Chapter 20. The Pharmacological Treatment of Obesity

Publisher Summary The treatment of obesity has, however, proven difficult because of the redundancy built into the body weight regulatory mechanism. Consequently, when one system is perturbed, there is often a compensatory reaction that minimizes or negates the initial effect. It may be necessary to treat obese patients with agents that act by more than one mechanism or with a combination of therapeutics that decrease energy intake and increase energy expenditure. This chapter discusses the role of serotonergic agonists, acting at 5-HT1 receptors, in the treatment of obesity secondary to mild depression. The stimulatory effect of benzodiazepines on food intake in animals has been known for some time, but this effect has not been demonstrated in humans. Moreover, benzodiazepine receptor antagonists do not suppress food intake. It was suggested that the decreased intake at higher doses might be because of locomotor depression. Decreased intake of palatable foods or a saccharin-glucose solution, but not a powdered diet, were seen. It also reversed the chlordiazepoxide-induced enhancement of palatability, suggesting that the effects of these partial benzodiazepine inverse agonists on food intake behavior are related to the palatability of foods. As observed in animals, mixtures of ephedrine, caffeine, and theophylline stimulate metabolic rate in humans to a greater extent than ephedrine alone. Measurement of 24-hour energy intake and expenditure indicate that individuals with a predisposition to obesity are more sensitive to the anorectic and thermogenic properties of the ephedrine/methylxanthine mixture than lean individuals. Clinical studies, comparing the activity of ephedrine to a mixture of ephedrine and methylxanthines, have not been discussed in the chapter.