Every cell monitors its own energy supply through an enzyme called AMPK. AICAR is the compound laboratories have used for thirty years to switch that enzyme on and watch what changes.
AICAR · AMPK-activating nucleoside (literature compound)
Cells keep track of how much energy they have. When supply runs low, an enzyme called AMPK is activated and shifts the cell towards burning fuel and away from building and storing. Researchers ask what happens when that switch is thrown deliberately, and AICAR, meaning acadesine in the studies discussed here, is the standard tool for doing so. Evidence is mostly from cells and rodents, plus older human trials of the same molecule in heart surgery.
AICAR, in the sense the research literature uses the name, is 5-aminoimidazole-4-carboxamide ribonucleoside, also called acadesine: a small molecule made of a ring structure joined to a sugar, resembling the building blocks of DNA and RNA. It is not itself a peptide.
The distinction that matters is what happens inside the cell. Cells take up the ribonucleoside and add a phosphate group to it, producing ZMP, the ribonucleotide. ZMP is a natural intermediate in the pathway that makes purines, and it resembles AMP, the low-energy signal that cells produce when fuel is short. Because of that resemblance, ZMP activates AMPK, AMP-activated protein kinase, without changing the cell's real ATP, ADP or AMP levels. That sequence, ribonucleoside in, ZMP formed, AMPK switched on, was established in rat liver cells (Corton et al., 1995) and in perfused rat muscle (Merrill et al., 1997). The material that enters the cell and the molecule that does the signalling are different chemicals.
In the studies discussed here, AICAR refers to acadesine, a ribonucleoside converted inside cells to ZMP. The chemical identity of the supplied material has not yet been confirmed against a supplier specification, so this research summary does not establish which form this listing contains.
In perfused rat hindlimb muscle, AICAR activated AMPK, inactivated the enzyme acetyl-CoA carboxylase, lowered malonyl-CoA and increased fatty-acid oxidation and glucose uptake, the pattern later used to define AMPK's metabolic role (Merrill et al., 1997).
In 2008 a Salk Institute group reported that four weeks of daily AICAR injections increased running endurance in untrained mice, with changes in the genes that shift muscle towards oxidative metabolism (Narkar et al., 2008). That mouse result is the origin of the 'exercise mimetic' label; it describes gene programmes in rodents, not a substitute for exercise in people.
The same molecule was tested in people under the name acadesine, given intravenously to protect the heart during coronary artery bypass surgery. RED-CABG, a randomised trial in 3,080 patients, was stopped for futility: acadesine did not reduce death, stroke or heart attack compared with placebo (Newman et al., 2012). A 2021 systematic review catalogued the many cell and animal effects of AICAR that turned out not to depend on AMPK at all (Visnjic et al., 2021).
AICAR is not a clean switch. Because ZMP also feeds purine synthesis and affects other enzymes, many reported effects cannot be attributed to AMPK, which limits what any single AICAR experiment proves. Uptake and conversion to ZMP vary between tissues, so cell-culture concentrations do not translate to whole animals, and rodent endurance findings have no human counterpart.
The human trials were of intravenous acadesine during surgery, a different question from metabolism, and they were negative. The compound has not been approved as a medicine.
AICAR (acadesine) is not an approved medicine in Australia, and no approval elsewhere was identified; its clinical development for cardiac surgery ended after the RED-CABG trial. It is named on the WADA 2026 Prohibited List under S4.4.1, metabolic modulators (AMPK activators), and is prohibited at all times in sport.
Sources and status checked 2026-09-22
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