Informational only. Not medical advice.INFORMATIONAL PLATFORM ONLY — NOT MEDICAL ADVICE, DIAGNOSIS, OR TREATMENT
Head-to-head comparison of Nefiracetam and Oxiracetam — 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.
Oxiracetam is a non-peptide racetam-class cognitive enhancer, structurally the 4-hydroxy analog of piracetam. It is approved as a prescription drug for dementia in Italy (since 1984) and China, but is NOT FDA-approved in the United States. The FDA has classified oxiracetam as a 'new drug' requiring approval and determined it does not qualify as a dietary supplement; in the US it is sold only as an unregulated gray-market research chemical.
Nefiracetam
Oxiracetam
Category
Legal Status
Mechanism
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Nefiracetam
No pricing data yet.
Check Nefiracetam prices →Oxiracetam
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Check Oxiracetam prices →COA corpus from Disclosed Labs — independently tested batches only.
Nefiracetam
2
COAs
99.6%
Avg purity
2
Labs
Oxiracetam
2
COAs
99.4%
Avg purity
2
Labs
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.
Multiple placebo-controlled human trials exist in dementia, organic brain syndrome, and traumatic brain injury populations, plus human pharmacokinetic studies. One double-blind controlled trial in elderly organic-brain-syndrome patients used doses titrated from 400–2400 mg/day; a separate placebo-controlled trial in senile dementia of Alzheimer type and multi-infarct dementia used 800 mg twice daily and reported improvement on cognitive measures versus placebo. Preclinical findings include AMPA receptor modulation and enhanced neurotransmitter release in rat hippocampal preparations, and identification of the (S)-enantiomer as the active component alleviating cognitive impairment in a rat chronic cerebral hypoperfusion model. Oral bioavailability in humans is ~56% (versus 28–42% in rats, 81–90% in dogs), with predominantly renal excretion of unchanged drug.
Nefiracetam and Oxiracetam 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.
Side Effects
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Lab Testing
Key references