Hexarelin

What Is Hexarelin?

Hexarelin is a synthetic hexapeptide (His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) and the most potent agonist in the growth hormone releasing peptide family. It binds the ghrelin receptor (GHS-R1a) in the hypothalamus and on pituitary somatotrophs, triggering a sharp pulse of endogenous growth hormone. The D-2-methyl-tryptophan at position 2 and D-phenylalanine at position 6 lock the molecule into a high-affinity conformation, giving roughly 30 times the GHS-R1a binding affinity of GHRP-6 and the largest GH pulse of any compound in the class. Combined with a GHRH analogue, it produces GH output exceeding the sum of either alone (the Bowers synergy effect).

Hexarelin also has a second, GH-independent mechanism that the more selective GHRPs lack. It binds the CD36 scavenger receptor on cardiomyocytes, activating PI3K/Akt signalling, upregulating heat shock proteins (HSP-70, HSP-90) and anti-apoptotic Bcl-2, and reducing mitochondrial cytochrome c release. This effect persists in GH-deficient animals. In rat heart-failure models, chronic hexarelin improved cardiac output by 28%, reduced left ventricular end-diastolic pressure by 34%, and cut cardiac fibrosis markers by 40 to 45%. The trade-offs are that hexarelin raises cortisol, prolactin, and ACTH alongside GH, and that GHS-R1a desensitises within 10 to 14 days of continuous exposure in the published studies.