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 Nefiracetam and NSI-189 — mechanism, side effects, legal status, and pricing.
Nefiracetam is a non-peptide small molecule in the racetam (pyrrolidinone/2-oxopyrrolidine acetamide) class, investigated as a cognitive enhancer. It was never approved by the FDA, EMA, or Japan's PMDA; Daiichi Seiyaku withdrew its Japanese NDA (Translon) in February 2002 after a repeat Phase III trial in dementia failed to demonstrate efficacy. A US/Canada Phase II trial in poststroke depression (600 mg and 900 mg/day) showed no overall separation from placebo, though a subgroup analysis suggested benefit in the most severely depressed patients at 900 mg. No validated therapeutic dose or approved indication exists; it is sold by research-chemical and laboratory-reagent suppliers for research use only.
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.
Nefiracetam
NSI-189
Category
Legal Status
Mechanism
Side Effects
COA-verified vendors · trust score ≥70 required · single-vial price — bulk/bundle deals may be lower
Nefiracetam
No pricing data yet.
Check Nefiracetam prices →NSI-189
No pricing data yet.
Check NSI-189 prices →COA corpus from Disclosed Labs — independently tested batches only.
Nefiracetam
2
COAs
99.6%
Avg purity
2
Labs
NSI-189
No COA data yet.
Submit testing data →Human clinical data are limited and largely negative or mixed. Japanese Phase II/III trials in dementia/cognitive sequelae after cerebrovascular disorders showed improvement over placebo in some early trials, but a Ministry of Health-mandated repeat Phase III trial under revised guidelines failed to demonstrate efficacy, and Daiichi Seiyaku withdrew its Japanese NDA (Translon) in February 2002. A US/Canada multicenter randomized double-blind Phase II trial (28 sites, 1999–2001, n=159) tested nefiracetam 600 mg and 900 mg/day vs. placebo for poststroke depression; the drug did not separate from placebo overall (response >70%, remission >40% in both arms) but showed significant benefit in the most-severely-depressed subgroup at 900 mg (Robinson et al., J Neuropsychiatry Clin Neurosci 2008). A related post hoc analysis examined apathy outcomes in the same cohort. Preclinical findings include: rat cortical neurons showed potentiation of native α4β2-type nicotinic acetylcholine receptor currents via a G(s)-protein-dependent pathway; rat dorsal root ganglion neurons showed dual concentration-dependent effects on GABA_A receptor-channel currents mediated via cAMP-dependent protein kinase and Gi/Go proteins; rat neuronal preparations showed enhancement of high-voltage-activated N/L-type Ca²⁺ channel currents and modulation of NMDA receptor function via PKC-dependent phosphorylation; rat passive avoidance models showed reversal of apomorphine-induced amnesia and preservation of hippocampal NCAM-mediated memory consolidation during scopolamine disruption.
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.
Nefiracetam 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