Skeletal-muscle endurance in sedentary mice — preclinical
in vivoNarkar 2008: 4 weeks of daily AICAR injection in sedentary mice increased run-time-to-exhaustion by ~44 % without training.
— Narkar VA et al. 2008, Cell 134(3):405-415
AMPK activator / purine nucleoside (exercise-mimetic research) Limited Human Data
AICAR
Also Known As: Acadesine, AICA Riboside, 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, GP-531
AICAR (5-aminoimidazole-4-carboxamide riboside, INN acadesine) is a purine nucleoside analogue that is phosphorylated intracellularly to AICA ribotide (ZMP), which allosterically activates AMP-activated protein kinase (AMPK) by mimicking AMP. It is NOT a peptide; it is listed alongside the research peptides for operational reasons. Made famous by the 2008 Narkar study framing AICAR as "exercise in a pill" for skeletal-muscle adaptation in mice. Limited human data — research use only; WADA-prohibited.
Mechanism of Action
Studies report that AICAR is phosphorylated intracellularly to ZMP, which allosterically activates AMPK by mimicking AMP and stimulates mitochondrial biogenesis and fatty-acid oxidation. Observed in research settings.
AICAR is an adenosine analogue; after cellular uptake it is phosphorylated by adenosine kinase to AICA ribotide (ZMP). ZMP mimics AMP and allosterically activates AMPK without changing the cellular AMP pool. Activated AMPK phosphorylates acetyl-CoA carboxylase (ACC, inhibiting fatty-acid synthesis), HMG-CoA reductase, and TSC2 (inhibiting mTORC1), and drives transcriptional upregulation of PGC-1α-mediated mitochondrial biogenesis. Narkar 2008 reported that AICAR increased endurance in untrained mice. AICAR is explicitly prohibited by WADA as a metabolic modulator (S4.5.2) on the 2026 Prohibited List.
Molecular Targets
- AMP-activated protein kinase (AMPK, allosteric via ZMP)
- PGC-1α (downstream)
- PPARδ (downstream)
Signaling Pathways
- AMPK / mTORC1 antagonism
- Mitochondrial biogenesis (PGC-1α)
- Fatty-acid oxidation (acetyl-CoA carboxylase inhibition)
Research Applications
The published evidence base is dominated by preclinical work (mice, isolated cells) plus small Phase II/III human trials in perioperative cardiac surgery (acadesine in CABG). Clinical development as a cardioprotective adjuvant was discontinued in the early 2010s.
Clinical Status
Regulatory Status AICAR / acadesine is NOT approved as a drug by the FDA, EMA, MHRA or any other Western regulator. A Phase III trial in CABG surgery (RED-CABG, Schering-Plough/Merck) was terminated in 2010 for lack of efficacy. WADA 2026 Prohibited List: section S4.5.2 (metabolic modulators — AMPK activators), prohibited in- and out-of-competition. Show more Show less
Sponsor
Historic: Schering-Plough / Merck (RED-CABG); development discontinued
Safety Profile
Observed in research settings
Limited human data. In perioperative Phase II/III trials, AICAR was described as generally tolerable with dose-limiting hyperuricaemia and transient cardiovascular effects. Observed in research settings.
Adverse Events Reported in Studies
- Hyperuricaemia (dose-limiting in human trials)
- Transient hypotension during IV infusion (reported)
- Headache, nausea (reported)
References
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Corton JM, Gillespie JG, Hawley SA, Hardie DG 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? European Journal of Biochemistry 1995;229(2):558-565. 1995 .
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Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM AMPK and PPARdelta agonists are exercise mimetics Cell 2008;134(3):405-415. 2008 .
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Drew BG, Kingwell BA Acadesine, an adenosine-regulating agent with the potential for widespread indications Expert Opinion on Pharmacotherapy 2008;9(12):2137-2144. 2008 .
Frequently Asked Questions
Is AICAR a peptide?
No. AICAR is a purine nucleoside analogue (a small-molecule AMPK activator), not a peptide. It is listed in this catalog alongside the research peptides for operational reasons.
Is AICAR permitted for athletes?
No. AICAR is on the WADA 2026 Prohibited List under section S4.5.2 (metabolic modulators — AMPK activators), prohibited both in- and out-of-competition.
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