Quick Comparison
| Fasoracetam | Sunifiram | |
|---|---|---|
| Half-Life | 1.5-2.5 hours | Estimated 1-2 hours (limited data) |
| Typical Dosage | Standard: 20-100 mg sublingually or orally, 1-3 times daily. Many users find 20-40 mg effective. Clinical trials for ADHD used 100-400 mg twice daily. | Standard: 4-8 mg sublingually. Active doses are very small — do NOT dose by weight equivalence with piracetam. Start at 4 mg. Do not use daily due to lack of long-term data. Sublingual preferred for consistent absorption. |
| Administration | Oral or sublingual. Sublingual may provide better absorption. | Sublingual (preferred) or oral. Very small doses — requires a milligram scale for accurate dosing. |
| Research Papers | 5 papers | 10 papers |
| Categories |
Mechanism of Action
Fasoracetam
Fasoracetam upregulates GABA-B receptor (GABA-B1/GABA-B2 heterodimer) expression and function, which is unique among racetams — this receptor upregulation is potentially beneficial for restoring GABAergic sensitivity after prolonged benzodiazepine or phenibut use. It enhances group II metabotropic glutamate receptor (mGluR2/mGluR3) signaling, which modulates presynaptic glutamate release and reduces excitotoxicity. Fasoracetam increases acetylcholine release in the cerebral cortex via modulation of choline acetyltransferase activity and vesicular acetylcholine transporter function. It may also modulate the glutamatergic system through mGluR5. The combination of GABAergic (GABA-B-mediated inhibition), glutamatergic (mGluR modulation), and cholinergic enhancement provides anxiolytic effects alongside cognitive enhancement. Clinical trials focus on ADHD patients with GRM (glutamate receptor) gene variants.
Sunifiram
Sunifiram (DM-235) is a positive allosteric modulator of AMPA receptors (GluA1-4 subunits) — an ampakine that slows receptor desensitization and deactivation, enhancing glutamatergic excitatory neurotransmission and calcium influx through the receptor. This calcium influx activates CaMKII (calcium/calmodulin-dependent protein kinase II), which phosphorylates GluA1 at Ser831 and is a key enzyme in long-term potentiation (LTP) and memory consolidation. Sunifiram also activates protein kinase C (PKC) isoforms, which phosphorylate GluA2 and regulate receptor trafficking. It increases acetylcholine release in the prefrontal cortex and hippocampus, likely via presynaptic nicotinic receptor activation or enhanced glutamatergic drive onto cholinergic neurons. Downstream, these mechanisms enhance CREB phosphorylation, Arc expression, and synaptic AMPA receptor insertion — the molecular basis of memory formation.
Risks & Safety
Fasoracetam
Common
Headache, fatigue, mild digestive discomfort.
Serious
Limited long-term human safety data.
Rare
Low mood, brain fog, loss of motivation at very high doses.
Sunifiram
Common
Overstimulation, headache, jaw clenching at higher doses.
Serious
No long-term human safety data. Animal studies show a wide therapeutic index.
Rare
Insomnia, anxiety, irritability.
Full Profiles
Fasoracetam →
A newer racetam that uniquely upregulates GABA-B receptors, making it potentially useful for people who have developed tolerance to GABAergic substances like Phenibut or benzodiazepines. It also enhances glutamate and acetylcholine signaling. Being studied in clinical trials for ADHD in adolescents with specific glutamate receptor gene mutations.
Sunifiram →
An experimental ampakine compound structurally related to piracetam but estimated to be 1,000x more potent. Sunifiram enhances AMPA receptor function, increases long-term potentiation in the hippocampus, and activates CaMKII and PKC signaling — molecular processes directly involved in memory formation. It has a noticeable acute effect on focus and memory, but very limited human safety data.