Quick Comparison
| Coluracetam | Sunifiram | |
|---|---|---|
| Half-Life | 2-3 hours | Estimated 1-2 hours (limited data) |
| Typical Dosage | Standard: 20-80 mg sublingually, 2-3 times daily. Start at 20 mg to assess sensitivity. Sublingual is strongly preferred for bioavailability. | 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 | Sublingual (strongly preferred) or oral. Oral bioavailability is limited. | Sublingual (preferred) or oral. Very small doses — requires a milligram scale for accurate dosing. |
| Research Papers | 1 papers | 10 papers |
| Categories |
Mechanism of Action
Coluracetam
Coluracetam's primary mechanism is enhancement of high-affinity choline uptake (HACU) in hippocampal neurons — the rate-limiting step in acetylcholine synthesis. HACU is mediated by the high-affinity choline transporter (CHT1/SLC5A7), which coluracetam upregulates or potentiates, increasing the Vmax of choline transport into presynaptic terminals. By making this process more efficient, coluracetam increases acetylcholine production and vesicular packaging via the vesicular acetylcholine transporter (VAChT) even when choline levels are normal. This enhances cholinergic transmission in the hippocampus, cortex, and retina — explaining reports of enhanced color vision and visual acuity. Coluracetam also has minor AMPA receptor positive allosteric modulation. The compound was studied for treatment-resistant depression, possibly through cholinergic modulation of mood circuits.
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
Coluracetam
Common
Headache, fatigue, brain fog at high doses.
Serious
Very limited human safety data — studied only in small trials.
Rare
Anxiety, irritability, suicidal ideation was reported in one clinical trial participant.
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
Coluracetam →
A racetam that enhances high-affinity choline uptake (HACU) — the rate-limiting step in acetylcholine synthesis. This makes it uniquely effective at boosting acetylcholine levels, which is why users commonly report enhanced color vision, sharper visual perception, and improved memory. It was briefly studied for treatment-resistant depression.
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.