Research article summary (published 28 Oct 2007):

Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders.

Full Abstract

The increasing global prevalence of obesity unequivocally demonstrates that neither behavioural (diet and exercise) nor pharmacological approaches to this health problem are working. In this area of high unmet clinical need, the 5-HT6 receptor has generated enormous interest amongst academic and pharmaceutical industry scientists as a molecular target for the development of a new generation of safe and more effective anti-obesity drugs. In this review, we have described the major developments that have occurred in the fields of the medicinal chemistry and pharmacology of 5-HT6 ligands, with particular emphasis on their potential application as novel anti-obesity drugs. The last 5 years have witnessed an increasing understanding of the 5-HT6 receptor and its structural requirements that has produced an explosion in the number and diversity of novel, highly selective 5-HT6 receptor agonists, partial agonists and antagonists that have been designed and synthesized. In animal models, 5-HT6 receptor ligands of all functional types have been shown to decrease food intake when given acutely and chronically, to evoke profound and sustained weight-loss in obese animals, and concomitantly to improve a number of cardio-metabolic risk factors. Comparator studies in obese animal models, which are highly predictive of clinical outcomes, indicate that 5-HT6 ligands may have the potential to be more efficacious in the treatment of obesity than the current generation of anti-obesity drugs.

Author information

Author/s: Heal, D J (DJ); Smith, S L (SL); Fisas, A (A); Codony, X (X); Buschmann, H (H);

Affiliation: RenaSci Consultancy Ltd, BioCity, Nottingham, NG1 1GF, UK. david.heal(-atsign-)renasci.co.uk <david.heal(-atsign-)renasci.co.uk>

Journal and publication information

Publication Type: Journal Article; Review

Journal: Pharmacology & therapeutics (Pharmacol Ther), published in England. (Language: eng)

Reference: 2008-Feb; vol 117 (issue 2) : pp 207-31

Dates: Created 2008/01/28; Completed 2008/03/27;

PMID: 18068807, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Anti-Obesity Agents - adverse effects; chemistry; pharmacology Body Weight - drug effects Central Nervous System - drug effects; metabolism Disease Models, Animal Drug Partial Agonism Eating - drug effects Humans Ligands Metabolic Syndrome X - drug therapy; epidemiology; etiology; metabolism; physiopathology

Metabolic Syndrome X - drug therapy; epidemiology; etiology; metabolism; physiopathology Molecular Structure Obesity - complications; drug therapy; epidemiology; metabolism; physiopathology Receptors, Serotonin - drug effects; metabolism Satiety Response - drug effects Serotonin Agonists - adverse effects; chemistry; pharmacology Serotonin Antagonists - adverse effects; chemistry; pharmacology Structure-Activity Relationship Treatment Outcome Weight Loss

Associated Chemicals: Anti-Obesity Agents (0) ; Ligands (0) ; Receptors, Serotonin (0) ; Serotonin Agonists (0) ; Serotonin Antagonists (0) ; serotonin 6 receptor (0)

Related articles

These are the highest related articles currently in the database:

• Pharmacophore models for metabotropic 5-HT receptor ligands. 30 Dec 2005
• Manipulating central nervous mechanisms of food intake and body weight regulation by intranasal administration of neuropeptides in man. 28 Oct 2004
• Stereoselective pharmacological effects of lysergic acid amides possessing chirality in the amide substituent. 30 Dec 1995
• Neuropeptide Y2 receptors as drug targets for the central regulation of body weight. 29 Sep 2005
• Molecular design based on 3D-pharmacophore. Application to 5-HT4 receptor. 29 Jun 2002
• Selective agents for serotonin2C (5-HT2C) receptor. 30 Dec 2005
• Emerging aspects of pharmacotherapy for obesity and metabolic syndrome. 30 Oct 2004
• Interaction of 1,2,4-substituted piperazines, new serotonin receptor ligands, with 5-HT1A and 5-HT2A receptors. 30 Mar 2002
• New esters of 4-amino-5-chloro-2-methoxybenzoic acid as potent agonists and antagonists for 5-HT4 receptors. 12 Feb 1997
• Anti-obesity drugs. 30 May 2008

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.