Neboglamine
CR-2249 / nebostinel
Neboglamine (CR-2249 / nebostinel) is a cognitive & mood research compound. Positive allosteric modulator of the glycine site on the NMDA receptor — it enhances NMDA signaling without directly agonizing it, which theoretically avoids excitotoxicity.
Neboglamine quick facts
| Reported research dose | 60mg-120mg |
| Route | Oral |
| Frequency | Not established — no dosing protocol has been characterized |
| Half-life | Not established in humans |
| Forms | Oral |
| Evidence level | Trialed as a schizophrenia adjunct then discontinued; no efficacy data published |
Very early and very thin. The allosteric approach is a sound idea and the compound simply never produced results worth publishing. There is no dosing guidance here because none exists — anyone quoting one is inventing it.
How Neboglamine works
Positive allosteric modulator of the glycine site on the NMDA receptor — it enhances NMDA signaling without directly agonizing it, which theoretically avoids excitotoxicity.
Proposed benefits
Researched for focus, memory, neuroprotection, mood and stress resilience.
Where to get Neboglamine
Buy Neboglamine at Disguised Alpha →The evidence for Neboglamine
Graded by what exists behind each claim.
✅ Clinically validated
- Reached phase 2 as a potential adjunct treatment for schizophrenia. Development did not continue, and detailed results were not widely published — an outcome that leaves the compound in an unusually undefined state for something that reached that stage.
📊 Correlative data
- Essentially no community use, and no published series. The absence is worth stating: unlike most compounds here there is no anecdotal layer, so there is very little to weigh in either direction.
🧪 Theoretical / extrapolated
- A positive allosteric modulator of the glycine site on the NMDA receptor — it makes the receptor more responsive to glycine rather than activating it directly.
- NMDA hypofunction is a long-standing hypothesis in schizophrenia, and allosteric modulation is the safer way to address it: it enhances existing signaling rather than forcing it, which limits excitotoxic risk.
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 Neboglamine actually does
Neboglamine is not a peptide, a racetam or a piperazine. It is an amino acid derivative: (4S)-4-amino-5-[(4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid, C13H24N2O3, molecular weight 256.34 National Center for Biotechnology Information 2026. Read the name and the parentage is obvious — it is L-glutamic acid with its alpha-carboxyl converted to an amide of 4,4-dimethylcyclohexylamine, leaving the side-chain carboxylic acid and the alpha-amino group free. The papers that characterized it call it exactly that: a compound selected from a series of glutamic acid derivatives Garofalo 1996 Lanza 1997.
The target is the glycine co-agonist site of the NMDA receptor, and the pharmacology is unusually precisely defined. Lanza 1997 measured NMDA-evoked release of [3H]noradrenaline from rat hippocampal slices and asked a sharp question: does this compound change glycine's potency or its efficacy? The answer was efficacy only. Glycine's EC50 of 21.5 ± 4.2 µM was not significantly changed, while the size of the glycine effect was enhanced in a concentration-dependent manner at 3, 10 and 30 µM of neboglamine. It also increased [3H]MK-801 binding concentration-dependently, and showed positive cooperativity with glycine.
That combination has a specific meaning. A competitive ligand at the glycine site would shift glycine's EC50. This does not. Positive cooperativity with glycine, plus enhanced open-channel blocker binding, plus unchanged potency, is the signature of a ligand acting at a separate allosteric site that increases the receptor's responsiveness to whatever glycine is already there — which is precisely what Lanza 1997's authors conclude. It is the safer half of the NMDA-hypofunction hypothesis in schizophrenia: you amplify existing signaling rather than forcing it, so the effect is self-limiting when the co-agonist site saturates.
And there is a chemistry problem that nobody in this literature addresses. The computed topological polar surface area is 92.4 Å2 and XLogP is −1.3 National Center for Biotechnology Information 2026. Both numbers sit firmly on the wrong side of the usual rules of thumb for passive blood-brain barrier penetration, which want a TPSA below roughly 60–70 and a positive logP. This molecule carries a free carboxylic acid and a free primary amine — it is a zwitterion at blood pH, and zwitterions do not diffuse through membranes. Yet Chiusaroli 2010 reports that oral neboglamine produced dose-dependent central effects in rats. The reconciliation almost certainly involves an amino acid transporter — the route L-DOPA, gabapentin and baclofen all use — but no published study has identified a transporter for this molecule. Its own delivery mechanism is unexplained.
Cell, rodent, human — and where it stops
Step one, rat hippocampal slices. Concentration-dependent enhancement of glycine efficacy at 3, 10 and 30 µM, glycine EC50 unchanged at 21.5 µM, increased MK-801 binding, positive cooperativity Lanza 1997. Hold the 3–30 µM range; it is the only quantitative concentration this compound has.
Step two, rodent behavior, and one detail is more informative than the headline. Garofalo 1996 showed CR 2249 reversing scopolamine-induced memory deficit in rat step-through passive avoidance and electroconvulsive-shock-induced deficit in mouse step-down passive avoidance, and improving performance in animals with no cholinergic deficit — so it is not simply an anticholinergic antidote. General behavior and motor activity were unchanged, ruling out a sensorimotor artifact. The detail that matters: it was active only when given 45 minutes before training, and did nothing when given immediately after training or before the retention trial. That is an acquisition drug, not a consolidation or retrieval drug, and it constrains the mechanism far more than a positive result alone would. Microdialysis in freely moving rats found increased hippocampal noradrenaline release with reduced 3,4-dihydroxyphenylglycol efflux, which led the authors to a noradrenergic hypothesis that the later NMDA work partly supersedes.
Step three, the antipsychotic-model study, which is the strongest work on this compound. Chiusaroli 2010 compared neboglamine with D-serine, clozapine and haloperidol in rats. Fos-like immunoreactivity — a marker of neuronal activation — rose with neboglamine by 3.2-fold in prefrontal cortex, 4.8-fold in nucleus accumbens and 4.5-fold in lateral septal nucleus. In the dorsolateral striatum, haloperidol raised it 390-fold and neboglamine and clozapine had no effect at all. That contrast is the entire extrapyramidal-side-effect story in one measurement. Neboglamine's activation pattern closely matched D-serine's, the endogenous glycine-site agonist, which is exactly what the receptor pharmacology predicts. It restored NMDA-mediated neurotransmitter release in frontal cortex punches exposed to phencyclidine, and oral neboglamine dose-dependently inhibited PCP-induced hyperlocomotion and rearing — while, unlike haloperidol and clozapine, not affecting basal locomotor activity. An antipsychotic-like effect without sedation is a genuinely unusual profile.
Step four, humans: a phase 2 program in schizophrenia that produced no published results. There is no indexed randomized trial of neboglamine, no published efficacy data, no published human pharmacokinetics and no published safety database. A search of the literature for a neboglamine schizophrenia trial returns nothing. Development stopped, and whether it stopped for futility, for safety or for commercial reasons is not in the public record.
The obstacle, and it is a concentration-and-delivery obstacle. The only effect concentration is 3–30 µM in a slice bath Lanza 1997. Take the 60–120 mg doses in circulation: 60 mg of a 256.34 g/mol compound is about 234 µmol, and if it distributes into extracellular water — which is what a zwitterion with TPSA 92.4 does National Center for Biotechnology Information 2026 — say 0.25 to 0.6 L/kg in a 70 kg person, the plasma concentration lands somewhere around 5 to 13 µM. That is squarely inside the range that worked in the slice, which is a rarer piece of good news than it sounds. But the slice bath concentration is the concentration at the receptor, and the brain concentration of a molecule that cannot cross a membrane passively is not the plasma concentration. Without a transporter identified and without a single measurement of brain or cerebrospinal-fluid exposure, the arithmetic gets you to the door and no further.
Neboglamine pharmacokinetics — how much of it actually gets in
There is no published human pharmacokinetic study of neboglamine, and no animal one either. What can be said comes from the structure and from the routes used in the rodent work.
What the structure predicts, and it is not encouraging for passive delivery. XLogP −1.3, TPSA 92.4 Å2, a free carboxylic acid and a free primary amine National Center for Biotechnology Information 2026. At blood pH the molecule is a zwitterion. That predicts low passive membrane permeability, poor passive oral bioavailability, negligible first-pass metabolism because there is little to metabolize, and a small volume of distribution confined close to extracellular water. Compounds shaped like this are normally absorbed and delivered by amino acid transporters rather than by diffusion.
What degrades it: probably very little, and that is the point. There is no ester to hydrolyze and no obvious site for a cytochrome P450 to attack except the dimethylcyclohexyl ring. The most likely fate of a glutamate-derived amide is amidase hydrolysis back to glutamic acid and 4,4-dimethylcyclohexylamine, or renal excretion of the intact zwitterion by an organic anion or amino acid transporter. Neither has been demonstrated. No metabolite has been identified in any species.
The numbers that do exist. Effect concentrations of 3, 10 and 30 µM in rat hippocampal slices Lanza 1997; a glycine EC50 of 21.5 µM as the yardstick; oral dosing producing dose-dependent behavioral effects in rats Chiusaroli 2010; and behavioral activity in Garofalo 1996 requiring administration 45 minutes before training, which implies absorption and central distribution inside that window. The rodent work in this series used systemic administration, including intraperitoneal injection, and the fact that the oral route also worked is the strongest indirect evidence that a transporter is carrying it.
What follows for a person. The site's card says the half-life has never been established in humans, and that is exactly right — it has not been established in any species. The 60–120 mg doses in circulation are not derived from a human dose-finding study, because none was published; the arithmetic in the translation section shows they land in a plausible plasma range, which is a coincidence worth noting and not a validation.
What would have to be true, and how you would know it was not
Three predictions. The first two are what would distinguish this compound from an antipsychotic, and the third argues against expecting much from it.
1. Prolactin should not move, and that is a real prediction rather than an absence of one. Every drug that works on psychosis through D2 blockade raises prolactin, because D2 receptors on lactotrophs are what holds prolactin down. Neboglamine has no D2 action — Chiusaroli 2010 found zero Fos activation in the dorsolateral striatum where haloperidol produced a 390-fold rise. So draw prolactin at baseline and at 6 weeks and expect it flat. If prolactin rises, either the product is not neboglamine or the mechanism is not what three papers say it is, and given an unregulated supply of a compound with no commercial manufacturer, the first explanation is the likelier one.
2. The cognitive effect, if any, should be on acquisition and should be acute. Garofalo 1996 found activity only when dosed 45 minutes before training, and nothing when dosed after training or before retention. That is a specific, testable claim: run a paired-associate learning task and Trail Making A and B 45–90 minutes after a dose, and again on a control day. Learning new material should improve; recalling material learned before the dose should not. Very few nootropic claims are this precise, and this one comes straight out of the animal design.
3. The prediction that cuts against it: nothing should happen in a healthy person, and that is what the mechanism implies. Neboglamine amplifies glycine's efficacy at a site glycine already occupies Lanza 1997, and in a normally functioning glutamatergic system that site is largely saturated. Every positive rodent result was obtained in a deficit model — scopolamine amnesia, electroconvulsive shock, phencyclidine-induced NMDA hypofunction Garofalo 1996 Chiusaroli 2010. A drug that restores impaired signaling has nothing to restore in an unimpaired brain. So the honest expectation for a healthy user is no detectable effect, and a clear subjective effect in a healthy person is more likely to indicate a mislabeled product than a mechanism the literature describes. Pair the cognitive testing with a Comprehensive Metabolic Panel (CMP) at baseline and 8 weeks, because a compound with no published human safety data deserves at least a liver and kidney check.
What nobody has tested yet
The phase 2 results were never published, and that absence is itself the most important unknown. A compound that reaches phase 2 has, by definition, accumulated phase 1 human safety and pharmacokinetic data. That data exists somewhere. None of it is in the public literature: no half-life, no Cmax, no dose-proportionality, no adverse event table. Anyone quoting a dose for this compound is quoting a number whose provenance cannot be checked, and the single most valuable thing that could happen to this page is publication of the phase 1 dossier.
Nobody has identified how it gets into the brain. A zwitterion with TPSA 92.4 and XLogP −1.3 National Center for Biotechnology Information 2026 should not cross the blood-brain barrier passively, and yet oral dosing produced central effects in rats Chiusaroli 2010. The experiment is standard: transfected cell lines expressing LAT1, LAT2 and the relevant amino acid transporters, with uptake measured against known substrates. If neboglamine is an LAT1 substrate, that explains delivery and predicts a competition interaction with dietary large neutral amino acids — which would mean a protein-rich meal changes the dose reaching the brain. That is a practical consequence nobody has looked for.
Nobody has run the acquisition-versus-consolidation experiment in a human. Garofalo 1996's timing result is a strong, unusual, and cheap prediction to test: dose before learning versus immediately after learning, same task, same people, crossover. It would either reproduce the animal finding in a person or show that it does not transfer, and either answer would be the first human cognitive data this compound has.
And nobody has tested it in the population it was designed for. Chiusaroli 2010's conclusion was explicitly to support clinical evaluation in schizophrenia, on the strength of a Fos activation pattern matching D-serine's and antipsychotic-like behavior without the striatal activation that predicts extrapyramidal side effects. Sixteen years later there is no published trial. The glycine-site hypothesis in schizophrenia remains live and this is one of the few compounds ever built specifically for it.
Neboglamine — its own safety story, not its class's
There is no human safety data in the public record for this compound. No published phase 1, no adverse event table, no toxicology, no chronic dosing study, no case report. The class safety block on this page covers phenibut, trazodone, propranolol and cabergoline — drugs with defined receptor liabilities that neboglamine does not share. None of it applies here.
The mechanism-based argument for relative safety is genuine, and it should be understood rather than trusted. A positive allosteric modulator at a co-agonist site can only amplify signaling that is already happening, and it runs out of effect when the site saturates — Lanza 1997 showed neboglamine raising glycine's efficacy without shifting its EC50, which is the pharmacological signature of exactly that ceiling. Compare with direct NMDA agonism, which has no ceiling and is the classic route to excitotoxicity. That is a real structural safety advantage over the alternative approach to the same hypothesis. It is not a substitute for a toxicology package, and no toxicology package has been published.
The one clean negative finding worth stating. Chiusaroli 2010 found that, unlike haloperidol and clozapine, neboglamine did not affect basal locomotor activity, and produced no Fos activation in the dorsolateral striatum where haloperidol produced a 390-fold increase. In rodent terms that predicts no sedation and no extrapyramidal liability. It is a meaningful negative result from a well-designed comparison, and it is the best safety evidence this molecule has.
What the missing dose-finding study means in practice. The 60–120 mg figures in circulation were not established by any published human study. The arithmetic in this page's translation section suggests they may land in a plausible plasma range, which is reassuring only in the sense that they are not obviously absurd. There is no published maximum tolerated dose, no ceiling and no reported overdose experience, so there is no basis on which to judge whether more would be harmful or merely useless.
And the honest bottom line. This is a compound with a well-characterized receptor mechanism, three good preclinical papers, a coherent rationale in schizophrenia, and zero published human results of any kind despite having been given to humans. That specific combination — extensive preclinical work and an unpublished clinical program — is the least informative state a molecule can be in, because the data that would settle it exists and is not available. Nothing on this page should be read as suggesting the absence of published harm is evidence of safety.
Sources read for this page
- 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
- Garofalo P, Colombo S, Lanza M. CR 2249: a new putative memory enhancer. Behavioural studies on learning and memory in rats and mice.. J Pharm Pharmacol 1996 · PMID 9004193
- Chiusaroli R, Garofalo P, Espinoza S. Antipsychotic-like effects of the N-methyl-D-aspartate receptor modulator neboglamine: an immunohistochemical and behavioural study in the rat.. Pharmacol Res 2010 · PMID 20045056
- National Center for Biotechnology Information. PubChem Compound Summary for CID 3074827, Neboglamine.. PubChem, retrieved 2026
Neboglamine — 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 group acts directly on established CNS receptors — GABA-B (phenibut), serotonergic and histaminergic (trazodone, doxepin), beta-adrenergic (propranolol), dopaminergic (cabergoline, apomorphine). These are pharmacological drugs, not research peptides, and the predicted problems are the known ones for each receptor.
- Phenibut is the one that needs saying plainly: it is physically addictive. GABA-B agonism produces tolerance within days of regular use, and withdrawal is genuinely severe — anxiety, insomnia, tremor, and in heavy users, psychosis and seizures. It is closer to a benzodiazepine than to a nootropic in this respect, and it is sold as though it were the latter.
- Propranolol blunts the physical symptoms of adrenaline. That predicts the useful effect and also the problem — it blunts the training response and masks hypoglycemia.
- Dopamine agonists predict nausea, orthostatic hypotension and, at the doses used in Parkinson's, impulse-control problems. Cabergoline's half-life is very long, so effects persist well past a dose.
What has actually been reported
- Phenibut dependence and withdrawal are well documented in case reports and poison-center data.
- Trazodone: sedation, orthostatic hypotension, and rarely priapism — which is a medical emergency.
- Abrupt propranolol cessation causes rebound tachycardia and hypertension. Do not stop a beta-blocker suddenly.
- Cabergoline at high cumulative doses is associated with cardiac valve changes; at the low doses used for prolactin this has not been shown.
How to reduce the risk
Same mechanism as the prediction.
- For phenibut, the only reliable mitigation is frequency: occasional use does not produce dependence, regular use does. There is no dose that makes daily use safe.
- Taper anything in this group rather than stopping abruptly.
- Take the first dose of anything with orthostatic effects at home, sitting down.
What it does to your bloodwork
A fact about the assay.
- Prolactin if using cabergoline (it is usually why you are). Otherwise blood pressure and heart rate are the monitoring that matters.
Don't run this if
- You already take a sedative, a benzodiazepine, or drink regularly — the CNS depressant effects are additive and this is where respiratory depression comes from.
- You are on an antidepressant and considering trazodone — serotonergic combinations need a prescriber, not a forum.
The honest unknown
- Most of this group is well characterized for its licensed use. What is NOT characterized is the off-label use most people here are making of it, at doses and durations nobody studied.
Not medical advice. If you take prescription medication or have a diagnosed condition, check this with a pharmacist or doctor.
Neboglamine — interference & stacking
Predicted from mechanism, not from an interaction study. How mechanism-predicted claims are made →
What Neboglamine 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 — Neboglamine in an order, with the rest of what you're running.
Unlock in Skool — $10/mo →Bloodwork to run alongside Neboglamine
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
Neboglamine — frequently asked questions
What is Neboglamine?
Neboglamine (CR-2249 / nebostinel) is a cognitive & mood research compound. Positive allosteric modulator of the glycine site on the NMDA receptor — it enhances NMDA signaling without directly agonizing it, which theoretically avoids excitotoxicity.
Is the full Neboglamine protocol on this page?
The reported research dose is on this page, along with how Neboglamine 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 Neboglamine?
Neboglamine has an approximate half-life of Not established in humans, which is part of what determines how often it's dosed.
What's the evidence behind Neboglamine?
Current evidence level: Trialed as a schizophrenia adjunct then discontinued; no efficacy data published. Neboglamine is offered for research purposes only and is not an approved medicine.
What Neboglamine is used for
Neboglamine 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.