Serotonin And Satiety: Targets For Drug Discovery

The role of serotonin in the control of overweight and obesity iswell-established, although its precise mechanism remains unknown. Now, the UK specialist neuroscience company, Cerebrus, has reported new data which suggest that the serotonin 5-HT2C receptor may play a key role in governing satiety.

Serotonin-modulating drugs such as fenfluramine and its isomer dexfenfluramine have been used in the management of obesity for many years, and have been shown to decrease body weight over extended periods of time, providing patients continue on the drug. Unfortunately, these drugs have a wide and non-specific action, stimulating serotonin release and inhibiting its reuptake, and this broad activity is thought to be responsible for some of their side effects.

Dexfenfluramine, launched in the USA last year after a considerable delay, likely in response to alarming data on the incidence of obesity and overweight, is controversial because it has been associated with a risk of primary pulmonary hypertension, while results from animal studies have shown patterns of neuron loss which suggest neurotoxicity. Wyeth-Ayerst and Servier, which market the drug, point to its use for many years in Europe as evidence that these concerns are unjustified and that the benefits of the drug in the obese outweigh its side effects.