Authors: S. P. Vickers; G. A. Kennett

Source: Current Drug Targets, Volume 6, Number 2, March 2005 , pp. 215-223(9)

Publisher: Bentham Science Publishers

Abstract:

Over past centuries, Cannabis sativa (9-tetrahydrocannabinol being the principal active ingredient) has been used extensively for both medicinal and recreational uses, and one widely reported effect is the onset of a ravenous appetite and eating behaviour. The pharmacological properties of such exogenous cannabinoids are mediated through the activation of two receptor subtypes, the CB1 and CB2 receptors. A number of endogenous ligands for these receptors, the endocannabinoids, have now also been identified allowing their effects on ingestive behaviour to be determined.

In a number of species, including man, the administration of exogenous and endogenous cannabinoids leads to robust increases in food intake and can promote body weight gain. These effects are believed to be mediated through activation of the CB1 receptor. Conversely, experiments with selective CB1 receptor antagonists have demonstrated reductions in food intake and body weight with repeated compound administration. These reductions in body weight appear to be greater in obese animals and may be the result of a dual effect on both food intake and metabolic processes.

Such findings have led to a number of pharmaceutical companies developing selective CB1 receptor antagonists for the treatment of obesity. The most advanced compound is Sanofi-Synthelabo;s inverse agonist, rimonabant (Acomplia; SR- 141716), and early Phase III results have recently demonstrated significant reductions in body weight, waist circumference and improvement of lipid and glucose metabolism in overweight and obese humans. Accordingly, the cannabinoid system appears to have an important role in the regulation of ingestive behaviour in man and animals.

Keywords: endocannabinoids; obesity; rimonabant; sr-141716; appetite; review

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389450053174514

Affiliations: 1: RenaSci Consultancy Ltd., BioCity Nottingham, Pennyfoot Street, Nottingham. NG1 1GF, UK.

Publication date: 2005-03-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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