Peptides›Metabolic›AICAR

AICAR

/ Synthetic AMP-mimetic small molecule; AMPK activator (acadesine)

TIER 2 · TranslationalN = 0 · TESTING PENDINGMW 258.23 g·mol⁻¹

ALIAS · Acadesine · AICAR · AICA-riboside · 5-Aminoimidazole-4-carboxamide ribonucleoside

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequence— sequence not captured —

MW · 258.23CLASS · Synthetic AMP-mimetic small molecule; AMPK activator (acadesine)CATEGORY · Metabolic

Tier 2. Rodent exercise-mimetic literature (Narkar 2008) and small Phase 1-style human exposure data exist. WADA-banned since 2009 as an unapproved metabolic modulator. Approved in some regions historically for diagnostic and intraoperative cardioprotection use; not FDA-approved in the US as a chronic-administration therapeutic.

§ B · Mechanism of action

AICAR is a cell-permeable nucleoside that is intracellularly phosphorylated to ZMP (5-aminoimidazole-4-carboxamide ribotide), a structural mimetic of AMP. ZMP allosterically activates AMP-activated protein kinase (AMPK), the cellular energy-status sensor, producing downstream effects characteristic of low-energy state: increased fatty-acid oxidation, glucose uptake, mitochondrial biogenesis (PGC-1alpha induction), and inhibition of anabolic pathways (mTOR, lipogenesis). The Narkar 2008 rodent paper framed AICAR as an exercise-mimetic by showing endurance-capacity gains in sedentary mice.

§ C · Human clinical evidence

Tier 2. Rodent metabolic and endurance literature is extensive. Human exposure data are limited - small Phase 1-style studies reported acute infusion AMPK-pathway pharmacodynamic effects on glucose flux and substrate handling. Cuthbertson 2007 (Diabetes) reported acute intravenous AICAR effects on glucose disposal and substrate oxidation in healthy male volunteers. No Phase 3 RCTs in any indication. Earlier interest as an intraoperative cardioprotective agent (acadesine, Phase 3 trials in CABG surgery in the 1990s) did not translate to approval.

§ D · Primary literature

PubMed18674809Narkar VA et al. — AMPK and PPARdelta agonists are exercise mimetics · Cell · rodentAICAR administered to sedentary mice for four weeks produced AMPK-dependent gene-expression changes and increased running endurance by approximately 44%; framed as pharmacological exercise mimicry.Limitations: Rodent only; single-laboratory result; ongoing debate over translational equivalence to human exercise adaptation.2008

PubMed17513706Cuthbertson DJ et al. — 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men · Diabetes · human-phase-1Acute intravenous AICAR infusion in healthy male volunteers stimulated skeletal-muscle 2-deoxyglucose uptake and AMPK-pathway pharmacodynamic markers; first direct human demonstration of AMPK-mediated glucose uptake.Limitations: Acute infusion only; small n; healthy male volunteers; no chronic-dosing data.2007

§ F · Safety signal

Acute human infusion data report transient hyperuricaemia, lactic acidosis at higher exposures, and asymptomatic transaminase elevations. No long-term or chronic-administration human safety database. WADA prohibited list inclusion (2009) reflects regulatory rather than safety judgement.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

The 'exercise-in-a-pill' framing from Narkar 2008 has been heavily repeated in vendor marketing without acknowledging that the rodent paradigm (sedentary mice, acute high-dose IP injection) has limited translational equivalence to chronic oral or subcutaneous administration in humans. WADA-prohibited status is a relevant disclosure for any reader engaged in tested-sport competition. Vendor-supplied AICAR purity and identity vary; analytical characterisation of research-grade material is uncommon.