Sunifiram
DM-235
Sunifiram (DM-235) is a cognitive & mood research compound. Piperazine-derived ampakine — positive modulation of AMPA receptors, with downstream NMDA and acetylcholine effects. Reported as roughly 1,000× more potent than piracetam by weight in rodent models.
Sunifiram quick facts
| Reported research dose | 5–10mg (research) |
| Route | Oral |
| Frequency | 1–2x · Sparingly |
| Half-life | Short; effects reported at 1–3 hours |
| Forms | Oral |
| Evidence level | Rodent memory models only — no human data whatsoever |
The potency figure people quote is a rodent finding, not a human one, and it's the reason the doses are in single milligrams. ⚠️ Ampakines carry a theoretical excitotoxicity risk with chronic use, and there is no human safety data at all. Headaches and overstimulation are the common anecdotal complaints.
How Sunifiram works
Piperazine-derived ampakine — positive modulation of AMPA receptors, with downstream NMDA and acetylcholine effects. Reported as roughly 1,000× more potent than piracetam by weight in rodent models.
Proposed benefits
Researched for focus, memory, neuroprotection, mood and stress resilience.
Where to get Sunifiram
Buy Sunifiram at Disguised Alpha →The evidence for Sunifiram
Graded by what exists behind each claim.
Human clinical evidence
- No human trials: development stopped at preclinical, so the ceiling on any claim here is a rodent model — and these transfer poorly.
📊 Correlative data
- Community use at very small doses. Reported experience is of a sharp acute effect on focus, with a short duration. The safety record is community reports only — there is no toxicology in humans at all, which for a glutamatergic compound is a meaningful gap.
🧪 How the mechanism reads
- A piperazine derivative, structurally unrelated to the racetams despite being grouped with them. Rodent work suggests AMPA receptor potentiation and cholinergic activity at roughly a thousand times piracetam's potency.
- Ampakine potency is a double-edged mechanism: strong AMPA potentiation is the same pharmacology that raises excitotoxicity concerns, and no one has characterized where that line sits in humans.
Why an empty tier is not a verdict →
How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →
What Sunifiram actually does
Sunifiram is not a racetam and it does not contain a pyrrolidone ring. It is 1-(4-benzoylpiperazin-1-yl)propan-1-one — a piperazine with a benzoyl group on one nitrogen and a propanoyl on the other — C14H18N2O2, molecular weight 246.30, computed XLogP 1.1, topological polar surface area 40.6 Å2 National Center for Biotechnology Information 2026. Those last two numbers are the reason it works at all by mouth: a TPSA under about 60 and a logP near 1–3 is the classic profile of a molecule that crosses the blood-brain barrier easily.
Here is a fact worth knowing before you buy any of it. Nefiracetam is also C14H18N2O2 with a molecular weight of 246.30 National Center for Biotechnology Information 2026. Same formula, same mass, completely different scaffold — nefiracetam is an anilide of a pyrrolidone, sunifiram a diacylpiperazine. They are constitutional isomers. A certificate of analysis reporting a mass of 246.3 cannot tell them apart, and the appropriate dose differs by a factor of about thirty. Only a nuclear magnetic resonance spectrum or a chromatographic retention time against a reference standard distinguishes them.
What the receptor pharmacology actually says, and it is not what the label “ampakine” implies. Romanelli 2006 is explicit and it is the most important sentence in this compound's literature: unifiram and sunifiram do not show affinity in binding studies for the most important central receptors or channels. No measured Ki at AMPA, at NMDA, at nicotinic or muscarinic receptors, at any of them. Every mechanistic statement about this molecule is therefore functional inference — drug in, effect out, blocked by antagonist X — rather than a binding constant.
The functional evidence points at the glycine co-agonist site of the NMDA receptor, not at AMPA. Moriguchi 2013 did the electrophysiology in mouse hippocampal slices. Sunifiram at 10–100 nM enhanced NMDA-receptor-dependent long-term potentiation in the CA1 region, and the enhancement was abolished by 7-chlorokynurenic acid, an antagonist at the glycine site, but not by ifenprodil, which blocks the polyamine site. Pretreating the slice with a saturating 300 µM glycine abolished the effect entirely — if the site is already fully occupied, sunifiram has nothing left to do. That is as close to a competition experiment as a functional study gets, and it localizes the action to the glycine site.
Downstream, the signaling is specified. The LTP enhancement ran through PKC-alpha phosphorylation of the NMDA receptor and CaMKII phosphorylation of the AMPA receptor, with Src family kinase upstream — the Src inhibitor PP2 blocked it Moriguchi 2013. So AMPA receptor phosphorylation is a consequence, two kinases downstream, not the drug's target. That is why calling this an ampakine, as most sources do, gets the pharmacology one receptor out of order. The earlier work is not contradicted — Galeotti 2003 showed both compounds reversing amnesia caused by the AMPA antagonist NBQX at 30 mg/kg, and reversing kynurenate's block of NMDA-mediated noradrenaline release in rat hippocampal slices — but the two findings fit together best with the glycine site upstream and AMPA downstream.
And the dose-response is bell-shaped, which changes everything. The LTP effect peaked at 10 nM and was smaller at 100 nM Moriguchi 2013; PKC-alpha and Src activation followed the same inverted-U with the same 10 nM peak. A bell-shaped curve means more is worse past the peak, and it is the single most practically important property of this molecule.
Cell, rodent, human — and where it stops
Step one, mouse behavior, and the potency claim comes from here. Ghelardini 2002 used the mouse passive avoidance test against scopolamine-induced amnesia (scopolamine 1.5 mg/kg intraperitoneally). DM235 prevented the amnesia at 0.001–0.1 mg/kg by intraperitoneal injection and 0.01–0.1 mg/kg orally — an effect comparable to piracetam at 30–100 mg/kg, aniracetam at 100 mg/kg or rolipram at 30 mg/kg. It also reversed amnesia induced by mecamylamine, baclofen and clonidine, which is a broad set of mechanisms to be effective against. In rats it prevented scopolamine-induced impairment in the Morris water maze at 0.1 mg/kg, and at the highest effective doses it did not impair rotarod performance or change spontaneous motility. The paper's own summary is that its potency is about 1,000 times higher than the most active piracetam-like compounds.
A discrepancy worth flagging, because both numbers get quoted. Ghelardini 2002 says about 1,000-fold. Romanelli 2006, from the same group four years later, says four orders of magnitude — 10,000-fold. Ten-fold disagreement between two papers by overlapping authors about their own compound. Neither figure is a measured potency ratio from a shared assay; both are comparisons of minimum effective doses across different experiments, which is the weakest form of potency comparison there is.
Step two, rat hippocampal slices. Galeotti 2003 showed both compounds reversing kynurenic acid's antagonism of NMDA-mediated [3H]noradrenaline release, with the reversal itself abolished by NBQX; Romanelli 2006 adds that they increase acetylcholine release from rat cerebral cortex.
Step three, mouse hippocampal slices with quantitative electrophysiology. Moriguchi 2013: LTP enhancement over 10–100 nM, peak at 10 nM, field EPSP slope rising dose-dependently over 1–1000 nM, glycine-site localization, PKC-alpha/CaMKII/Src signaling.
Step four, humans: nothing. Zero. No trial of any phase, no pharmacokinetic study, no toxicology in any species that has been published, no case series.
The obstacle, stated as arithmetic rather than as an attitude. Two numbers have to be put beside each other and almost nobody does it. The effective concentration is 10 nM at the peak of an inverted-U Moriguchi 2013; at 246.3 g/mol that is about 2.5 ng/mL. The dose in common use is 5–10 mg. Assume a volume of distribution of 1 L/kg — a reasonable estimate for a small neutral molecule with XLogP 1.1 National Center for Biotechnology Information 2026, and an assumption, because nobody has measured it — and 5 mg in a 70 kg person gives roughly 70 ng/mL, about 290 nM. That is nearly thirty times the concentration at which the effect peaked and beyond the top of the range that was tested for LTP at all. Even 1 mg lands near 58 nM. On the only quantitative pharmacology this compound has, the doses people take sit on the far side of a bell-shaped curve. The rodent doses tell the same story: scaling 0.1 mg/kg in a mouse by body surface area gives roughly 0.6 mg for a 70 kg human, not 5–10 mg.
Sunifiram pharmacokinetics — how much of it actually gets in
No human pharmacokinetic study of sunifiram exists, and no animal one has been published either. No half-life, no clearance, no volume of distribution, no metabolite identification. This section is what can be bounded from structure and from the dosing routes used in the animal work, and it is labeled as inference.
What the structure predicts. Molecular weight 246.30, XLogP 1.1, TPSA 40.6 Å2 National Center for Biotechnology Information 2026. Small, neutral, moderately lipophilic and with low polar surface area: that combination predicts good passive absorption and easy blood-brain barrier penetration, and it is consistent with Ghelardini 2002 finding oral doses effective at only ten times the intraperitoneal injection dose — a small oral penalty implying oral bioavailability is decent rather than negligible.
What degrades it, reasoned from the two bonds that matter. The molecule is a di-amide: a benzamide and a propanamide, both on piperazine nitrogens. Tertiary amides are relatively stable to plasma esterases and to simple hydrolysis, so the likely route is hepatic oxidation — a cytochrome P450 attacking the propanoyl chain or the aromatic ring, followed by conjugation. Which cytochrome has never been determined, which means no interaction can be predicted and none can be excluded.
The duration people report is 1 to 3 hours, which for a 246 Da compound cleared by hepatic oxidation is entirely plausible and is the one piece of the picture where anecdote and chemistry agree. But note what a short half-life does to a bell-shaped dose-response: after a single dose the blood concentration sweeps down through the effective window. If the peak concentration overshoots the 10 nM optimum Moriguchi 2013, the best part of the experience arrives on the way down, an hour or two after the dose — which is exactly the pattern of report this compound generates, and it is a testable prediction rather than a rationalization.
What would have to be true, and how you would know it was not
Three predictions. The first is the one that argues against the way the compound is used.
1. The prediction that cuts against it: a smaller dose should work better than a larger one. This follows directly from the inverted-U in Moriguchi 2013, where 10 nM beat 100 nM. Run it within one person: 1 mg, 3 mg and 10 mg on separate days, in randomized order, with Trail Making A and B and a digit-span task at 60 and 150 minutes after each. If performance is best at the lowest dose, the bell-shaped curve transfers and the standard 5–10 mg dosing is wrong. If performance rises monotonically with dose, then the slice pharmacology does not describe what is happening in a person and the mechanistic story on this page needs rewriting. Either answer is worth having and the experiment costs three afternoons.
2. The effect should be acute and should not build. Every positive finding in this literature is a single-dose effect — one administration 20 minutes before training Ghelardini 2002, or a slice perfused for minutes Moriguchi 2013. Nothing predicts accumulation. So a MoCA at baseline and after four weeks of intermittent use should show nothing beyond a practice effect, while the acute measurement in prediction 1 should show something on day one. A compound that only “works after a few weeks” is behaving unlike anything in its own literature.
3. The safety read-out, because a glutamatergic compound with zero toxicology deserves one. A Comprehensive Metabolic Panel (CMP) at baseline and 8 weeks. There is no published toxicology for sunifiram in any species, so this is not monitoring a known signal — it is establishing that the liver and kidney are unchanged in a compound where nobody has ever looked. Expected result: no change. Any change is new information, and it is information nobody currently has.
And one purity check that is not a blood test. Because sunifiram and nefiracetam share the formula C14H18N2O2 and the mass 246.30 National Center for Biotechnology Information 2026 National Center for Biotechnology Information 2026, a mass-only certificate proves nothing. Ask for NMR or an HPLC retention time against a reference standard. Taking 5 mg of a compound that is dosed at 5 mg is reasonable; taking 5 mg of a compound that is dosed at 200 mg is a wasted month.
What nobody has tested yet
Nobody has ever measured a binding constant for this molecule. Romanelli 2006 states plainly that no affinity was found for the major central receptors and channels, and twenty years later that gap is unfilled. The specific missing experiment is now obvious from Moriguchi 2013: run sunifiram against [3H]glycine or [3H]MK-801 binding at the NMDA receptor complex, the way Lanza 1997 did for a different glycine-site modulator, and find out whether it binds the site its functional pharmacology points at. Until somebody does, the mechanism is inference from blockade experiments.
Nobody has published a pharmacokinetic study in any species. Not one. The 10 nM optimum Moriguchi 2013 cannot be connected to any dose in any animal, let alone a person, and every dose-response argument on this page — including the one that says the human doses are far too high — rests on an assumed volume of distribution. A single-dose rat PK study with plasma and brain concentrations at six time points would convert that assumption into a number and would tell everyone using this compound whether they are at 10 nM or at 300.
Nobody has tested the inverted-U in a whole animal. The bell-shaped curve is a slice result. A four-dose behavioral study in mice spanning 0.001 to 1 mg/kg — the range Ghelardini 2002 already partly covered — measuring both behavior and brain concentration would establish whether the inverted-U survives in vivo, which is the difference between “take less” being a real recommendation and being a slice artifact.
And there is no toxicology at all. No repeat-dose study, no genotoxicity, no reproductive toxicity, in any species. For a compound acting on the NMDA receptor complex — where both excessive activation and excessive blockade have well-documented consequences — a 28-day rodent repeat-dose study is the cheapest, most basic, most conspicuously missing piece of work attached to this molecule.
Sunifiram — its own safety story, not its class's
The honest starting point: there is no safety data for sunifiram in humans or in animals. No published toxicology, no trial, no adverse event database, no chronic dosing study in any species. The class safety block on this page is about cholinergics and dopaminergics; this compound is neither.
The mechanism-based concern is specific and it is not the usual one. Sunifiram's functional target is the glycine co-agonist site of the NMDA receptor Moriguchi 2013, and it acts as a positive modulator there. Excessive NMDA receptor activation is the canonical route to excitotoxicity, and it is the reason direct NMDA agonists were never developed as drugs. Positive allosteric modulation at a co-agonist site is genuinely gentler than direct agonism — it can only amplify signaling that is already occurring, and it saturates when the site fills, which is why the 300 µM glycine experiment abolished the effect. That is a real safety argument. It is not the same as a safety finding, and nobody has run the experiment that would produce one.
The dose problem is the practical hazard. The only quantitative concentration-response for this molecule is bell-shaped with a peak at 10 nM Moriguchi 2013, and the arithmetic in the pharmacokinetics section puts a 5 mg oral dose in the region of 290 nM. Nobody knows what sustained exposure at thirty times the optimum does, because nobody has measured anything above 1000 nM in any preparation. The two most common anecdotal complaints — headache and overstimulation — are what you would expect on the far side of an inverted-U, and the response that follows from the pharmacology is to reduce the dose rather than to add choline.
Product identity is a safety issue for this compound specifically. Sunifiram and nefiracetam are isomers sharing the formula C14H18N2O2 and a mass of 246.30 National Center for Biotechnology Information 2026 National Center for Biotechnology Information 2026, and they are dosed roughly thirty-fold apart. A mislabeled powder taken at the wrong scale is the most likely bad outcome here, and it is invisible to the mass-spectrometry certificate most vendors provide.
What can honestly be said in the compound's favor. Ghelardini 2002 reported no impairment of motor coordination on the rotarod and no change in spontaneous motility or exploratory behavior at the highest effective doses, and reduced the duration of pentobarbitone hypnosis at 1 mg/kg without changing its onset. Those are real negative safety observations in mice, at doses on the order of a thousandth of what a person takes per kilogram. They are the best safety evidence this compound has, and stating that plainly is more useful than either reassurance or alarm.
Sources read for this page
- Ghelardini C, Galeotti N, Gualtieri F. DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer.. Naunyn Schmiedebergs Arch Pharmacol 2002 · PMID 12070754
- Galeotti N, Ghelardini C, Pittaluga A. AMPA-receptor activation is involved in the antiamnesic effect of DM 232 (unifiram) and DM 235 (sunifiram).. Naunyn Schmiedebergs Arch Pharmacol 2003 · PMID 14600801
- Romanelli MN, Galeotti N, Ghelardini C. Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancers.. CNS Drug Rev 2006 · PMID 16834757
- Moriguchi S, Tanaka T, Narahashi T. Novel nootropic drug sunifiram enhances hippocampal synaptic efficacy via glycine-binding site of N-methyl-D-aspartate receptor.. Hippocampus 2013 · PMID 23733502
- Lanza M, Bonnafous C, Colombo S. Characterization of a novel putative cognition enhancer mediating facilitation of glycine effect on strychnine-resistant sites coupled to NMDA receptor complex.. Neuropharmacology 1997 · PMID 9294970
- National Center for Biotechnology Information. PubChem Compound Summary for CID 4223812, Sunifiram.. PubChem, retrieved 2026
- National Center for Biotechnology Information. PubChem Compound Summary for CID 71157, Nefiracetam.. PubChem, retrieved 2026
Sunifiram — safety, predicted from mechanism
Predicted from mechanism, not from a human safety trial. How that reasoning works →
What the mechanism predicts
Derived from the molecule, not a trial.
- This class is broad, but the predicted problems cluster by mechanism rather than by molecule. Cholinergics (racetams, and anything raising acetylcholine) predict headache — the classic one, from choline demand outrunning supply. Dopaminergics and eugeroics predict tolerance, sleep disruption and a flat mood on the days off. Anything glutamatergic or AMPA-facing carries a theoretical excitotoxicity concern at high doses.
- The pattern worth internalizing: anything that borrows performance from tomorrow eventually presents the bill. Sleep is the most common currency it gets paid in.
What has actually been reported
- Headache is the most reported effect across the racetam family and usually responds to added choline.
- Irritability, blunted affect and a rebound low on cessation are commonly reported with the stimulant-adjacent members.
- Most of this class has little or no controlled human safety data at the doses actually used.
How to reduce the risk
Same mechanism as the prediction.
- Take a choline source with any racetam. The headache is the mechanism running out of substrate, and it is largely preventable rather than something to push through.
- Dose in the morning. Almost everything in this class has a longer functional tail than its half-life suggests, and sleep is the first thing you lose.
- Use them for something, not as a habit. The compounds that carry tolerance genuinely reward intermittent use aimed at a task, and genuinely punish daily use aimed at feeling normal.
- One at a time, and long enough to judge it. This is the class where people stack five and cannot tell you which one is doing anything — and the effects are subjective, so attribution is already hard enough.
- If you need it to feel normal, stop. That is the line where a tool has become a dependency, and it is the one worth watching for.
What it does to your bloodwork
A fact about the assay.
- No routine marker tracks these. Sleep is the assay — if it is degrading, the compound is costing more than it is producing, and that shows up before anything else does.
Don't run this if
- A seizure history — several of these lower the threshold at least theoretically, and it is not worth establishing empirically.
- Bipolar disorder, for the dopaminergic members especially.
- Alongside prescribed psychiatric medication without knowing exactly how the mechanisms overlap.
The honest unknown
- Chronic use is essentially uncharacterized. The specific unmeasured thing is what daily cholinergic or dopaminergic pressure does to baseline function over years — not whether a few weeks is tolerable.
Not medical advice. If you take prescription medication or have a diagnosed condition, check this with a pharmacist or doctor.
Sunifiram — interference & stacking
Predicted from mechanism, not from an interaction study. How mechanism-predicted claims are made →
What Sunifiram moves on your bloodwork
Expected direction, not a measured one.
- Comprehensive Metabolic Panel (CMP) — ◆ worth watching
Most of this class has no predicted marker movement at all, and saying so is more useful than listing markers that will not move.
What to do: A baseline liver panel is reasonable for anything taken daily and long-term. Beyond that there is nothing specific to chase.
- How to work up to it, and when not to
- When to take it, and why that window
- Cycle length
- Time off between cycles
- Fasted or fed, and when in the day
- Coach Cam's personal notes
- Which compounds push the same lever, and why the dose adds up faster than people count
- What blunts it — the stacks that waste your money
- What compounds the risk, so a side effect arrives sooner than any one of them suggests
- Coach Cam's read on running it alongside the rest of your protocol
Everything above is free and stays free. Skool is where it becomes a plan — Sunifiram in an order, with the rest of what you're running.
Unlock in Skool — $10/mo →Bloodwork to run alongside Sunifiram
Baseline first, then again at 8–12 weeks.
| Marker | What it’s watching for |
|---|---|
| TSH (Thyroid-Stimulating Hormone) | Thyroid disease imitates every cognitive complaint there is |
| Vitamin B12 | Deficiency causes fog long before it causes anemia |
| Methylmalonic Acid (MMA) | Catches the deficiency a normal B12 hides |
| Ferritin | Low iron flattens cognition at levels most labs call fine |
| Vitamin D (25-Hydroxy) | Commonly low, cheap to correct, associated with mood |
The Brain Fog & Cognition panel covers these in one order — 12 markers, $233.06 with the discount applied.
Check results you already have → · All 103 markers A–Z
Sunifiram — frequently asked questions
What is Sunifiram?
Sunifiram (DM-235) is a cognitive & mood research compound. Piperazine-derived ampakine — positive modulation of AMPA receptors, with downstream NMDA and acetylcholine effects. Reported as roughly 1,000× more potent than piracetam by weight in rodent models.
Is the full Sunifiram protocol on this page?
The reported research dose is on this page, along with how Sunifiram works and the evidence behind it. The protocol — how to work up to it, frequency, cycle length, time off, what not to stack it with and Coach Cam's notes — is inside Skool.
What is the half-life of Sunifiram?
Sunifiram has an approximate half-life of Short; effects reported at 1–3 hours, which is part of what determines how often it's dosed.
What's the evidence behind Sunifiram?
Current evidence level: Rodent memory models only — no human data whatsoever. Sunifiram is offered for research purposes only and is not an approved medicine.
What Sunifiram is used for
Sunifiram appears under 1 goal in the goal router.
Related Cognitive & Mood compounds
Where this goes next
The pages here are the frameworks. The protocols — the dosing, the order to correct things in, the week-by-week schedule and what to retest — are inside Skool.