Quick Comparison

CDP-CholineSunifiram
Half-Life56-71 hours (long elimination half-life)Estimated 1-2 hours (limited data)
Typical DosageStandard: 250-500 mg daily in 1-2 doses. Clinical (stroke/cognitive decline): 500-2000 mg daily. Most nootropic users find 250-500 mg sufficient.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.
AdministrationOral (capsules, tablets). Very well-absorbed with nearly 100% oral bioavailability.Sublingual (preferred) or oral. Very small doses — requires a milligram scale for accurate dosing.
Research Papers10 papers10 papers
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Mechanism of Action

CDP-Choline

CDP-Choline is hydrolyzed by nucleotidases and phosphatases into choline and cytidine after oral ingestion. Choline enters the acetylcholine synthesis pathway via choline acetyltransferase. Cytidine is phosphorylated to CTP and converted to uridine monophosphate (UMP), which enters the Kennedy pathway and stimulates the synthesis of phosphatidylcholine via the enzyme CTP:phosphocholine cytidylyltransferase — phosphatidylcholine is a critical component of neuronal cell membranes and synaptic vesicles. This dual mechanism simultaneously boosts neurotransmitter production and repairs membrane damage from oxidative stress or ischemia. CDP-Choline also increases dopamine D2 receptor density in the striatum and enhances dopamine release. It may modulate glutamate excitotoxicity and support mitochondrial 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

CDP-Choline

Common

Headache, nausea, diarrhea, insomnia.

Serious

Very safe — extensive clinical safety data.

Rare

Blurred vision, chest pain, allergic reactions.

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.

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