AICAR

AICAR Peptide Research & Scientific Overview

Jump to: Structure | Mechanism | Studies | Pharmacokinetics | Protocols | Limitations | Lead Researcher | References

AICAR Molecular Structure & Chemical Properties

AICAR, or 5-aminoimidazole-4-carboxamide ribonucleoside, represents one of the most extensively studied AMPK activators in metabolic research, with investigations spanning over three decades examining its effects on cellular energy metabolism. Originally identified as an intermediate in the purine nucleotide biosynthesis pathway, this adenosine analog has demonstrated remarkable ability to activate AMP-activated protein kinase without requiring actual cellular energy depletion. Unlike most pharmacological compounds that indirectly influence metabolism through receptor binding, AICAR enters cells via adenosine transporters and undergoes phosphorylation by adenosine kinase to form ZMP, an AMP-mimetic that directly activates the cellular energy sensor AMPK. This unique mechanism has established AICAR as a fundamental research tool for investigating energy metabolism, mitochondrial biogenesis, and metabolic disease pathways.

Chemical Structure

2D molecular structure (Source: PubChem)

Technical Specifications

The molecule consists of an imidazole ring with amino and carboxamide groups attached to a ribose sugar moiety. Upon cellular uptake, AICAR is rapidly phosphorylated to ZMP, which accumulates to millimolar concentrations within cells and functions as the active AMP-mimetic compound.

AICAR Mechanism of Action

AICAR peptide exerts its biological effects primarily through activation of AMP-activated protein kinase, though research has revealed both AMPK-dependent and AMPK-independent mechanisms. After cellular uptake via adenosine transporters, AICAR is phosphorylated by adenosine kinase to form ZMP (AICAR monophosphate), which binds to the gamma-subunit of AMPK and mimics the allosteric activation normally triggered by rising AMP levels during energy depletion. This activation initiates a cascade of metabolic reprogramming that fundamentally alters cellular energy utilization and biosynthetic capacity.

Primary Cellular Pathways

AMPK Activation – Energy Sensing

Research has demonstrated that ZMP binds to site 3 on the AMPK gamma-subunit, causing conformational changes that promote phosphorylation of threonine-172 on the alpha-subunit by upstream kinases[1]. This activation enables:

• Enhanced glucose uptake through GLUT4 translocation to cell membranes
• Increased fatty acid oxidation via inhibition of acetyl-CoA carboxylase
• Suppression of ATP-consuming anabolic pathways including protein and lipid synthesis
• Activation of mitochondrial biogenesis through PGC-1 alpha signaling

Studies using AMPK knockout models have confirmed that many metabolic effects of AICAR require functional AMPK, though the magnitude of response varies by tissue type[2].

mTOR Pathway Inhibition – Protein Synthesis Regulation

AICAR influences mechanistic target of rapamycin signaling in an AMPK-dependent manner, inhibiting mTORC1 while activating mTORC2[3]. Key findings include:

• Reduced phosphorylation of S6 kinase 1 and 4E-BP1, downstream targets of mTORC1
• Decreased protein synthesis rates in skeletal muscle
• Enhanced autophagy through mTORC1 suppression
• Cell cycle arrest in rapidly dividing cells

The dual effects on mTOR complexes demonstrate the complexity of AICAR’s impact on cellular growth and metabolism.

Mitochondrial Biogenesis – Oxidative Capacity Enhancement

Investigations have shown that AICAR treatment increases expression of genes involved in mitochondrial function and oxidative metabolism[4]. This mechanism involves:

• Upregulation of PGC-1 alpha, the master regulator of mitochondrial biogenesis
• Increased expression of SIRT1 and SIRT3, protein deacetylases that regulate metabolism
• Enhanced oxidative enzyme activity including cytochrome c oxidase
• Fiber type transformation toward more oxidative muscle phenotypes

Studies in sedentary mice demonstrated that four weeks of AICAR treatment increased oxidative gene expression and enhanced running endurance by 44 percent, mimicking some effects of exercise training[5].

Glucose and Lipid Metabolism Modulation

Research in insulin-resistant animal models has documented AICAR’s effects on substrate metabolism[6]:

• Increased insulin-independent glucose uptake in skeletal muscle
• Suppression of hepatic glucose production through inhibition of gluconeogenic enzymes
• Enhanced fatty acid oxidation through reduced malonyl-CoA levels
• Decreased lipid accumulation in liver and muscle tissues

These metabolic shifts occur through both direct AMPK-mediated phosphorylation of metabolic enzymes and transcriptional regulation of metabolic genes.

AMPK-Independent Effects

Systematic reviews have identified numerous AICAR effects that persist in AMPK-deficient models[7]. Evidence includes:

• Direct inhibition of fructose-1,6-bisphosphatase as an AMP-mimetic
• Modulation of purine nucleotide synthesis pathways
• Cell cycle effects through accumulation of ZMP as a purine intermediate
• Inhibition of RyR1 calcium leak independent of AMPK activation

AICAR Research Applications & Key Findings

Metabolic Disease Research

Diabetes and Insulin Resistance Studies

Extensive research in rodent models of type 2 diabetes has examined AICAR’s effects on glucose homeostasis and insulin sensitivity[8]. Key findings include:

• Reduced blood glucose levels in ob/ob and db/db mice following both acute and chronic administration
• Increased glucose uptake in skeletal muscle independent of insulin signaling
• Suppression of hepatic glucose output through inhibition of gluconeogenesis
• Enhanced insulin sensitivity in high-fat diet-fed rats with established insulin resistance

Studies using euglycemic-hyperinsulinemic clamp techniques demonstrated that a single AICAR dose improved whole-body insulin action in insulin-resistant rats, with effects persisting 24 hours after administration[9]. However, chronic treatment also elevated serum triglyceride levels in some models, indicating complex metabolic trade-offs.

Obesity and Lipid Metabolism Research

Investigations in genetic and diet-induced obesity models have shown effects on body composition and lipid metabolism[10]:

• Prevention of weight gain in high-fat diet-fed rodents
• Reduced adipose tissue mass through enhanced fatty acid oxidation
• Decreased liver triglyceride accumulation
• Improved circulating lipid profiles in some but not all animal models

Research in Zucker fatty rats demonstrated that AICAR prevented diabetes development and protected pancreatic islet beta-cells from degranulation[11].

Exercise Physiology Research

Endurance and Mitochondrial Adaptation

AICAR has been extensively studied as an “exercise mimetic” for its ability to induce some adaptations typically associated with endurance training[12]. Research findings include:

• Enhanced running endurance by 44 percent in sedentary mice after four weeks of treatment
• Increased expression of oxidative metabolism genes similar to exercise training
• Improved mitochondrial enzyme activity and mitochondrial biogenesis
• Fiber type transformation toward slow-twitch oxidative muscle fibers

Studies combining AICAR with exercise training showed synergistic effects when co-administered with PPARdelta agonists, producing greater adaptations than either intervention alone[13]. However, the benefits were primarily metabolic rather than complete exercise mimicry.

Skeletal Muscle Function in Aging

Research in aged mice has demonstrated that chronic AICAR treatment can partially reverse age-related declines in muscle function[14]:

• Preserved muscle mass and force production in old mice
• Restored expression of many genes to youthful levels
• Reduced expression of muscle atrophy markers MAFbx and MuRF1
• Improved treadmill running performance in aged animals

These effects correlated with increased mitochondrial enzyme content and enhanced AMPK signaling in aged muscle tissue.

Cardiovascular Research

Ischemic Injury Protection

Studies in cardiac ischemia models have examined AICAR’s protective effects during periods of reduced blood flow[15]:

• Reduced infarct size in heart tissue following ischemia-reperfusion injury
• Enhanced nucleotide resynthesis during myocardial ischemia
• Improved cardiac function recovery after ischemic episodes
• Protection against arrhythmias in some experimental models

The compound was initially developed under the name acadesine for potential use in cardiac protection during surgery, though clinical development did not advance to approval.

Vascular Function Studies

Research has documented effects on blood vessel function and vascular smooth muscle[16]:

• Promotion of endothelium-independent vasorelaxation through AMPK activation
• Increased nitric oxide pathway activity
• Reduced vascular inflammation in atherosclerosis models
• Protection against endothelial dysfunction in metabolic disease models

Neurological Research

Cognitive Function and Neuroprotection

Investigations in rodent models have examined AICAR’s effects on brain function[17]:

• Enhanced hippocampal neurogenesis after seven days of treatment
• Increased brain-derived neurotrophic factor levels in young and aged mice
• Improved cognitive performance and motor coordination in behavioral tests
• Transient benefits that did not persist with prolonged treatment

However, extended AICAR treatment beyond two weeks showed concerning effects including upregulation of inflammatory markers and pro-apoptotic genes in brain tissue, contrasting sharply with the sustained benefits of exercise[18].

Cancer Research

Tumor Growth Inhibition

Studies in various cancer cell lines have documented anti-proliferative effects[19]:

• Inhibition of glioblastoma cell growth through suppression of lipid synthesis
• Cell cycle arrest in multiple cancer cell types
• Enhanced radiosensitivity when combined with radiation therapy
• Preferential toxicity for cancer cells versus normal cells in some models

Research in EGFR-activated glioblastomas showed that AICAR was more effective than rapamycin at blocking tumor cell proliferation, primarily through inhibition of fatty acid and cholesterol synthesis[20].

AICAR Pharmacokinetics & Metabolism

Absorption & Distribution

AICAR exhibits unusual pharmacokinetic properties that significantly limit its therapeutic potential despite promising preclinical efficacy[21]. Following administration in animal and human studies:

• Oral bioavailability less than 5 percent when administered in solution
• Intravenous injection provides immediate systemic exposure with rapid cellular uptake
• Cell membrane penetration via adenosine transporters
• Rapid phosphorylation by adenosine kinase to form the active metabolite ZMP

Distribution studies have demonstrated that AICAR enters various tissues including skeletal muscle, liver, heart, and brain tissue, with ZMP accumulating to millimolar concentrations within cells despite low extracellular concentrations[22].

Metabolism & Elimination

The metabolic fate of AICAR follows pathways related to purine nucleotide metabolism[23]:

• Plasma elimination half-life of 1.4 hours in human subjects following intravenous administration
• Intracellular conversion to ZMP by adenosine kinase
• Further metabolism by AICAR transformylase in the purine synthesis pathway
• Potential dephosphorylation back to AICAR by cytosolic nucleotidases

A notable characteristic is that intracellular ZMP concentrations remain elevated for hours after plasma AICAR clearance, providing prolonged AMPK activation despite rapid systemic elimination. This disconnect between plasma pharmacokinetics and cellular pharmacodynamics complicates dose-response relationships.

Excretion Pathways

Limited human pharmacokinetic data indicates[24]:

• Renal excretion as the primary elimination route
• Rapid clearance from circulation requiring continuous infusion for sustained effects
• Accumulation of naturally occurring AICAR in individuals with certain metabolic disorders
• Detection window of several hours in blood following administration

The short half-life and poor oral bioavailability have rendered AICAR unsuitable for chronic treatment of metabolic disorders, despite its potent metabolic effects in preclinical studies.

AICAR Research Protocols & Administration

Dosing in Published Research

Research investigations have employed diverse AICAR doses depending on species, model, administration route, and research objectives:

• Mouse studies: 100-500 mg/kg body weight subcutaneously or intraperitoneally for acute effects; 0.5-1.0 mg/g/day for chronic studies
• Rat models: 250-400 mg/kg body weight for acute metabolic studies; continuous infusion at 20-200 mg/kg/day for prolonged effects
• Human studies (limited): Intravenous infusions at approximately 1 gram/kg/day for cardiac protection trials; 50-100 mg/kg bolus followed by continuous infusion in clinical investigations
• Cell culture: 0.5-2.0 mM for 30 minutes to 24 hours depending on endpoint measurements

Important: These are experimental doses used in animal and research studies and cannot be extrapolated to other species due to profound differences in adenosine kinase activity, AMPK expression levels, tissue distribution patterns, and metabolic clearance rates. Species-specific pharmacokinetic and pharmacodynamic factors fundamentally influence both efficacy and safety profiles.

Administration Routes in Research

Multiple delivery methods have been investigated in preclinical and clinical studies:

• Intravenous injection – Most common route in human studies; provides immediate systemic exposure but requires continuous infusion for sustained effects
• Intraperitoneal injection – Standard route in rodent research; reliable absorption and systemic distribution
• Subcutaneous injection – Used in many animal studies including exercise mimetic research; slower absorption than intravenous route
• Oral administration – Severely limited by poor bioavailability (less than 5 percent); not viable for chronic treatment
• Continuous infusion – Employed in some chronic animal studies using osmotic minipumps to maintain steady plasma levels

The requirement for parenteral administration represents a significant barrier to clinical application for chronic metabolic disorders.

Common Model Organisms

AICAR has been studied across multiple species and experimental systems:

• Mice – Primary research model for metabolic and exercise studies (C57BL/6, ob/ob, db/db strains); extensive use in knockout and transgenic models
• Rats – Employed in diabetes research (Zucker fatty, Zucker diabetic fatty, Wistar, Sprague-Dawley strains); insulin resistance and cardiovascular studies
• Humans – Limited clinical trials focused on cardiac ischemia protection and acute metabolic effects; pharmacokinetic characterization studies in healthy volunteers
• Cell culture – Skeletal muscle myotubes (C2C12, L6), hepatocytes, endothelial cells, cancer cell lines; mechanistic studies of AMPK signaling
• Canine models – Used in some cardiovascular protection studies

Research Limitations & Regulatory Status

Critical Gaps in Current Evidence

Despite decades of preclinical research demonstrating metabolic benefits in animal models, AICAR faces substantial translational barriers that have prevented clinical development for metabolic diseases.

Lack of Human Clinical Data

The most significant limitation is the paucity of published human clinical trials beyond acute cardiac protection studies:

• No approved therapeutic applications in humans for any indication
• Limited human pharmacokinetic data available only from small early-phase trials
• No large-scale efficacy trials in metabolic diseases despite promising animal data
• Long-term human safety profile completely unestablished
• Optimal dosing regimens for metabolic indications unknown

Early clinical trials in the 1990s focused on cardiac protection during surgery but did not result in regulatory approval or widespread clinical adoption[25].

Pharmacokinetic Limitations

Fundamental pharmacokinetic properties severely limit clinical utility:

• Poor oral bioavailability (less than 5 percent) renders oral dosing impractical
• Short plasma half-life (1.4 hours) requires continuous intravenous infusion
• Elevated lactic acid and uric acid levels reported in human subjects at therapeutic doses
• No suitable oral formulations or long-acting analogs currently available

These properties make AICAR unsuitable for chronic treatment of metabolic disorders that would require sustained daily dosing[26].

AMPK-Independent Effects

Research has revealed that many AICAR effects occur independently of AMPK activation:

• Functions as an AMP-mimetic that activates other AMP-dependent enzymes including fructose-1,6-bisphosphatase
• Accumulates as ZMP in purine biosynthesis pathways, affecting cell proliferation
• Direct effects on ion channels and calcium homeostasis unrelated to AMPK
• Variable tissue responses based on local enzyme expression patterns

These AMPK-independent actions complicate interpretation of research findings and raise concerns about off-target effects[27].

Long-Term Safety Considerations

Critical safety questions remain unanswered:

• Chronic treatment effects beyond several weeks unstudied even in animals
• Potential for excessive AMPK activation in inappropriate tissues
• Effects on cell division and cancer risk with prolonged exposure uncertain
• Cardiovascular safety with extended use not established
• Interactions with medications uncharacterized in human populations

Research showing inflammatory marker upregulation and pro-apoptotic gene expression with prolonged treatment in brain tissue raises additional safety concerns[28].

Regulatory & Competitive Sport Status

FDA Position

AICAR has not received FDA approval for any therapeutic indication:

• Classified as an investigational new drug
• No approved medical applications in humans
• Not recognized as safe and effective for treating any condition
• Not available for medical use outside of approved clinical trials
• Previously studied in early-phase clinical trials for cardiac protection without advancing to approval

The compound remains restricted to research applications under appropriate institutional oversight.

WADA Prohibition

The World Anti-Doping Agency classifies AICAR as a prohibited substance for competitive athletes:

• Listed under S4.5 (Metabolic Modulators) on the Prohibited List since 2009
• Prohibited at all times (in and out of competition)
• No Therapeutic Use Exemptions available
• Detection methods established using liquid chromatography-mass spectrometry

WADA’s prohibition reflects concerns about performance enhancement through metabolic manipulation and the lack of regulatory approval for human use[29]. Detection thresholds have been established based on naturally occurring AICAR levels in athletes.

Research Classification: AICAR is available only for laboratory research use under appropriate ethical oversight. It is not intended for human consumption, medical use, diagnostic purposes, or veterinary applications. Research must be conducted in compliance with institutional review board approval and applicable regulatory requirements.

Boston University School of Medicine, Boston, Massachusetts

Dr. Neil Ruderman has been a pioneering figure in AMPK research since the identification of this critical metabolic enzyme, contributing extensively to understanding AICAR’s effects on metabolism and insulin resistance. His laboratory at Boston University conducted seminal research demonstrating that AMPK activation could improve insulin sensitivity and glucose metabolism in animal models of metabolic syndrome.

Dr. Ruderman’s research contributions include:

• Early investigations of AMPK’s role in exercise-induced metabolic adaptations
• Studies demonstrating AICAR’s effects on glucose uptake and fatty acid oxidation in insulin-resistant states
• Research linking AMPK activation to improvements in metabolic syndrome phenotypes
• Investigations of the relationship between AMPK, malonyl-CoA regulation, and lipid metabolism
• Work elucidating mechanisms by which AMPK modulates insulin sensitivity

His collaborative research helped establish the foundation for understanding AMPK as a therapeutic target for metabolic diseases, though the pharmacokinetic limitations of AICAR have prevented clinical translation. Dr. Ruderman’s work has been instrumental in advancing the field’s understanding of cellular energy sensing and metabolic regulation.

Disclaimer: This spotlight is provided for educational purposes to acknowledge scientific contributions to AICAR and AMPK research. Cenexa Labs has no affiliation with Dr. Ruderman or Boston University School of Medicine, and this information does not constitute an endorsement of any products or services.

References

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2. Jorgensen, S.B., Viollet, B., Andreelli, F., Frosig, C., Birk, J.B., Schjerling, P., Vaulont, S., Richter, E.A., & Wojtaszewski, J.F. (2004). Knockout of the alpha2 but not alpha1 5′-AMP-activated protein kinase isoform abolishes 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranosidebut not contraction-induced glucose uptake in skeletal muscle. Journal of Biological Chemistry, 279(2), 1070-1079. PubMed
   
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5. Narkar, V.A., Downes, M., Yu, R.T., Embler, E., Wang, Y.X., Banayo, E., Mihaylova, M.M., Nelson, M.C., Zou, Y., Juguilon, H., Kang, H., Shaw, R.J., & Evans, R.M. (2008). AMPK and PPARdelta agonists are exercise mimetics. Cell, 134(3), 405-415. PubMed
   
6. Iglesias, M.A., Furler, S.M., Cooney, G.J., Kraegen, E.W., & Ye, J.M. (2004). AMP-activated protein kinase activation by AICAR increases both muscle fatty acid and glucose uptake in white muscle of insulin-resistant rats in vivo. Diabetes, 53(7), 1649-1654. PubMed
   
7. Vucicevic, L., Misirkic-Marjanovic, M., Harhaji-Trajkovic, L., Maric, N., & Trajkovic, V. (2021). AICAr, a widely used AMPK activator with important AMPK-independent effects: A systematic review. Cells, 10(5), 1095. PubMed
   
8. Buhl, E.S., Jessen, N., Pold, R., Ledet, T., Flyvbjerg, A., Pedersen, S.B., Pedersen, O., Schmitz, O., & Lund, S. (2002). Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. Diabetes, 51(7), 2199-2206. PubMed
   
9. Iglesias, M.A., Ye, J.M., Frangioudakis, G., Saha, A.K., Tomas, E., Ruderman, N.B., Cooney, G.J., & Kraegen, E.W. (2002). AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes, 51(10), 2886-2894. PubMed
   
10. Song, X.M., Fiedler, M., Galuska, D., Ryder, J.W., Fernstrom, M., Chibalin, A.V., Wallberg-Henriksson, H., & Zierath, J.R. (2002). 5-Aminoimidazole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice. Diabetologia, 45(1), 56-65. PubMed
    
11. Pold, R., Jensen, L.S., Jessen, N., Buhl, E.S., Schmitz, O., Flyvbjerg, A., Fujii, N., Goodyear, L.J., Gotfredsen, C.F., Brand, C.L., & Lund, S. (2005). Long-term AICAR administration and exercise prevents diabetes in ZDF rats. Diabetes, 54(4), 928-934. PubMed
    
12. Winder, W.W., Holmes, B.F., Rubink, D.S., Jensen, E.B., Chen, M., & Holloszy, J.O. (2000). Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. Journal of Applied Physiology, 88(6), 2219-2226. PubMed
    
13. Narkar, V.A., Downes, M., Yu, R.T., Embler, E., Wang, Y.X., Banayo, E., Mihaylova, M.M., Nelson, M.C., Zou, Y., Juguilon, H., Kang, H., Shaw, R.J., & Evans, R.M. (2008). AMPK and PPARdelta agonists are exercise mimetics. Cell, 134(3), 405-415. PubMed
    
14. Wilcox, H.G., Williams, S.E., Pegram, L.E., Schill, K.E., McKenzie, B.A., Washington, T.A., Rosa-Caldwell, M.E., Brown, J.L., Perry, R.A., & Greene, N.P. (2025). Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression. FASEB BioAdvances, 7(1), 49-60. PubMed
    
15. Folmes, C.D., Sowah, D., Clanachan, A.S., & Lopaschuk, G.D. (2009). High rates of residual fatty acid oxidation during mild ischemia decrease cardiac work and efficiency. Journal of Molecular and Cellular Cardiology, 47(1), 142-148. PubMed
    
16. Alesutan, I., Munoz, C., Sopjani, M., Dermaku-Sopjani, M., Michael, D., Fraser, S., Kemp, B.E., Seebohm, G., Foller, M., & Lang, F. (2011). Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. Biochemical and Biophysical Research Communications, 408(4), 505-510. PubMed
    
17. Kobilo, T., Guerrieri, D., Zhang, Y., Collica, S.C., Becker, K.G., & van Praag, H. (2014). AMPK agonist AICAR improves cognition and motor coordination in young and aged mice. Learning & Memory, 21(2), 119-126. PubMed
    
18. Guerrieri, D., & van Praag, H. (2015). Exercise-mimetic AICAR transiently benefits brain function. Oncotarget, 6(21), 18293-18313. PubMed
    
19. Rattan, R., Giri, S., Singh, A.K., & Singh, I. (2005). 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase. Journal of Biological Chemistry, 280(47), 39582-39593. PubMed
    
20. Grimaldi, C., Chiarini, F., Tabellini, G., Ricci, F., Tazzari, P.L., Battistelli, M., Falcieri, E., Bortul, R., Melchionda, F., Iacobucci, I., Pagliaro, P., Martinelli, G., Pession, A., Barata, J.T., McCubrey, J.A., & Martelli, A.M. (2012). AMP-dependent kinase/mammalian target of rapamycin complex 1 signaling in T-cell acute lymphoblastic leukemia: therapeutic implications. Leukemia, 26(1), 91-100. PubMed
    
21. Dixon, R., Gourzis, J., McDermott, D., Fujitaki, J., Dewland, P., & Gruber, H. (1991). AICA-riboside: Safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent. Journal of Clinical Pharmacology, 31(4), 342-347. PubMed
    
22. Corton, J.M., Gillespie, J.G., Hawley, S.A., & Hardie, D.G. (1995). 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? European Journal of Biochemistry, 229(2), 558-565. PubMed
    
23. Sabina, R.L., Patterson, D., & Holmes, E.W. (1985). 5-Amino-4-imidazolecarboxamide riboside (Z-riboside) metabolism in eukaryotic cells. Journal of Biological Chemistry, 260(10), 6107-6114. PubMed
    
24. Dixon, R., Gourzis, J., McDermott, D., Fujitaki, J., Dewland, P., & Gruber, H. (1991). AICA-riboside: Safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent. Journal of Clinical Pharmacology, 31(4), 342-347. PubMed
    
25. Mangano, D.T., & Investigators of the Multicenter Study of Perioperative Ischemia Research Group. (1997). Effects of acadesine on myocardial infarction, stroke, and death following surgery. Journal of the American Medical Association, 277(4), 325-332. PubMed
    
26. Vucicevic, L., Misirkic-Marjanovic, M., Harhaji-Trajkovic, L., Maric, N., & Trajkovic, V. (2021). AICAr, a widely used AMPK activator with important AMPK-independent effects: A systematic review. Cells, 10(5), 1095. PubMed
    
27. Vucicevic, L., Misirkic-Marjanovic, M., Harhaji-Trajkovic, L., Maric, N., & Trajkovic, V. (2021). AICAr, a widely used AMPK activator with important AMPK-independent effects: A systematic review. Cells, 10(5), 1095. PubMed
    
28. Guerrieri, D., & van Praag, H. (2015). Exercise-mimetic AICAR transiently benefits brain function. Oncotarget, 6(21), 18293-18313. PubMed
    
29. World Anti-Doping Agency. (2024). The World Anti-Doping Code International Standard: Prohibited List. WADA
    

All references open in new window. These citations are provided for educational and research purposes only. This information is not intended to diagnose, treat, cure, or prevent any disease. AICAR is intended for laboratory research use only.