Tesamorelin + Ipamorelin (Blend)

The GHRH receptor, the target of Tesamorelin, is coupled to the Gs protein and works by raising cyclic AMP inside the somatotroph, which drives both the release of stored growth hormone and the production of new hormone. The GHSR, the target of Ipamorelin, is coupled mainly to Gq and works through phospholipase C and a rise in intracellular calcium. The GHSR is also found in the hypothalamus, where ghrelin-receptor agonists appear to weaken the restraining effect of somatostatin. Because the two signals travel by different routes, a pituitary cell receiving both can respond more strongly than to either one alone.

That cooperation has been measured directly with the body’s own ghrelin. In 2001, Hataya and colleagues at Kyoto University gave healthy men GHRH alone, ghrelin alone or the two together, and found that at low ghrelin doses the combined GH response was greater than the two single responses added together. There was no matching synergy in ACTH or prolactin (Learn more). A blend of a GHRH analogue with a ghrelin-receptor agonist is a practical way to model that interaction in the laboratory.

The ghrelin route was discovered backwards. Synthetic growth-hormone-releasing peptides such as GHRP-6 were in laboratory use through the 1980s, long before anyone knew what they acted on. In 1996, a Merck team led by Howard cloned their target, a G-protein-coupled receptor in the pituitary and hypothalamus (Learn more), and suggested that the body must make a hormone of its own for it. Three years later, Kojima and colleagues isolated that hormone from rat stomach and named it ghrelin. Ipamorelin, published in 1998, was designed in the gap between those two discoveries.

Natural GHRH is 44 amino acids long and is broken down quickly in the blood, mainly by the enzyme dipeptidyl peptidase IV, which cuts between the second and third residues. Tesamorelin keeps the whole human sequence and adds a trans-3-hexenoyl group at the point where that enzyme attacks. That makes it different from Sermorelin and Mod GRF 1-29, which use only the first 29 residues, and from CJC-1295 with DAC, which is built to bind albumin and last for days.

Tesamorelin also has one of the largest human datasets of any GHRH analogue. In a 26-week trial of 412 adults with HIV-associated abdominal fat, published in the New England Journal of Medicine in 2007, visceral fat measured by CT fell by 15.2% on Tesamorelin and rose by 5.0% on placebo, while IGF-1 rose by 81% (Learn more). That work led to its US approval as Egrifta in 2010 for that single, narrow use. Crown Peptides supplies a lyophilised research material, not the branded medicine; our Tesamorelin page covers its liver and cognitive research in detail.

By weight, the vial holds more than three times as much Tesamorelin as Ipamorelin. By number of molecules, the balance is the other way round. Tesamorelin weighs about 5,136 g/mol and Ipamorelin about 712 g/mol, so 10mg of Tesamorelin is roughly 1.95 micromoles while 3mg of Ipamorelin is roughly 4.21 micromoles. Each vial therefore contains a little over two Ipamorelin molecules for every Tesamorelin molecule. That is worth bearing in mind when comparing results with studies that report their combinations in molar terms.

The size gap also helps with analysis. On HPLC the two peptides interact with the column differently and come off at different times, giving two distinct peaks, and on mass spectrometry their masses are around seven times apart, so each identity can be confirmed from one sample of the mixture.