Update on antiobesity drugs

The Society for Medicines Research organized a one-day meeting on antiobesity drugs on March 26, 1998, in London. Current environmental risks for obesity include an increase in the proportion of fat consumption--especially an increase in the fat-to-carbohydrate ratio--and an increase in a sedentary life-style without an appropriate lowering in food intake. Energy balance plays a pivotal role of in the control of body stores. Knowing the mechanisms of the control of energy intake and energy expenditure provides explanations for the incidence of obesity and also possible sites for drug intervention. The genetic basis for obesity is complex, with the probability of a number of interacting genes being involved (polygenic inheritance). Each of the main components of the energy balance relationship has a distinct genetic basis. The ob gene was first identified in 1994 by Friedman, and its product is leptin, which may well be a potential target for obesity treatment. Speakers at the meeting highlighted various targets that hold promise in developing pharmacological treatments for obesity: increasing the activity of satiety factors (CCK-8, GPL-1, ACTH, alphaMSH and 5-HT acting on 5-HT(2C) receptors); inhibiting orexigenic agents (NPY, MCH, galanin); targeting thermogenesis (beta(3)-adrenergic agonists and uncoupling proteins); targeting fat absorption; and targeting neuropeptides. Some of the compounds developed to act on these sites are now becoming available.