Quick Comparison
| Alpha-GPC | Sunifiram | |
|---|---|---|
| Half-Life | 4-6 hours | Estimated 1-2 hours (limited data) |
| Typical Dosage | Standard: 300-600 mg daily in 1-2 doses. For racetam stacking: 300 mg per racetam dose. Clinical (Alzheimer's): 1200 mg daily in 3 divided doses. | 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 (capsules, powder). High oral bioavailability. | Sublingual (preferred) or oral. Very small doses — requires a milligram scale for accurate dosing. |
| Research Papers | 10 papers | 10 papers |
| Categories |
Mechanism of Action
Alpha-GPC
Alpha-GPC (L-alpha-glycerylphosphorylcholine) is hydrolyzed by phospholipases in the gut and brain to release free choline, which is transported across the blood-brain barrier via the choline transporter (CHT1) and taken up by neurons for acetylcholine synthesis via choline acetyltransferase (ChAT). It is the most efficient oral choline source for raising brain acetylcholine levels due to high bioavailability and direct utilization. Alpha-GPC also provides glycerophosphate (glycerol-3-phosphate), which enters the Kennedy pathway and supports phosphatidylcholine and cell membrane phospholipid synthesis. It may stimulate growth hormone release through cholinergic activation of the pituitary. Alpha-GPC enhances high-affinity choline uptake and supports muscarinic (M1, M2) and nicotinic receptor function.
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
Alpha-GPC
Common
Headache, heartburn, dizziness, skin rash.
Serious
High chronic doses may be associated with increased stroke risk (epidemiological data, not confirmed causally).
Rare
Fishy body odor from trimethylamine production, depression.
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
Alpha-GPC →
The most bioavailable choline source for the brain. Alpha-GPC crosses the blood-brain barrier efficiently and directly provides choline for acetylcholine synthesis. Used clinically in Europe for Alzheimer's disease and cognitive decline. The go-to choline supplement for stacking with racetams and preventing the headaches that come from increased acetylcholine demand.
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.