An approach to the development of drugs for appetite disorders

This review covers some modern concepts in the development of drugs to treat appetite disorders. Specific attention is paid to the peripheral satiety system and the role of gastrointestinal peptides such as cholecystokinin in the pathogenesis of satiety. Alterations in neuropeptide Y and/or peptide YY are suggested to play a role in the pathophysiology of bulimia. Corticotropin-releasing factor is a putative candidate peptide involved in anorexia nervosa. The serotonin reuptake inhibitors fenfluramine and fluoxetene decrease weight in obese subjects. Endogenous opioids modulate the choice of palatable foods. Anorexia in the old appears to be related to a decrease in opioid feeding drive and an excess of the satiety action of cholecystokinin. Other agents involved in weight regulation include those which alter gastric emptying, increase thermogenesis, or modulate fat cell metabolism. It should be stressed that many neurotransmitters that modulate appetite also alter other behaviors, increasing their propensity to produce side effects.