Examorelin / Hexarelin
(His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2)

Act One: The Quest for a Better Growth Hormone Drug

Building a Better Messenger

How a chemical modification created the world's strongest growth hormone peptide

In the 1980s, growth hormone was revolutionizing medicine. Doctors used it to help kids grow taller, to heal wounds faster, to build muscle in sick patients. But there was a problem: growth hormone had to be injected directly into the bloodstream every day, and it was expensive. Scientists asked a simple question: what if we could make the body produce its own growth hormone? What if we could trick the brain's pituitary gland into making more? In 1984, an American researcher named Bowers created GHRP-6, the first peptide that could do this. It worked—but it was weak and didn't last long in the bloodstream.

Enter Romano Deghenghi, a brilliant Italian peptide chemist at Mediolanum Farmaceutici in Milan. Deghenghi studied GHRP-6 and saw its weaknesses. He asked himself: what if I changed just one amino acid? What if I replaced the tryptophan at position 2 with a special D-form of 2-methyl-tryptophan? In 1992, he synthesized hexarelin. The results astonished everyone. Hexarelin was roughly 10 times stronger than GHRP-6. It lasted longer. It was more stable. It worked better.

The name itself tells the story. 'Hex' means six, and this peptide has six amino acids: His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys. Call it a chemical haiku—incredibly short, incredibly powerful. Deghenghi published his findings and other researchers rushed to confirm his work. Every lab that tested hexarelin got the same result: this peptide was special.

What made Deghenghi's modification so clever? Think of a key fitting into a lock. GHRP-6's tryptophan was a decent key. But Deghenghi's 2-methyl-tryptophan was a better key—it fit more snugly into the sensor on the pituitary cell that receives the message. The modified tryptophan also resisted being broken down by the stomach and liver. A stronger grip plus longer survival equals a better medicine.

By 1994, Deghenghi's creation was ready for human testing. Other scientists around the world wanted to study it. Ezio Ghigo at the University of Turin volunteered to lead the first human trials. Nobody knew then that hexarelin's greatest strength had nothing to do with growing taller. The real story was about to begin.

Act Two: The Four Routes—A Peptide Like No Other

Peptide That Works Everywhere

Proving that hexarelin could be swallowed, sprayed, or injected—breaking the peptide rules

By 1994, peptides had a reputation. They were fragile. They couldn't survive the stomach. They couldn't cross membranes. If you wanted to use a peptide, you had to inject it. Scientists accepted this as fact. Peptides were prisoners of the needle.

Hexarelin shattered this assumption. Ezio Ghigo and his team in Turin tested four different delivery methods in human volunteers. They injected it into a vein (IV). They injected it under the skin (subcutaneous). They sprayed it up volunteers' noses (intranasal). They had volunteers swallow it (oral). Then they measured how much of the peptide actually reached the bloodstream—what scientists call bioavailability.

The results were revolutionary. Intravenous injection, as expected, showed 100 percent bioavailability—all of it got into the blood. Subcutaneous injection showed 77 percent bioavailability—still excellent. Intranasal delivery showed 4.8 percent bioavailability. And oral delivery showed 0.3 percent bioavailability. Wait—0.3 percent doesn't sound good. But here's the trick: 0.3 percent of a massively potent peptide is still enough to work. It was like discovering you could power a city with just a spark from a bonfire.

This meant something profound. For the first time, a growth hormone peptide could reach patients multiple ways. Doctors could inject it for fast action. They could spray it up the nose for easier use. They could even give it as a pill, though the effect was weaker. Older peptides couldn't do this. Hexarelin was designed like a lock-and-key system that worked from four different directions.

Zvi Laron in Tel Aviv decided to test intranasal hexarelin in short children. He sprayed the peptide up their noses three times a day. Within weeks, their growth accelerated. Here was a growth hormone peptide that worked without needles, without pain, without injections. Parents loved it. Children didn't fear it. Laron's work proved that this wasn't just laboratory elegance—it was practical medicine.

But the real significance of the four routes wasn't about delivering growth hormone more conveniently. It was that scientists now had flexible tools to test hexarelin's effects in real human brains, hearts, and tissues. They could learn things impossible with peptides that only worked one way. This flexibility became crucial when hexarelin's secret was about to be revealed.

Act Three: The Shocking Discovery—A Heart Drug Hiding in a Growth Hormone Peptide

When Growth Becomes Healing

How scientists discovered hexarelin protects failing hearts—without growth hormone

In 2000, something unexpected happened in a Swedish laboratory. Researchers including Anders Tivesten studied rats that had suffered a heart attack by having their coronary artery tied shut. They treated half the rats with hexarelin and half with a placebo. Six weeks later, they measured the rats' hearts. The hexarelin-treated rats had significantly better heart pumping strength. Their hearts recovered better. Their damaged tissue wasn't as scarred. This wasn't shocking by itself—growth hormone was known to help hearts—but then came the surprise.

The researchers gave hexarelin to rats with no pituitary glands. These rats had zero growth hormone. They couldn't make any. Yet their hearts still improved after heart attacks. The cardiac protection didn't depend on growth hormone at all. This was the moment everything changed. Hexarelin wasn't just a growth hormone delivery system. It was something new: a direct heart medicine.

In 2002, Massimo Imazio at the University of Turin decided to test this in human heart failure patients. He gave intravenous hexarelin to patients with severely weakened hearts. Some had ischemic cardiomyopathy—hearts damaged by heart attacks. Others had dilated cardiomyopathy—hearts stretched thin and weak. In the ischemic group, something remarkable happened. The left ventricle ejection fraction, a key measure of pumping strength, improved from about 22 percent to 26 percent. That 4-point jump might sound small, but in cardiology it's huge. It meant hexarelin strengthened the heart's contractions.

Think of the heart as a pump with a clenched fist. When the fist squeezes, blood goes out. When it relaxes, blood comes back in. In ischemic cardiomyopathy patients, the fist was barely clenching—only 22 percent maximum force. After hexarelin, it clenched 26 percent. That percentage point difference could mean the difference between life and death for someone in heart failure. In the dilated cardiomyopathy patients, hexarelin didn't help as much, but it didn't hurt. The point was: it worked.

Over the next two decades, researchers discovered how hexarelin protected hearts. It reduced inflammation. It stopped heart cells from dying. It decreased scar tissue formation. It changed the balance of the nervous system, shifting it from fight-or-flight to rest-and-digest mode. It did all of this through direct effects on heart cells, not through growth hormone. Scientists found the sensor that hexarelin activates—something called the ghrelin receptor. Heart cells have these sensors. When hexarelin sticks to them, it tells heart cells to heal, to survive, to pump harder.

This was the drug that nobody expected. Nobody designed hexarelin thinking, 'I will create a heart medication.' Deghenghi designed a growth hormone peptide. But nature gave it a bonus power. It was like discovering your car could also fly—a completely unexpected capability.

Act Four: The Forgotten Molecule—Why a Miracle Drug Disappeared

The Mystery of Abandonment

A peptide that showed promise for two life-threatening diseases, then vanished

By the year 2000, hexarelin had done something remarkable. It worked in multiple countries. It worked in multiple patient groups. It showed potential for growth hormone deficiency. It showed potential for congestive heart failure. It had a safety profile that seemed acceptable. Hundreds of scientific papers proved its effects. The Foundation for Research and Development of Hexapeptides had been created. Clinical trials were ongoing. Everything pointed to approval and commercial success.

Then, mysteriously, Mediolanum Farmaceutici stopped developing hexarelin. The company gave a vague statement: 'strategic reasons.' They didn't explain. They didn't announce a new direction. The pharmaceutical company simply walked away from a molecule that showed promise for two diseases that kill millions of people. Hexarelin reached Phase II trials—the middle stage where researchers confirm that a drug works and is safe enough to expand testing. But Phase II was where the journey ended.

Why would a company abandon a breakthrough drug? Nobody knows for certain. Some experts guess that heart failure treatment was more complex than the company expected. Some suggest the peptide's cost to manufacture was too high. Some wonder if the company's business strategy changed. Some propose that proving benefit to shareholders wasn't clear enough. Whatever the reason, Mediolanum Farmaceutici made a business decision that meant millions of heart failure patients never had access to hexarelin. People who might have lived longer, who might have suffered less, never got the chance.

But here's the strange thing: the research didn't stop. Scientists kept studying hexarelin. They kept publishing results. They kept discovering new things about how it works. Over the next two decades, research groups in Australia, China, South Korea, and Europe continued the work. They showed that hexarelin reduced fibrosis—the scarring that stiffens failing hearts. They showed it preserved the structure of heart tissue. They showed it calmed the overactive nervous system of heart failure patients. They showed it protected heart cells from dying. With each study, the evidence grew stronger. With each discovery, it became clearer that Mediolanum had walked away from something important.

In 2018 and beyond, researchers at Australian institutions published striking new evidence. One dose of oral hexarelin, given immediately after a heart attack in mice, protected the heart for months afterward. Chronic heart function stayed better. Scarring was reduced. The effect was so clear that researchers called it a major discovery. Yet outside the scientific community, almost nobody knew about it. Hexarelin had become a ghost drug—alive in laboratories, dead in clinics.

Act Five: The Resurrection—Why Scientists Won't Let Hexarelin Die

Second Chances for Forgotten Medicines

How modern researchers are reviving a 30-year-old peptide for a new era

The story doesn't end in 2006. It changes direction. If Mediolanum Farmaceutici had abandoned hexarelin, the scientific community had not. Research groups around the world kept publishing. In 2014, Tokudome and colleagues in Japan showed that a single oral dose of hexarelin protected chronic heart function in a mouse heart attack model. Imagine: one pill, one time, given right after a heart attack, and the protection lasted months. It was like getting a vaccine against heart damage. In 2018, McDonald and team at Australian universities published stunning results. Not only did hexarelin preserve heart function, it specifically reduced cardiac fibrosis—the scarring process that kills heart failure patients.

Why is Australia so interested in hexarelin? Because heart disease is a massive problem. Millions of people develop failing hearts from heart attacks, infections, high blood pressure, or diabetes. Current treatments help but don't cure. Doctors give ACE inhibitors, beta-blockers, diuretics, and expensive injectable proteins. All help, but all leave patients with weakened hearts. A new option, especially one as proven as hexarelin, could change lives. Australian cardiologists decided that just because Mediolanum walked away didn't mean hexarelin deserved to stay forgotten.

In 2019, Agbo and Liu showed that hexarelin's benefits come from changing something called PTEN. In 2020, researchers showed that hexarelin targets 'neuroinflammatory pathways'—the ways that inflammation in the nervous system damages the heart. In 2021, advanced imaging studies by Waddingham and team used synchrotron radiation to visualize exactly what hexarelin does at the cellular level in heart tissue. Each study answered questions. Each study opened new ones. The puzzle was becoming clearer.

Today, nobody is developing hexarelin commercially. No pharmaceutical company is pursuing FDA approval. The molecule remains available only for research. But that's changing. There's growing interest from researchers who remember hexarelin's promise and new researchers who are discovering it for the first time. Some labs are studying how to improve hexarelin's design—what if we modified it slightly to make it even more effective? What if we combined it with other heart medicines? What if we delivered it in new ways? Others are asking regulatory questions: could we use existing safety data to move faster to clinical trials? What would it take to revive hexarelin in the era of modern medicine?

Maybe the story of examorelin isn't about failure. Maybe it's about a molecule that outlived its corporate sponsors. A peptide so robust, so effective, so important that scientists wouldn't let it disappear. In laboratories from Australia to China to Europe, hexarelin lives on. And in the hearts of researchers who believe that sometimes the best medicines come from the past, there is hope that hexarelin's second act is just beginning.