Relamorelin

Relamorelin, also known by its development code RM-131, is a synthetic pentapeptide agonist of the ghrelin receptor. Ghrelin, a 28-amino-acid acylated hormone discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor, is produced mainly by the stomach and influences appetite, growth hormone release and gastrointestinal motility. Relamorelin was designed to be considerably more potent and more stable than native ghrelin, which depends on a fragile octanoyl modification for activity.

Relamorelin was developed by Rhythm Pharmaceuticals and later licensed to Allergan, with research focused on diabetic gastroparesis, a condition of delayed gastric emptying without mechanical obstruction. Phase 2 studies reported accelerated gastric emptying, and phase 3 trials were completed, but the compound has not been approved by the FDA or EMA. It also features on the WADA prohibited list as a growth hormone secretagogue. For researchers, relamorelin is a useful probe of how ghrelin receptor signalling influences gastric motor function, and it illustrates the difficulty of translating improvements in gastric emptying measures into consistent symptom endpoints.

Relamorelin binds and activates the growth hormone secretagogue receptor type 1a, GHS-R1a, a GPCR expressed in the pituitary, hypothalamus and along the vagal and enteric nervous systems. In the gut, ghrelin receptor activation stimulates gastric antral contractions and promotes the migrating motor complex, accelerating gastric emptying in experimental and clinical studies. Effects are thought to involve both vagal pathways and direct actions on enteric neurons. At the pituitary, GHS-R1a activation stimulates growth hormone release, and hypothalamic activation influences appetite. Relamorelin's peptide modifications increase receptor potency and plasma stability compared with acylated ghrelin.