Hexarelin

What it is

Hexarelin (His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide analogue of GHRP-6 with enhanced potency. At 887.1 g/mol, it is a compact but highly active peptide. What makes Hexarelin particularly interesting from a research perspective is its dual receptor binding: it activates both the GHS-R1a (ghrelin) receptor — the basis for its GH-releasing effects — and the CD36 receptor, a scavenger receptor expressed in cardiac tissue. This CD36 binding is the basis for its separately investigated cardioprotective effects, which appear to be at least partially independent of GH release.

How it works

At the pituitary, Hexarelin stimulates GH release via GHS-R1a binding — more potently than most other synthetic GHRPs. However, unlike Ipamorelin, it is not selective: it also stimulates ACTH and cortisol release at research concentrations, as well as prolactin. At the cardiac level, Hexarelin's CD36 binding has been studied in models of cardiac ischaemia, where it appears to protect cardiomyocytes from apoptosis, reduce infarct size, and attenuate the decline in cardiac contractile function following ischaemic injury. Crucially, research has shown these cardioprotective effects can persist even when GH receptor signalling is blocked, suggesting a direct cardiac mechanism independent of GH.

Research context

Research on Hexarelin spans GH axis studies, cardiac protection models, and investigation of its unique CD36 receptor interactions. Landmark studies by Bisi et al. demonstrated dose-dependent GH release in human subjects. Separately, Bodart et al. published influential work establishing CD36 as the mediator of Hexarelin's cardioprotective effects — demonstrating that these effects were retained in GH-deficient animals and blocked by CD36 antagonism. This dual mechanism makes Hexarelin one of the most mechanistically interesting compounds in the GHRP class.