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AICAR: What the Research Actually Shows

AICAR (5-aminoimidazole-4-carboxamide ribonucleoside, also called acadesine) is a small nucleoside that cells take up and convert into ZMP, which mimics AMP and activates AMP-activated protein kinase (AMPK). It has been used in laboratories since the 1990s as a tool for switching on AMPK in cells, and it was tested in people as a heart-surgery drug candidate that did not reach approval.

Below is what the studies looked at, in what kind of model, and what they reported. This is a summary of published research, not a description of what the compound does in a person.

Quick facts

• Names: AICAR, AICA riboside, acadesine (the international nonproprietary name). Code names in older trials include GP-1-110.
• What it is: a ribonucleoside, the building block of a nucleotide. It is not a peptide. Cells add a phosphate to it to make ZMP, a natural intermediate in purine synthesis.
• Molecular formula C9H14N4O5, 258.23 g/mol, CAS 2627-69-2 (PubChem CID 17513).
• Also made by the body: small amounts appear naturally in human urine (Thomas et al., 2010).
• Approval status: acadesine is not an approved drug in the United States, and the FDA‘s Drugs@FDA database lists no product containing it.
• Anti-doping status: the World Anti-Doping Agency’s 2026 Prohibited List names AICAR as an example of an AMPK activator in class S4.4, metabolic modulators, prohibited in and out of competition.

What the research found, and what it did not

Most of the studies below ran in cells or animals. The human studies are listed separately, and none of them tested AICAR on exercise or endurance. Results are listed as the authors reported them.

A tool for switching on AMPK (Corton, European Journal of Biochemistry, 1995). In rat liver cells, AICAR built up inside the cell as ZMP, which copied both of AMP’s activating effects on AMPK without changing the cell’s ATP, ADP or AMP levels. Fatty acid and sterol synthesis nearly stopped. The authors proposed it as a specific way to activate AMPK in intact cells, and posed that as a question in the title. Rat cells. PMID 7744080.

Fat cells (Sullivan, FEBS Letters, 1994). In isolated rat fat cells, AICAR activated AMPK and blunted both the breakdown of stored fat in response to a stimulating hormone and the building of new fat. Rat cells. PMID 7926017.

Muscle (Merrill, American Journal of Physiology, 1997). In rat muscle, AICAR raised AMPK activity, fatty acid oxidation and glucose uptake. Rat tissue. PMID 9435525.

The endurance study in mice (Narkar, Cell, 2008). The paper whose title called AICAR an exercise mimetic. Researchers gave AICAR to sedentary mice for 4 weeks and reported that it switched on muscle metabolic genes and raised treadmill running endurance without training. The same paper tested a PPARδ agonist, which raised endurance only when combined with training. Mice. PMID 18674809.

Effects that bypass AMPK (Višnjić, Cells, 2021). A systematic review of the field concluded that AICAR, though widely used as an AMPK activator, has important effects that do not depend on AMPK at all. That means a result seen with AICAR in a cell is not automatically an AMPK result. Review. PMID 34064363.

The human studies

Heart-surgery trials, pooled (Mangano, JAMA, 1997). Under the name acadesine, AICAR was tested in five randomized, placebo-controlled trials in patients having coronary bypass surgery. Pooled across 4,043 patients, the analysis reported fewer heart attacks and cardiac deaths around surgery in the acadesine groups, and a short-lived rise in blood uric acid. PMID 9002496.

The trial built to confirm it (Newman, JAMA, 2012). RED-CABG was a larger randomized, double-blind trial at 300 sites in 7 countries, designed to test acadesine in intermediate- to high-risk bypass patients. It was stopped early for futility after 3,080 of a planned 7,500 participants. The main outcome occurred in 5.1% on acadesine and 5.0% on placebo, so the trial found no benefit. PMID 22782417.

Muscle glucose uptake in healthy men (Cuthbertson, Diabetes, 2007). In 29 healthy men, an AICAR infusion roughly doubled muscle glucose uptake over 3 hours, against a near fivefold rise with cycling, and raised whole-body glucose disposal by 7%. AMPK activity and phosphorylation in muscle did not change with AICAR, while exercise raised them. A single infusion in a lab setting, not a training study. PMID 17513706.

Anti-doping history

AICAR moved from a lab tool to a sports-testing target after the 2008 mouse endurance study. Doping-control laboratories first classed its misuse under gene doping, and have since published methods for detecting it in urine (Thomas et al., 2010, Piper et al., 2014).

Today the WADA 2026 Prohibited List names AICAR in class S4.4, metabolic modulators, prohibited at all times. This page records that history as a fact about the compound.

How it works

AMPK is the cell’s fuel gauge. When energy runs low, AMP rises, AMPK switches on, and the cell shuts down energy-hungry building work (making fat and cholesterol) while turning up energy production (taking in glucose, burning fatty acids). Exercise is one of the strongest natural triggers of AMPK in muscle.

AICAR enters the cell and is converted to ZMP. ZMP looks enough like AMP to switch AMPK on, without the cell actually running low on energy (Corton, 1995). That is why it became a standard reagent.

Two limits sit on that picture. ZMP is also a step in purine synthesis, so AICAR touches more than AMPK, and a 2021 review catalogued many of those AMPK-independent effects (Višnjić, 2021). And in the one human muscle study, AICAR raised glucose uptake without a measurable rise in muscle AMPK activity (Cuthbertson, 2007).

Other compounds in this research area reach the same network from different points. MOTS-c is a mitochondrial peptide whose founding study also traced its effects to AMPK. SLU-PP-332 acts further down, at the ERR nuclear receptors.

What the research does not establish

• The endurance finding is from mice. No published human trial has tested AICAR on exercise capacity that we found.
• The human trials were in heart surgery, with the drug given by hospital staff around an operation. The larger, later trial found no benefit, and the compound was never approved.
• AICAR is not a clean AMPK switch. Many of its effects in cells do not depend on AMPK.
• Each finding describes what happened in a research model.
• Nothing here is a safety conclusion, and this is not a claim that the compound is safe to use.

Common questions

Is AICAR a peptide?

No. AICAR is a ribonucleoside, a sugar joined to a small ring-shaped base, with a molecular weight of about 258 (PubChem). It contains no amino acids. It shows up beside research peptides because it sits in the same AMPK and mitochondrial literature.

Is AICAR the same as acadesine?

Yes. Acadesine is the international nonproprietary name for AICAR, and it is the name used in the heart-surgery trials (Newman et al., 2012). AICA riboside is a third name for the same molecule.

Why is AICAR on the WADA prohibited list?

WADA names AICAR as an AMPK activator in its metabolic modulators class (2026 Prohibited List, S4.4). It became a doping-control target after a 2008 study reported longer running endurance in sedentary mice given AICAR (Narkar et al., 2008). WADA does not publish a reason per substance, so this answer describes the timeline, not WADA’s internal reasoning.

Has AICAR been tested in people?

Yes, but not for exercise. Under the name acadesine it was tested in randomized trials in heart-bypass surgery, and the largest trial was stopped early with no benefit found (Newman et al., 2012). A separate lab study in 29 healthy men measured muscle glucose uptake during a single infusion (Cuthbertson et al., 2007).

What is the difference between AICAR and MOTS-c?

AICAR is a nucleoside that switches on AMPK by imitating AMP (Corton et al., 1995). MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, and its founding study also linked its effects to AMPK, through a different route. AICAR has human trial data from surgery. MOTS-c research is mostly in cells and animals. No published study compares the two directly. See the MOTS-c research summary.

Does Etched Research sell AICAR?

No. Etched Research does not sell AICAR. This page is in the research library because the compound is part of mitochondrial and AMPK research, and the library covers more compounds than the shop does.

More in this research area: Cell Energy Research | Research Library

Last reviewed 2026-10-05.

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