Nefiracetam
GABA + AMPA + Ca-channel modulator racetam, anti-amnestic.
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Pharmacology
Contents
WHAT IS NEFIRACETAM?
Detailed overview
Nefiracetam (DM-9384) is a Daiichi Pharmaceutical development built on the Piracetam scaffold with a dimethyl-phenyl-acetyl substituent. It acts at several sites: nicotinic + muscarinic ACh receptor positive modulation (PMID 10869513), NMDA receptor glycine-site modulation (PMID 17095583), sustained opening of L- and N-type voltage-gated Ca²⁺ channels (PMID 10850736), and PKA/PKC signaling cascade amplification (PMID 9443926). Ca²⁺-channel modulation is the primary anti-amnestic mechanism. Anti-excitotoxic profile (protects neurons from glutamate-induced damage). Phase 3 trials (post-stroke apathy, Alzheimer`s) ran in Japan; the NIH USA Phase 2 Alzheimer`s trial was halted over a male-hepatotoxicity signal.
Mechanism
GABA-A + AMPA + L-Ca²⁺
Half-life
~3-5 h
Legal status
Investigational, not approved
Receptor profile
- Nicotinic ACh receptors (PKCα)Moderate
- GABA-A receptorsModerate
- L-type calcium channelsModerate
- Serotonin / norepinephrineModerate
Safety
Side effects, stop signs, contraindications
Side effects · 6
- Headache, often from increased cholinergic activity (may be eased by choline supplementation)
- Nausea and mild gastrointestinal discomfort
- Irritability, restlessness or anxiety, especially at higher doses
- Fatigue, brain fog or sluggishness (GABA-A facilitation)
- Sleep disturbance, vivid dreams (cholinergic effect)
- Dizziness and transient drops in concentration
Contraindications · 5
- Liver impairment or elevated liver enzymes: the US Phase 2 trial was halted over a male hepatotoxicity signal, so avoid in hepatic disease
- Pregnancy and breastfeeding: no human safety data, avoid given animal toxicity concerns
- Preclinical toxicology showed testicular toxicity at high doses, so long-term high-dose use is not advised
- Not approved anywhere, a clinical research compound: unknown long-term human safety, not recommended without medical supervision
- Use caution when combined with cholinergic or GABAergic agents and sedatives (additive effects)
Related Nootropics
Same therapeutic category
FAQ
FAQ
Nefiracetam is a Japanese-developed racetam compound that acts on several brain signaling systems at once (GABA, AMPA, calcium channels), and it has mainly been studied as an anti-amnestic, meaning a substance meant to counter memory impairment. The available information here is at the basic-research level, no well-documented human-use results are included in the source. So it's best viewed as a research curiosity rather than an established supplement.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.