POTENTIAL ROLE OF NEUROPEPTIDE LIGANDS IN THE TREATMENT OF OVEREATING

This article reviews the role of various neuropeptides in controlling eating behaviour and the prospects for ligands of these signalling sys tems in the treatment of eating disorders, in particular overeating an d obesity. Neuropeptide Y is the most well known appetite-stimulating peptide. It is believed to exert this action through either Y-1 or Y-5 receptor subtypes in the hypothalamus. Selected antagonists with high affinity for these subtypes reduce food intake in animals, and so sug gest that the development of clinically useful analogues may be possib le. Galanin, another appetite-stimulating peptide, has been less well studied and the development of antagonists for galanin receptors is le ss well advanced. Studies using combinations of neuropeptide Y and gal anin receptor antagonists, that may target carbohydrate and fat intake , respectively, have not yet been reported. Several peptides are known to inhibit food intake. Agonists of receptors for these peptides that have a long duration of action could be useful appetite suppressants. These peptides include 'gut' peptides such as cholecystokinin and glu cagon-like peptide, and 'pancreatic' peptides such as amylin and insul in. Recently, the obesity (ob/ob) gene-related peptide leptin has been proposed as an endogenous signalling system that regulates fat intake , and a novel analogue of leptin has been shown to reduce food intake in rats. These peptides are thought to act on feeding-related regions at various levels of the neuraxis, prominently including the nucleus o f the solitary tract, the lateral parabrachial nucleus, the paraventri cular hypothalamus and the amygdala.