The potential use of selective 5-HT2C agonists in treating obesity

  title={The potential use of selective 5-HT2C agonists in treating obesity},
  author={Brian M. Smith and William J. Thomsen and Andrew J. Grottick},
  journal={Expert Opinion on Investigational Drugs},
  pages={257 - 266}
Activation of central 5-HT2C receptors as a strategy for appetite suppression and weight control is supported by animal pharmacology and human clinical studies. Considerable evidence comes from the weight-loss effects of fenfluramine, a non-selective 5-HT2C agonist. Advances in molecular pharmacology have led to an understanding of the effects of 5-HT2C receptor activation on food intake and satiety, in addition to providing insight into the causes of cardiac valvular insufficiency and… 

Pharmacological targeting of the serotonergic system for the treatment of obesity

Serotonergic compounds reducing ingestive behaviour are reviewed and their clinical potential for the treatment of obesity is discussed.

Targeting 5-HT receptors for the treatment of obesity.

Synthesis and SAR of potent and selective tetrahydropyrazinoisoquinolinone 5-HT(2C) receptor agonists.

Discovery and development of 5-HT(₂C) receptor agonists for obesity: is there light at the end of the tunnel?

The success of future 5-HT(₂C) agonists will depend on further improvements in selectivity (or attainment of complete specificity) and pharmaceutical properties to permit greater and sustained receptor stimulation, while avoiding side effects associated with the activation of other 5- HT receptors.

Appetite suppressants, cardiac valve disease and combination pharmacotherapy.

The evidence that cardiac valve disease involves activation of mitogenic serotonin 2B (5-HT2B) receptors by norfenfluramine, the major metabolite of fenfluramines, is discussed.

Identification of Novel 1-O-substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists.

The findings may serve as good starting points for the development of more potent and selective 5-HT2C agonists as valuable pharmacological tools or potential drug candidates.

Lorcaserin: an investigational serotonin 2C agonist for weight loss.

  • Kathryn M. HurrenH. Berlie
  • Medicine
    American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
  • 2011
Lorcaserin, a 5-HT(2C) agonist, has demonstrated efficacy in patients who are obese or are overweight with associated comorbidities, and Phase III trials have found that more than 35% of patients lost greater than 5% of their baseline weight.

Serotonergic drugs and valvular heart disease

A more likely cause of fenfluramines-induced valvulopathy is activation of 5-HT2B receptors on heart valves by the metabolite norfenfluramine, and future serotonergic medications should be designed to lack 5- HT2B agonist activity.



Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity.

  • K. Miller
  • Medicine, Biology
    Molecular interventions
  • 2005
Development of highly selective 5-HT(2C) agonists may recapitulate the clinical anti-obesity properties observed with fenfluramine while avoiding the significant cardiovascular and pulmonary side effects.

5-HT2C receptor agonists as potential drugs for the treatment of obesity.

  • M. Bickerdike
  • Biology, Psychology
    Current topics in medicinal chemistry
  • 2003
Both the pre-clinical and clinical evidence supporting the use of 5-HT(2C) receptor agonists for the treatment of obesity is reviewed and the developments that have been made to date are assessed.

New 5-HT2C receptor agonists

This review will focus on recent patent applications through August 2003 that describe compounds that have agonist activity at the 5-HT2C receptor, and should be complementary to previous Expert Opinion discussions on the5-HT1C receptor.

5-HT2C receptor activation decreases appetite and body weight in obese subjects

It is suggested that during 2 weeks treatment in humans, mCPP may continue to activate brain 5-HT2C receptors, and that this effect is associated with decreases in appetite and body weight.

5-HT 2C Receptor Agonists for the Treatment of Obesity. Biological and Chemical Adventures

Introduction of a (2S)-aminopropyl group in place of the aminoethyl endogenous ligand side-chain enhanced the affinity at the 5-HT 2 C receptor and reduced affinity towards monoamine oxidase enzymes (MAO).

Discovery and SAR of new benzazepines as potent and selective 5-HT(2C) receptor agonists for the treatment of obesity.

Function of the serotonin 5-hydroxytryptamine 2B receptor in pulmonary hypertension

Using the chronic-hypoxic-mouse model of pulmonary hypertension, it is found that the hypoxia-dependent increase in pulmonary blood pressure and lung remodeling are associated with an increase in vascular proliferation, elastase activity and transforming growth factor-β levels, and that these parameters are potentiated by dexfenfluramine treatment.

The role of 5-HT2C receptors in affective disorders.

Results are consistent with an important hypothesis proposing that 5-HT has a complex, dual action on the neural mechanism of anxiety by either facilitating or inhibiting different kinds of anxiety in different brain regions and suggest that5-HT(2C) receptor subtypes play an important role in the therapeutic properties of SSRIs.

Reduced satiating effect of d-fenfluramine in serotonin 5-HT2C receptor mutant mice

A role for the 5-HT2C receptor in mediating d-fenfluramine-induced satiety is demonstrated and is demonstrated to be a potent inhibitor of the re-uptake of5-HT into nerve terminals and a facilitator of behavioural satiety in mutant mice.

Eating disorder and epilepsy in mice lacking 5-HT2C serotonin receptors

It is shown that 5-HT2C receptor-deficient mice are overweight as a result of abnormal control of feeding behaviour, establishing a role for this receptor in the serotonergic control of appetite.