendocrinology 20 (1) : 116-123 (2008)
AbstractThe endogenous cannabinoid system plays an important modulatory role in feeding behaviour and metabolism, acting at both central and peripheral levels. Chronic administration of cannabinoid CB1 receptor antagonists has been found to be effective in experimental obesity. However, clinically available cannabinoid receptor antagonists are inverse agonists that can target CB1 receptors located in both central circuits regulating appetite and motivation and in peripheral organs regulating metabolism and energy expenditure. This profile complicates understanding of cannabinoid CB1 receptor blockade as a therapeutic strategy in obesity and metabolic disorders. This review aims to explore the relevance of both inverse agonism and peripheral cannabinoid receptor blockade on the beneficial actions of chronic cannabinoid receptor blockade, by comparing the actions of the reference antagonist ⁄ inverse agonist rimonabant and the newly designed drug LH-21. LH-21 is a triazol derivative and a neutral cannabinoid receptor antagonist; it has a poor penetration rate into the central nervous system. When given acutely it decreases food intake and enhances the anorectic actions of oleoylethanolamide, a feeding suppressant lipid that acts on peripheral sensory terminals in a similar way as rimonabant. Unlike rimonabant, chronic administration of LH-21 (3 mg ⁄ kg) reduces feeding but does not improve hypertriglyceridaemia or hypercholesterolaemia; nor does it reduce liver fat deposits in Zucker rats. These results suggest that the inverse agonism and ⁄ or the antagonism of central cannabinoid CB1 receptors are necessary for the metabolic benefits of cannabinoid CB1 receptor blockade, but not for the appetite reduction
Publisher version (URL)http://dx.doi.org/10.1111/j.1365-2826.2008.01693.x
URIhttp://hdl.handle.net/10261/44288
DOI10.1111/j.1365-2826.2008.01693.x
ISSN0953-8194
Appears in Collections:(IQM) Artículos
Files in This Item:
There are no files associated with this item.
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.