AICAR

Origin and structure

AICAR is not a peptide and contains no amino acids. It is a nucleoside: a small imidazole ring carrying an amino group and a carboxamide group, attached to the sugar ribose. Inside cells it picks up a phosphate group and becomes ZMP, which is also a normal intermediate in the body's own production of purines, the building blocks of DNA, RNA and ATP. Small amounts of AICAR are therefore always present in the body and in urine.

The name causes confusion. In biochemistry 'AICAR' has long been used for the ribotide, ZMP, the form with the phosphate attached. In AMPK research, in doping control and in trade, 'AICAR' means the riboside, the form that can enter cells; some researchers write AICAr to keep the two apart. As a drug candidate the riboside is called acadesine.

As a medicine it was developed by Gensia Pharmaceuticals in San Diego as an 'adenosine-regulating agent', meant to limit the damage to heart muscle when blood flow returns after a period without oxygen. It was tested in five randomised trials of heart bypass surgery at 81 centres in the United States, Canada and Europe, pooled in a 1997 analysis, and in a final phase 3 trial that ran from 2009 to 2010. The Spanish company Advancell later took it into early trials in leukaemia. Separately, after a 1995 study showed that it switches on AMPK in intact cells, it became a standard laboratory tool in metabolism research, and a 2008 mouse study made it famous as an 'exercise mimetic'.

How it is thought to work

Once inside a cell, AICAR is turned into ZMP, which mimics AMP. AMP builds up when a cell runs short of energy and switches on AMPK, an enzyme that then turns energy-consuming processes down and energy-producing ones up. In a 1995 study in rat liver cells, ZMP copied both ways in which AMP activates AMPK, without changing the cells' own levels of ATP, ADP or AMP, and the production of fat and cholesterol almost stopped. That made AICAR the usual way to switch on AMPK in laboratory experiments.

Whether this is how it acts in people is less clear. In Scottish studies, infusions raised glucose uptake into thigh muscle, but the researchers could not detect any increase in AMPK activity in the muscle; the uptake tracked a different signalling enzyme, ERK1/2. So not every effect of AICAR can be assumed to run through AMPK. In the heart trials it was presented differently again, as an agent that regulates adenosine in heart muscle short of oxygen.

In healthy men an intravenous dose was cleared quickly, with a half-life of about 1.4 hours, and red blood cells took it up and turned it into ZMP. Given by mouth as a solution, less than 5% reached the bloodstream. It is broken down along the body's purine pathway, and in patients it raised uric acid, the end product of that pathway.

Is AICAR approved?

No. No medicine containing AICAR or acadesine has a marketing authorisation in the EU, the Netherlands or the US; it has only ever been an investigational drug.

Research-grade AICAR is not a medicine either. It has no marketing authorisation, is not made under a medicines licence and may not be used in people.

• EU: the European Commission gave acadesine two orphan designations, both held by the Spanish company Advancell: for B-cell chronic lymphocytic leukaemia on 27 May 2005 and for multiple myeloma in August 2011. Both are still listed in the EU register. An orphan designation gives a company incentives to develop a medicine for a rare disease; it is granted before the medicine has been shown to work and is not an authorisation.
• Netherlands: no medicine with AICAR or acadesine is listed in the Dutch medicines register (Geneesmiddeleninformatiebank), so it cannot be prescribed as a licensed medicine.
• US: the FDA has never approved acadesine. Its last trial in heart surgery, the phase 3 RED-CABG study, was stopped in 2010 after a planned interim analysis showed it was very unlikely to succeed.

What the research shows

Nearly all controlled human data come from heart surgery, where acadesine was given as an infusion in hospital. The studies of metabolism in people are small and lasted hours, the leukaemia trials were early-phase, and the endurance claims rest on mice:

• Heart bypass surgery, first five trials: five randomised placebo-controlled trials with 4,043 evaluable patients. In a pooled analysis of the individual patient data (JAMA 1997), acadesine lowered the rate of heart attack around the operation by 27% (odds ratio 0.69, 95% CI 0.51 to 0.95) and cardiac death in the first four days by about half (odds ratio 0.52); stroke was not significantly reduced.
• RED-CABG (JAMA 2012): the phase 3 trial meant to confirm this, in intermediate- to high-risk patients at 300 sites in seven countries. It was stopped after 3,080 of a planned 7,500 patients because a prespecified futility analysis showed almost no chance of success: death, non-fatal stroke or severe heart failure needing mechanical support occurred in 5.1% on acadesine and 5.0% on placebo (odds ratio 1.01, 95% CI 0.73 to 1.41). Key secondary outcomes did not differ either.
• Muscle glucose uptake (Scotland, 2009): at the lower dose, a three-hour infusion raised glucose uptake into thigh muscle 2.9-fold in six healthy young men, 1.8-fold in eight older men and 1.6-fold in eight men with type 2 diabetes; the higher dose raised it 2.5-fold and 2.2-fold in the two older groups. Muscle AMPK activity did not rise measurably. The authors concluded that the smaller response depended on age rather than on diabetes. An earlier study by the same group in young men had also found no rise in muscle AMPK activity.
• Type 2 diabetes (Maastricht, 2008): in ten men with type 2 diabetes, a single infusion lowered the output of glucose by the liver, blood glucose and blood fatty acids, again without a rise in AMPK phosphorylation in muscle. No trial has tested repeated doses for diabetes.
• Leukaemia: in a phase 1/2 trial in 24 patients with relapsed or refractory chronic lymphocytic leukaemia (2013), four-hour infusions gave signs of fewer leukaemia cells in the blood and smaller lymph nodes, but the results varied too much to judge in so few patients and across so many doses. A French phase 1/2 trial in myelodysplastic syndrome and acute myeloid leukaemia was stopped because the highest dose caused serious kidney side effects in several patients (reported in 2019). No later-phase trial is registered.
• Endurance in mice (Cell 2008): four weeks of daily AICAR injections in sedentary mice switched on genes for oxidative energy metabolism in muscle and let them run about 23% longer and 44% further on a treadmill than untreated mice. This has never been tested in people.

Side effects and warnings

In the heart-surgery trials, where patients received a single seven-hour infusion, adverse events were about as common on acadesine as on placebo, apart from a temporary rise in uric acid in the blood. In healthy men in the first dosing study, side effects were mild and short-lived and were also reported on placebo.

The much higher doses of the leukaemia trials caused more problems. In the trial in chronic lymphocytic leukaemia a raised uric acid level was common but not clinically significant, and resolved with preventive use of the gout medicine allopurinol; the clinically significant side effects were impaired kidney function and a temporary drop in blood pressure during the infusion, and some patients had temporary anaemia or low platelet counts. The French trial in myelodysplastic syndrome was stopped over serious kidney side effects.

All of these data come from single or a few intravenous infusions under medical supervision. There are no human data on repeated injections under the skin or on use over weeks or months, the way AICAR is discussed online, and no long-term safety data at all.

AICAR in sport and doping control

AICAR is prohibited at all times, in and out of competition. WADA names it in class S4.4.1 of the Prohibited List, activators of AMPK, together with MOTS-c and BAM15, and the 2027 List, which takes effect on 1 January 2027, keeps it there. In the Netherlands the Dopingautoriteit applies the same list.

Because the body makes AICAR itself, a test cannot simply look for its presence. Doping laboratories flag urine with unusually high levels and then measure the ratio of carbon isotopes in the AICAR, which tells AICAR made in the body apart from AICAR from outside it. In the 2014 study that validated this test, a single oral dose could be detected for more than 40 hours.

Frequently asked questions

Is AICAR a peptide?

No. AICAR is a nucleoside, a sugar-bound molecule related to the purines in DNA and ATP, and it contains no amino acids. It turns up next to peptides because it is sold and discussed alongside them, and because WADA lists it in the same class as the mitochondrial peptide MOTS-c, the activators of AMPK.

Is AICAR legal in the Netherlands?

No medicine containing AICAR or acadesine is authorised in the Netherlands or elsewhere in the EU, so a doctor cannot prescribe it as a licensed medicine. Research-grade AICAR is laboratory material, not a medicine, and may not be used in people. In sport it is prohibited at all times.

Is AICAR banned in sport?

Yes, at all times, in and out of competition. WADA names AICAR in class S4.4.1 (activators of AMPK) of the 2026 Prohibited List and keeps it there in the 2027 List; the Dopingautoriteit applies the same list in the Netherlands. Because the body makes small amounts itself, laboratories confirm suspicious samples with a carbon isotope test that tells AICAR from outside the body apart from the body's own.

Does AICAR work as 'exercise in a pill' in humans?

That has never been shown. The idea comes from a 2008 study in which sedentary mice given daily injections for four weeks ran 44% further. In people, single three-hour infusions raised glucose uptake into muscle without measurable AMPK activation in the muscle, and no trial has tested endurance, muscle mass or fat loss. By mouth, less than 5% of a dose is absorbed.

What is the difference between AICAR, acadesine and ZMP?

AICAR as used in AMPK research and doping control and acadesine are the same molecule, the riboside; acadesine is its name as a drug candidate. ZMP is what cells make from it by adding a phosphate group, and it is the form that activates AMPK. In older biochemistry 'AICAR' can also mean ZMP, which is why some papers write AICAr for the riboside.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.