Hexarelin

In this double-blind, placebo-controlled trial, healthy adult male volunteers received single intravenous boluses of hexarelin at 0.5, 1, and 2 micrograms/kg. Plasma growth hormone rose in a dose-dependent manner, peaking around 30 minutes post-injection and returning to baseline within 240 minutes, with peak concentrations ranging from about 3.9 to 55.0 ng/mL. Logistic regression estimated the half-maximal effective dose at roughly 0.5-0.64 micrograms/kg, indicating that the higher doses approached the maximal biological GH response.

In healthy men, a single injection of hexarelin caused a clear, dose-dependent spike in growth hormone that peaked at about half an hour and faded within four hours. Even relatively low doses produced strong GH release, and the largest doses came close to the maximum effect the drug can produce. This established hexarelin as a potent, short-acting stimulator of growth hormone in humans.

Using radioligand binding and protein purification from rat cardiac membranes, the authors identified an ~84 kDa hexarelin-binding protein as CD36, a multifunctional scavenger-receptor glycoprotein. In isolated perfused hearts, hexarelin acting via CD36 increased coronary perfusion pressure in a dose-dependent manner, and this vascular response was absent in CD36-deficient mice and rats. The findings define CD36 as a cardiac receptor distinct from the pituitary GHS-receptor and implicate it in the coronary vascular effects of growth hormone-releasing peptides.

Beyond releasing growth hormone, hexarelin acts directly on the heart by binding a protein called CD36 found on heart and blood-vessel cells. Experiments in hearts and in mice lacking CD36 showed that this protein is required for hexarelin's effects on coronary blood vessels. This identified a second, heart-specific target that explains why the peptide has cardiovascular activity independent of growth hormone.

In a mouse model of myocardial infarction, a single oral dose of hexarelin given 30 minutes after coronary ligation improved chronic cardiac function versus vehicle, yielding higher ejection fraction and fractional shortening and lower lung-weight ratios (indicating less pulmonary congestion). Treatment also lowered stress-hormone levels and shifted autonomic balance toward parasympathetic dominance. The authors concluded that a single oral hexarelin dose can protect long-term cardiac function after acute infarction, likely through growth hormone secretagogue receptor-mediated and related mechanisms.

In mice that had a heart attack, giving just one oral dose of hexarelin shortly afterward led to better heart pumping function weeks later and less fluid buildup in the lungs compared with untreated animals. It also calmed stress-hormone activity and tilted the nervous system toward a more restful state. This suggests hexarelin may have lasting protective effects on the heart even from a single early dose.