OnePin Peptide Library · Metabolic
AICAR
AICA Riboside · Acadesine · Z-Riboside
AICAR (5-aminoimidazole-4-carboxamide ribonucleotide, also called acadesine) is an intermediate in de novo purine biosynthesis and an activator of AMP-activated protein kinase (AMPK) - the cellular master switch for energy-deficit signaling. It is not FDA-approved for any human indication. Clinically it has been investigated as an adjunct in acute myeloid leukemia, as an ischemia-reperfusion adjunct in cardiac surgery, and in metabolic disease models, but no approval has emerged.
Typical off-label protocols dose 50-100 mg subcutaneously once daily, often pre-workout, though the 8-minute half-life means any pre-workout timing benefit is brief. Reconstitute with bacteriostatic water and use within 1-2 weeks refrigerated. Expect subtle-to-absent subjective effects - AICAR does not produce the CNS stimulation of yohimbine or clenbuterol.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
How it works
AICAR enters cells via adenosine transporters and is phosphorylated intracellularly to ZMP (AICA ribotide monophosphate), a direct AMP-mimetic that allosterically activates AMP-activated protein kinase (AMPK). AMPK is a heterotrimeric kinase that senses cellular energy status via the AMP:ATP ratio and, when activated, shifts metabolism from ATP consumption to ATP production - increasing fatty acid oxidation, glucose uptake via GLUT4, mitochondrial biogenesis (via PGC-1-alpha upregulation), and autophagy, while suppressing lipogenesis, gluconeogenesis, and anabolic protein synthesis.
AICAR enters cells via adenosine transporters and is phosphorylated intracellularly to ZMP (AICA ribotide monophosphate), a direct AMP-mimetic that allosterically activates AMP-activated protein kinase (AMPK). AMPK is a heterotrimeric kinase that senses cellular energy status via the AMP:ATP ratio and, when activated, shifts metabolism from ATP consumption to ATP production - increasing fatty acid oxidation, glucose uptake via GLUT4, mitochondrial biogenesis (via PGC-1-alpha upregulation), and autophagy, while suppressing lipogenesis, gluconeogenesis, and anabolic protein synthesis.
In rodent skeletal muscle, chronic AICAR administration increases slow-twitch (oxidative) fiber proportion, raises mitochondrial density, and improves endurance running time even in sedentary animals - the effect that produced the 'exercise mimetic' framing. In humans, the very short plasma half-life (~8 minutes) and poor tissue delivery have limited effect size, and most published human studies have been small safety/pharmacokinetic trials rather than efficacy trials for endurance.
AICAR is not a receptor agonist and does not bind a hormone receptor - it acts through the intracellular AMPK pathway. It is typically administered parenterally (subcutaneous or intravenous) because oral bioavailability is extremely poor. Because AMPK activation is broad and tissue-non-selective, off-target metabolic effects are theoretically possible - most notably transient hyperuricemia from the purine load.
What to expect
First 1-2 weeks: subtle or absent subjective effects. No CNS stimulation. Some users report modestly reduced perceived exertion during steady-state cardio.
Week 2-4: cellular adaptations (AMPK-driven transcriptional shifts, mitochondrial biogenesis) accumulate but are not clinically perceptible in most users.
Week 4-8: peak theoretical benefit. Human evidence for the 'exercise mimetic' claim is weak - expect modest or unnoticeable practical effects in a trained human. The rodent magnitude has not translated.
Evidence
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Side effects & safety
Commonly reported
- Injection site reaction (mild erythema, tenderness)
- Transient hyperuricemia (elevated uric acid) at higher doses
- Occasional GI upset at higher doses
- Mild headache
Less common & notes
- Gout flare in susceptible individuals due to purine pool loading.
- Hypoglycemia if combined with insulin or sulfonylureas (AMPK increases glucose uptake).
- Cardiac ischemia-reperfusion research has documented arrhythmia signals at high IV doses, though the SubQ community doses are much lower.
- Long-term safety of chronic AMPK activation in humans is unknown - AMPK suppresses anabolic protein synthesis, so prolonged high-dose use may theoretically impair muscle growth.
- No approved human indication means the safety data set is thin compared to FDA-approved compounds.
Pharmacokinetics
Storage. Lyophilized vial: store refrigerated (2-8°C / 36-46°F) or frozen (-20°C) for long-term storage. Protect from light. After reconstitution with bacteriostatic water: refrigerate and use within 1-2 weeks. Do not freeze reconstituted solution. Discard if solution becomes cloudy or discolored.
Regulatory status
Not FDA-approved for any human indication in the United States. Investigated clinically as acadesine for acute myeloid leukemia and cardiac ischemia-reperfusion without achieving approval. Sold only as a research chemical / 'not for human use' peptide through research-supply vendors. Prohibited by the World Anti-Doping Agency (WADA) under class S4 (hormone and metabolic modulators) both in and out of competition. Not a controlled substance under the Controlled Substances Act, but sale for human use is prohibited by FDA regulation.
Put it to work
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Open AICAR straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.
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The guide & community
The complete AICAR walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.
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