AICAR
Acadesine / AICA Ribonucleotide / ZMP
AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide, also known as Acadesine) is a synthetic analog of adenosine monophosphate that directly activates AMP-activated protein kinase (AMPK), the master cellular energy sensor. Originally developed as a cardioprotective agent for use during cardiac surgery, it gained notoriety as an "exercise mimetic" capable of triggering metabolic adaptations typically associated with endurance training. AICAR is banned by the World Anti-Doping Agency (WADA) and is classified as a metabolic modulator on the prohibited substances list.
Mechanism of Action
AMP-kinase activator that mimics the metabolic effects of exercise. Increases fatty acid oxidation, glucose uptake, and mitochondrial biogenesis through direct AMPK phosphorylation. Shifts cellular metabolism toward an endurance-trained state.
Research Protocols
For research purposes only. Not medical advice.
Research protocols use 150-500mg daily via subcutaneous injection. Animal studies used 500mg/kg. Often cycled 4-8 weeks. Sometimes combined with GW501516 in research settings.
Research Notes
Clinical Research Status
AICAR underwent Phase III clinical trials for reduction of ischemic injury during coronary artery bypass graft surgery, though it ultimately did not receive FDA approval for this indication. Research interest shifted dramatically after 2008 Salk Institute studies demonstrated that AICAR administration alone could improve running endurance in sedentary mice by 44%. It remains an investigational compound with no approved medical indications, though academic research into AMPK activation continues across metabolic disease, cancer, and aging fields.
Key Published Findings
The landmark Narkar et al. (2008) paper in Cell demonstrated that AICAR treatment for 4 weeks reprogrammed muscle metabolism toward oxidative fiber types and enhanced running endurance without exercise training. AMPK activation by AICAR increases fatty acid oxidation, glucose uptake, and mitochondrial biogenesis through PGC-1alpha signaling pathways. In cardiac ischemia studies, AICAR reduced post-surgical complications including atrial fibrillation and the need for inotropic support.
Safety Profile
Clinical trial data from cardiac surgery studies showed AICAR to be relatively well-tolerated at therapeutic doses, with hypoglycemia and lactic acidosis being the primary dose-limiting concerns. Renal toxicity has been observed at higher doses due to uric acid accumulation from purine metabolism. Long-term safety data in healthy populations is essentially nonexistent, as most human data comes from short-term perioperative use in cardiac patients.
Comparison to Related Compounds
Unlike GW501516 (Cardarine), which activates PPAR-delta downstream of AMPK, AICAR directly activates AMPK itself, affecting a broader range of metabolic pathways including autophagy and mTOR suppression. SLU-PP-332 represents a newer generation of exercise mimetics targeting estrogen-related receptors rather than AMPK. Metformin also activates AMPK but through indirect mitochondrial complex I inhibition rather than direct allosteric activation, resulting in a different pharmacological profile.
Community Observations
Users report enhanced endurance and fat oxidation, though the effects are considered modest compared to expectations set by animal studies. The high cost per effective dose and requirement for injection limit its practical use in performance enhancement contexts. Some users combine AICAR with GW501516 based on the original Salk Institute research showing synergistic effects, though this combination carries compounded safety unknowns.
Half-Life
~2-3 hours
Reconstitution
Bacteriostatic water (BAC) or sterile saline
Storage
Lyophilized
Refrigerate 2-8C up to 12 months.
Reconstituted
Refrigerate 2-8C. Use within 14 days.
US Legal Status
Also Known As
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