Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs

Ghrelin is a hormone, secreted from cells in the stomach, which is important in the regulation of appetite and food intake in mammals. It exerts its action by binding to a specific G-protein-coupled receptor, the growth hormone secretagogue receptor 1a (GHS-R1a) which is found in areas of the brain associated with the regulation of food intake. Ghrelin causes a release of growth hormone (GH) through binding to GHS-R1a in the hypothalamus and pituitary gland. A class of compounds known as growth hormone secretagogues, or ghrelin receptor agonists, were developed for therapeutic use in humans for the stimulation of GH in the frail elderly, and have subsequently been studied for their effects on increasing appetite and food intake, increasing body weight, building lean muscle mass, and treating cachexia. Subsequent research has shown that ghrelin has anti-inflammatory and immunomodulatory effects. This article reviews the basic physiology of ghrelin and the ghrelin receptor agonists, including the available evidence of these effects in vitro and in vivo in rodent models, humans, dogs and cats. One of these compounds, capromorelin, has been FDA-approved for the stimulation of appetite in dogs (ENTYCE ®). The data available on the safety and effectiveness of capromorelin is reviewed, along with a discussion of the potential clinical applications for ghrelin receptor agonists in both human and veterinary medicine.