Aniracetam

Overview

Aniracetam is a non-peptide pyrrolidinone derivative and positive allosteric modulator of AMPA-type glutamate receptors. It is marketed as a prescription drug for cognitive disorders in some European countries (Italy, Greece) but has never been approved by the US FDA as either a drug or dietary supplement ingredient. The compound was reportedly withdrawn from the Japanese market following a failed confirmatory trial. Despite lacking US regulatory approval, aniracetam is openly sold online by nootropic-supplement retailers, often with significant label-accuracy problems.

Mechanism of Action

Aniracetam is a positive allosteric modulator of AMPA-type ionotropic glutamate receptors. X-ray crystallographic and electrophysiological work on the GluA2 ligand-binding domain demonstrates that aniracetam binds at the dimer interface, on the twofold axis of molecular symmetry, adjacent to the hinge of the clamshell-like ligand-binding core. This binding stabilizes the closed-cleft, glutamate-bound conformation and slows receptor deactivation and desensitization, a mechanism distinct from piracetam's binding site.

Research Summary

The principal human efficacy evidence is one 6-month, double-blind, placebo-controlled multicenter trial in 109 elderly patients meeting probable-Alzheimer's criteria, which showed significant improvement in psychobehavioral parameters versus placebo with excellent reported tolerability, though no itemized adverse-event breakdown was available. No long-term (multi-year) human safety data were located, and no interventional trials of aniracetam are currently registered on ClinicalTrials.gov. In rodent models, aniracetam (50 mg/kg/day for 10 postnatal days) reversed prenatal-ethanol-induced avoidance-learning deficits in rat offspring and increased AMPA-receptor-mediated synaptic currents in hippocampal CA1 pyramidal cells. However, oral aniracetam (50 mg/kg, 5 days/week for 6 weeks) produced no cognitive or behavioral enhancement in healthy adult C57BL/6J mice across a comprehensive test battery.

Reported Side Effects

• Tolerability reported as 'excellent' in one 6-month trial, but no itemized adverse-event data available
• No long-term (multi-year) human safety data located
• Regulatory withdrawal in Japan following failed confirmatory trial suggests inconsistent efficacy/safety signal
• Substantial label-accuracy problems in commercial supplements (underdosing and supratherapeutic overdosing)
• Purity and identity risks in unregulated nootropic products

Compare Aniracetam with Others

Research References

• Aniracetam, CID 2196 (PubChem Compound Summary).
• Mechanism of positive allosteric modulators acting on AMPA receptors. 2005. PMID 16192394.
• Aniracetam (Ro 13-5057) in the treatment of senile dementia of Alzheimer type (SDAT): results of a placebo controlled multicentre clinical study. 1991. PMID 1822317.
• Aniracetam reversed learning and memory deficits following prenatal ethanol exposure by modulating functions of synaptic AMPA receptors. 2008. PMID 17609677.

Frequently asked questions

Has Aniracetam been independently lab-tested?

Disclosed Labs has collected 2 Certificates of Analysis (COA) for Aniracetam from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 99.5% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/aniracetam/testing.

How does Aniracetam work?

Aniracetam is a positive allosteric modulator of AMPA-type ionotropic glutamate receptors. X-ray crystallographic and electrophysiological work on the GluA2 ligand-binding domain demonstrates that aniracetam binds at the dimer interface, on the twofold axis of molecular symmetry, adjacent to the hinge of the clamshell-like ligand-binding core. This binding stabilizes the closed-cleft, glutamate-bound conformation and slows receptor deactivation and desensitization, a mechanism distinct from piracetam's binding site.

What does the research say about Aniracetam?

The principal human efficacy evidence is one 6-month, double-blind, placebo-controlled multicenter trial in 109 elderly patients meeting probable-Alzheimer's criteria, which showed significant improvement in psychobehavioral parameters versus placebo with excellent reported tolerability, though no itemized adverse-event breakdown was available. No long-term (multi-year) human safety data were located, and no interventional trials of aniracetam are currently registered on ClinicalTrials.gov. In rodent models, aniracetam (50 mg/kg/day for 10 postnatal days) reversed prenatal-ethanol-induced avoidance-learning deficits in rat offspring and increased AMPA-receptor-mediated synaptic currents in hippocampal CA1 pyramidal cells. However, oral aniracetam (50 mg/kg, 5 days/week for 6 weeks) produced no cognitive or behavioral enhancement in healthy adult C57BL/6J mice across a comprehensive test battery.