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

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 pulmonary hypertension associated with the use of fenfluramine. However, clinically validated animal models of drug-induced disease and knowledge of the molecular mechanisms of these safety issues is lacking. For this reason, the development of selective 5-HT2C agonists for the treatment of obesity has remained a challenge.