Supplement
Sunifiram is a lab-made compound, related to the racetam family, that appears to boost signaling through glutamate receptors, which are central to learning and memory. Its best-supported finding is in rodents, where memory loss induced by a drug was less severe in maze and avoidance tests, at roughly 1,000 times the potency of piracetam. Still, the evidence is very limited: it comes entirely from animal and lab work, and no human studies exist.
Sources: PMID 14600801; PMID 12070754
- Updated
- How we grade
- 4 studies cited
- Best evidence
- Grade D
- Conditions studied
- 1
- Outcomes
- 4
- Graded outcomes
- 0004
Evidence by condition
- Strong
- Moderate
- Limited
- Very limited
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Memory Protection (Anti-Amnesic Effects) In rodent models, sunifiram (0.001-0.1 mg/kg) reversed scopolamine-induced amnesia in mouse passive avoidance tests and rat Morris water maze tests, with potency approximately 1,000 times greater than piracetam. It also reversed amnesia induced by the AMPA receptor antagonist NBQX. No human studies exist. | Improves (the measure goes up) | Moderate effect | 3 studies | |||
Studies that measured memory protection (anti-amnesic effects) | ||||||
General
| Grade | Outcome | Effect | Size | Studies | People | Studies list |
|---|---|---|---|---|---|---|
| Synaptic Plasticity (Long-Term Potentiation) In mouse hippocampal slices, sunifiram (10 nM) significantly enhanced long-term potentiation (LTP) via the glycine-binding site of NMDA receptors in a bell-shaped dose-response relationship. It also enhanced excitatory synaptic transmission in rat hippocampal slices. All data is from in vitro preparations with no human confirmation. | Improves (the measure goes up) | Moderate effect | 2 studies | |||
Studies that measured synaptic plasticity (long-term potentiation) | ||||||
| AMPA Receptor Activation In rodent models and hippocampal slice preparations, sunifiram's antiamnesic effects were shown to operate through activation of the AMPA-mediated neurotransmission system. Additionally, sunifiram activated CaMKII signaling and increased phosphorylation of both AMPA and NMDA receptors. All evidence is preclinical. | Improves (the measure goes up) | Moderate effect | 2 studies | |||
| Acetylcholine Release In rat cerebral cortex tissue preparations, sunifiram increased acetylcholine release, a mechanism associated with cognitive enhancement. This finding is from a single in vitro pharmacological characterization study with no human replication. | Improves (the measure goes up) | Small effect | 1 study | |||
Studies that measured acetylcholine release | ||||||
Key findings
- Memory Protection (Anti-Amnesic Effects)Improves (the measure goes up)
- Synaptic Plasticity (Long-Term Potentiation)Improves (the measure goes up)
- AMPA Receptor ActivationImproves (the measure goes up)
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- Grade D
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Studies cited
4 studies from PubMed
- Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine-binding site of N-methyl-D-aspartate receptor
- Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancers
- AMPA-receptor activation is involved in the antiamnesic effect of DM 232 (unifiram) and DM 235 (sunifiram)
- DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer