Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of Aniracetam and NSI-189 — mechanism, side effects, legal status, and pricing.
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 The compound was reportedly withdrawn from the Japanese market following a failed confirmatory trial.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.
NSI-189 (INN: amdiglurax; developmental code ALTO-100) is a non-peptide small-molecule benzylpiperazine-aminopyridine derivative investigated as a neurogenic/neuroplasticity-modulating agent for major depressive disorder. It stimulates hippocampal neural progenitor proliferation and differentiation in vitro and neurogenesis in vivo (mouse), acting independently of monoamine reuptake pathways. NSI-189 has never been FDA-approved; Phase 2 monotherapy trials in MDD (220 patients, 2020) and a Phase 2b trial under Alto Neuroscience (~300 patients, 2024) both failed to meet primary MADRS endpoints, and it remains investigational only.
Aniracetam
NSI-189
Category
Legal Status
Mechanism
Side Effects
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Aniracetam
No pricing data yet.
Check Aniracetam prices →NSI-189
No pricing data yet.
Check NSI-189 prices →COA corpus from Disclosed Labs — independently tested batches only.
Aniracetam
2
COAs
99.5%
Avg purity
2
Labs
NSI-189
No COA data yet.
Submit testing data →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.
Key references
Human data exist from three registered trials: a Phase 1 single-dose PK study in healthy volunteers (NCT01310881), a Phase 1B multiple-dose-escalation study in 24 MDD patients (28-day inpatient dosing at 40 mg once/twice/thrice daily; half-life ~17.4–20.5 hours; no serious adverse events; no significant hippocampal volume change at day 28 or 84), and a Phase 2 double-blind, placebo-controlled trial in 220 MDD outpatients (12 weeks at 40 mg or 80 mg daily) that missed its primary MADRS endpoint at both doses (p=0.22 and p=0.34, respectively), with some significant secondary/patient-reported benefits at 40 mg. A Phase 2b trial under the ALTO-100 designation (~300 adults, 34 US sites, 6-week double-blind) also failed to meet its primary MADRS endpoint (topline October 2024). Preclinical findings include improved motor/neurological deficits sustained to 24 weeks in a rat stroke model (oral dosing starting 6 hours post-MCAO; increased hippocampal/cortical MAP2 neurite outgrowth; in vitro OGD/R assays showed reduced cell death and upregulated BDNF/SCF), reversal of motor and cognitive impairments in an Angelman syndrome mouse model (with mild performance enhancement in wild-type mice), improved Barnes maze memory retention in a 5xFAD Alzheimer's mouse model (conference abstract), and prevention of peripheral neuropathy indices with increased hippocampal neurogenesis/synaptic markers/volume and protected long-term memory in mouse and rat models of type 1 and type 2 diabetes, alongside enhanced mitochondrial function in a type 2 diabetic rat model.
Aniracetam and NSI-189 are both in the Cognitive category and may have overlapping mechanisms. Researchers should review both profiles carefully, understand the mechanisms of action, and monitor the relevant biomarkers when combining compounds in the same class. As always, consult a licensed healthcare provider before making any decisions about combining research compounds.
This platform provides informational tools only, not medical advice. This comparison is for educational purposes only. Consult a licensed provider.
Contraindications
Lab Testing
Key references
Disclosed Labs