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18426510

Source:http://linkedlifedata.com/resource/pubmed/id/18426510

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pubmed-article:18426510pubmed:dateCreated2008-4-22lld:pubmed
pubmed-article:18426510pubmed:abstractTextThe endogenous cannabinoid system plays an important modulatory role in feeding behaviour and metabolism, acting at both central and peripheral levels. Chronic administration of cannabinoid CB(1) receptor antagonists has been found to be effective in experimental obesity. However, clinically available cannabinoid receptor antagonists are inverse agonists that can target CB(1) 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 CB(1) 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 CB(1) receptors are necessary for the metabolic benefits of cannabinoid CB(1) receptor blockade, but not for the appetite reduction.lld:pubmed
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pubmed-article:18426510pubmed:articleTitleCentral versus peripheral antagonism of cannabinoid CB1 receptor in obesity: effects of LH-21, a peripherally acting neutral cannabinoid receptor antagonist, in Zucker rats.lld:pubmed
pubmed-article:18426510pubmed:affiliationFundación IMABIS, Hospital Carlos Haya, Av Carlos Haya 82, Málaga, Spain.lld:pubmed
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pubmed-article:18426510pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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