Current Drug Targets

Author(s): Jason C.G. Halford, Gillian D. Cooper and Terence M. Dovey

DOI: 10.2174/1389450043490541

The Pharmacology of Human Appetite Expression

Page: [221 - 240] Pages: 20

  • * (Excluding Mailing and Handling)

Abstract

The discovery of the adiposity signal leptin a decade ago revolutionised our understanding of the hypothalamic mechanisms underpinning the central control of ingestive behaviour. Subsequently, the structure and function of various hypothalamic peptide systems (Neuropeptide Y (NPY), Orexins, Melanocortins, Cocaine and Amphetamine Regulating Transcript (CART), Galanin / Galanin Like Peptides (GALP) and endocannabinoids) have been characterised in detail in rodent models. The therapeutic benefit of targeting these systems remains to be discovered. More is becoming known about the pharmacological potential of peripheral, meal-induced, episodic endogenous peptides. Hormones such as Cholecystokinin (CCK), Gastrin Releasing Peptides (GRP), Glucagon- Like Peptide 1 (GLP-1) Enterostatin, Amylin, Peptide YY (PYY) and Ghrelin are released prior to, during and / or after a meal, controlling intake and subjective feelings of appetite (hunger and satiety). In addition, there is an expanding body of literature detailing the effects of a wide variety of drugs on human appetite and food intake. Some of these drugs act upon CNS monoamine systems such as Serotonin (5-HT), Dopamine (DA) and Noradrenaline (NA), have long been implicated in appetite regulation. Detailed examination of both the effect of agonising endogenous gut peptide systems and the effect of various monoaminergic drugs on the expression of human appetite can provide a greater understanding of mechanisms underpinning normal appetite regulation. However, such an understanding must be based on knowledge of the effect of the treatment on meal size, eating rate, meal pattern, food choice and the subjective experience of appetite flux (hunger and satiety), and not just food intake.

Keywords: human appetite, food intake, meal, satiety, hunger, drugs, monoamines, gut peptides