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.
Dosage
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.
Dosages shown are for research reference only. Always consult a qualified healthcare provider.
Half-Life
Estimated 1-2 hours (limited data)
Administration
Sublingual (preferred) or oral. Very small doses — requires a milligram scale for accurate dosing.
Shop Sunifiram
99%+ purity · third-party lab tested
Mechanism of Action
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.
Regulatory Status
Research compound. Not approved or regulated by any agency. Not a controlled substance. Limited commercial availability.
Risks & Safety
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.
Compare Sunifiram With
Research Papers
10Published: December 28, 2022
AI Summary
Moreover, the carbamate hybrid 3f was found to exhibit higher in vitro potency than donepezil with IC50 = 18 ± 0.2 nM, 29.9 ± 0.15 nM for 3f and donepezil, respectively. 3f was also found to effectively inhibit AChE activity in rat brain (AChE = 1.
Published: July 12, 2006
AI Summary
These compounds are able to increase the release of acetylcholine from rat cerebral cortex, and, as far as unifiram is concerned, to increase the amplitude of fEPSP in rat hippocampal slices. In vitro experiments, performed on hippocampal slices, also supported the hypothesis of a role of the AMPA receptors for the cognition-enhancing properties...
Published: March 31, 2016
AI Summary
This paper is a review of the work of my former academic group of research in the past 15 years, in the field of cognition enhancers (also called nootropics) that identified two very potent molecules: Unifiram and Sunifiram that for a variety of reasons were not protected by a patent. Some 12 years
Published: June 14, 2002
AI Summary
At the highest effective doses, the investigated compound neither impaired motor coordination (rota-rod test), nor modified spontaneous motility and inspection activity (Animex and hole board tests). These results indicate that DM235, a compound structurally related to piracetam, is a novel nootropic endowed with the capability to prevent cognit...
Published: October 15, 2013
AI Summary
In mouse hippocampal slices, sunifiram at 10-100 nM significantly enhanced LTP in a bell-shaped dose-response relationship which peaked at 10 nM. The LTP enhancement by sunifiram was significantly inhibited by PP2, a Src family inhibitor.
Published: March 31, 2013
AI Summary
The spatial reference memory assessed by Y-maze and short-term memory assessed by novel object recognition task were significantly improved by sunifiram treatment in OBX mice. Stimulation of CaMKII and PKC autophosphorylation by sunifiram was significantly inhibited by pre-treatment with gavestinel.
Published: October 31, 2009
AI Summary
A series of amides and sulfonamides, structurally related to DM235 (sunifiram) and MN19 (sapunifiram), derived by ring expansion or contraction, or by inversion of the exocyclic amide function, have been synthesized and tested for cognition-enhancing activity in the mouse passive-avoidance test. Som
Published: January 1, 2004
AI Summary
An interesting result of this research is the identification of two compounds (13 and 14) that are endowed with amnesing activity (the opposite of the activity of the original molecules) and are nearly equipotent to scopolamine.
Published: November 30, 2008
AI Summary
A series of amides, structurally related to DM232 (unifiram) and DM235 (sunifiram), characterized by a 1,2,3,4-tetrahydropyrazino[2,1-a]isoindol-6(2H)-one, 1,4-diamino-cyclohexane or 1,4-diaminobenzene ring, have been synthesized and tested for cognition-enhancing activity in the mouse passive-avoid
Published: January 31, 2008
AI Summary
The compounds display minimal effective doses in the range 0.3-10mg/kg. Although the new substances do not show improved activity when compared to the parent compounds, some useful information has been obtained to understand structure-activity relationships.
Frequently Asked Questions
What is Sunifiram used for?
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.
What are the side effects of 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.
How is Sunifiram administered?
Sunifiram is administered via sublingual (preferred) or oral. very small doses — requires a milligram scale for accurate dosing..
What is the half-life of Sunifiram?
The half-life of Sunifiram is Estimated 1-2 hours (limited data).
Related Nootropics
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.
Aniracetam
A fat-soluble racetam roughly 5-10x more potent than Piracetam by weight. Known for its anxiolytic (anti-anxiety) properties alongside cognitive enhancement — a combination that makes it popular for social situations and creative work. It modulates both glutamate and dopamine/serotonin systems, giving it a unique mood-lifting quality that other racetams lack.
CDP-Choline
Also known as Citicoline, this is a naturally occurring compound that provides both choline and cytidine (which converts to uridine in the body). This dual action supports both acetylcholine synthesis and cell membrane repair, making it both a cognitive enhancer and a neuroprotectant. Prescribed in many countries for stroke recovery and cognitive decline.
Citicoline (CDP-Choline)
A naturally occurring intermediate in the synthesis of phosphatidylcholine, the primary phospholipid in neuronal cell membranes. Citicoline provides both choline (for acetylcholine and phospholipid synthesis) and cytidine (converted to uridine, supporting RNA and synapse formation). It is prescribed in Europe and Japan for stroke recovery and cognitive decline. Cognizin is the most studied branded form.
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.
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.