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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Serotonergic drugs : effects on appetite expression and use for the treatment of obesity.

Over 35 years of research suggests that endogenous hypothalamic serotonin (5-hydroxytryptamine) plays an important part in within-meal satiation and post-meal satiety processes. Thus, the serotonin system has provided a viable target for weight control, critical to the action of at least two effective anti-obesity treatments, both producing clinically significant weight loss over a year or more. Numerous serotonin receptor subtypes have been identified; of these, serotonin 5-HT(1B) and 5-HT(2C) receptors have been specifically recognised as mediators of serotonin-induced satiety.A number of serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs), dexfenfluramine and 5-HT(2C) receptor agonists, have been shown to significantly attenuate rodent bodyweight gain. This effect is strongly associated with marked hypophagia and is probably mediated by the hypothalamic melanocortin system. Additionally, sibutramine, dexfenfluramine, fluoxetine and the 5-HT(2C) receptor agonist chlorophenylpiperazine (mCPP) have all been shown to modify appetite in both lean and obese humans, resulting in reduced caloric intake. Clinical studies demonstrate serotonergic drugs specifically reduce appetite prior to and following the consumption of fixed caloric loads, and cause a reduction in pre-meal appetite and caloric intake at ad libitum meals. Weight loss in the obese has also been produced by treatment with both the serotonin precursor 5-hydroxytryptophan and the preferential 5-HT(2C) receptor agonist mCPP.A new generation of 5-HT(2C) receptor selective agonists have been developed and at least one, lorcaserin (APD356), is currently undergoing clinical trials. In addition, 5-HT(6) receptor antagonists such as PRX-07034 and BVT74316 have been shown to potently reduce food intake and bodyweight gain in rodent models and have recently entered clinical trials. However, the role of the 5-HT(6) receptor in the expression of appetite remains to be determined. The hope is that these drugs will not only be free of their predecessors' adverse effect profiles, but will also be equally or more effective at regulating appetite and controlling bodyweight.[1]

References

  1. Serotonergic drugs : effects on appetite expression and use for the treatment of obesity. Halford, J.C., Harrold, J.A., Boyland, E.J., Lawton, C.L., Blundell, J.E. Drugs (2007) [Pubmed]
 
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