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Surface here is educational only; do not use without medical supervision. Our editorial verdict is SKIP-FOR-NOW — current cost / risk / redundancy puts it below the line.
Neboglamine
Italian-origin (Rottapharm) glutamic-acid-derived positive allosteric modulator at an allosteric site of the NMDA glycine co-agonist…
Aliases (5)
Overview
What is Neboglamine?
Neboglamine (CR-2249) is a positive allosteric modulator of the NMDA receptor glycine binding site, originally developed by Rotta Pharmaceuticals as an investigational antipsychotic and cognitive enhancer for schizophrenia.
Key Benefits
Investigated for treating negative and cognitive symptoms of schizophrenia, where NMDA hypofunction is implicated. Reported pro-cognitive effects on memory and attention without the receptor desensitization typical of orthosteric NMDA agonists.
Mechanism of Action
Selective positive allosteric modulator at the glycine B (strychnine-insensitive) site of the NMDA receptor, enhancing glutamate-driven receptor activation only when glutamate is bound, providing activity-dependent NMDA potentiation.
Pharmacokinetics
▸Brand options4 known
Status"Investigational worldwide. Not scheduled. Not approved by FDA, EMA, PMDA. Highest reached: Phase 2 (schizophrenia, cocaine dependence) under Rottapharm SpA — last public registry update 2010; no Phase 3 program; status appears stalled rather than formally discontinued."
Research Indications
Facilitates glycine action
increases [³H]MK-801 binding (an open-channel marker of NMDA activation) in a concentration-dependent manner, with positive cooperativity…
Reverses kynurenic acid antagonism
kynurenic acid is the endogenous tryptophan-pathway metabolite that *antagonizes* the glycine site (and the α7 nicotinic receptor), and K…
Activity-dependent
PAM behavior means it requires endogenous glycine to do anything. With no glycine around, neboglamine alone does nothing at the receptor.…
In rats, neboglamine increased FLI (Fos-like immunoreactivity) in prefrontal cortex similarly to haloperidol and clozapine
the antipsychotic-overlap behavioral signal that motivated the schizophrenia program (Pubmed 20045056, Drago/Caccia/Spada 2010).
Weak NRI activity at supratherapeutic exposures (>100 mg)
at clinical doses (25-75 mg) this is not the dominant mechanism; at higher research-chem doses it would contribute and add a stimulant-fl…
Plasma half-life ~4 hours
reported short, requiring multi-daily dosing for sustained NMDA-tone elevation.
Research Protocols
Disclaimer: These are commonly discussed research protocols and not medical advice.
Peptide Interactions
same direction, but the whole point of a PAM over an agonist is that you don't *need* to load the agonist binding partner. Stacking would be redundant and wo…
orthogonal mechanism (DAT/NET inhibition + histaminergic + orexinergic). No formal data. Sequential layering (establish modafinil baseline first) is the only…
the encyclopedia's pre-existing flag stands. Two unproven glutamate-system amplifiers (AMPA PAM + NMDA glycine PAM) at the same time multiplies unknowns and …
directly opposing on the NMDA axis (memantine = uncompetitive NMDA channel blocker; neboglamine = NMDA potentiator at the glycine co-agonist site). They don'…
agmatine is a modest GluN2B-preferring NMDA antagonist + nNOS modulator. Same opposing-direction logic as memantine, weaker in absolute effect. For trial cle…
all NMDA antagonists; opposing direction; do not run together.
same-direction glutamate-system enhancers via different mechanisms. Stacking is mechanistically pointless and additively risky.
additive cortical excitability / theoretical seizure-threshold issues. Not relevant for the canonical stack but worth flagging.
mechanism overlap; no point and adds risk.
NOW Foods Glycine 3 g/day in the canonical stack is a borderline case — at oral 3 g, plasma glycine rises modestly, but synaptic glycine is heavily reuptake-…
Quality Indicators
Pharmacy-dispensed, intact packaging
Prescription tablets in original sealed packaging from a licensed pharmacy.
Generic vs branded
Generics are usually fine but bioavailability can vary slightly; track if you switch.
Unbranded blister or counterfeit risk
Counterfeit pharmaceuticals are a known issue; verify pharmacy and lot if buying internationally.
What to Expect
- Day 1PK-driven acute peak per administration. Verify dose tolerated.
- Week 1Steady-state reached for most daily-dosed pharma.
- Week 2-4Therapeutic effect established; titration window if needed.
- Long-termPeriodic monitoring per drug class (labs, BP, ECG as applicable).
Side Effects & Safety
Common (>10% in trials): Not reported above placebo at clinical doses in published Phase 1 summaries. Granular AE rates are not in the public domain — interpret with caution.
Less common (1-10%): Headache, mild nausea, occasional dizziness reported at higher doses in unsourced biohacker accounts. Insomnia possible if dosed late given the NRI activity at higher exposures.
Rare-serious / theoretical (<1% but worth knowing):
- Excitotoxicity / seizure threshold: theoretical concern shared with all glycine-site enhancers. Activity-dependent PAM mechanism should limit risk vs direct agonists, but no human seizure data exists in healthy long-term use. Combined with subconcussive impact load (the canonical archetype), this is the most material risk.
- Pro-psychotic in vulnerable individuals: NMDA agonism/PAM action can theoretically destabilize people with prodromal psychosis or strong family-history risk. Schizophrenia trial population was already-diagnosed and on adjunctive antipsychotic; healthy-adult risk window is not characterized.
- Sleep disruption: NRI activity at higher doses + cortical-excitability angle = unfavorable for late-evening dosing.
- Long-term safety: zero data beyond Phase 2 short-duration windows. Chronic NMDA-glycine-site potentiation has no human safety record beyond ~weeks-to-months in trial-grade settings. Receptor-system adaptation, spine-density changes, plasticity rebound on discontinuation — all theoretical and untested.
- Drug development "stall" implication: when a Phase 2 program goes quiet for 10+ years without formal discontinuation announcement, the most parsimonious explanation is a failed efficacy or unfavorable risk/benefit signal that the sponsor chose not to publish. This is not provable from public data, but it is a real Bayesian concern.
Specific watch periods for any pilot:
- Days 1-3 (single-dose tolerability): acute headache, nausea, dizziness, any aura-flavored phenomena, BP spike, sleep onset.
- Days 4-10 (chronic tone): mood drift (low or high), anxiety, irritability, sleep architecture changes.
- Discontinuation Days 1-7: rebound watch — no published taper data, no withdrawal syndrome characterized, but plasticity-system rebound is the theoretical concern.
References
Neboglamine — Wikipedia
basic mechanism + Phase 2 status snapshot (last meaningful update 2015).
View StudySynapse Patsnap — Neboglamine drug page
registry-tier development status; lists schizophrenia as currently active, Alzheimer's/MDD/cocaine as inactive.
View StudyNCATS Inxight Drugs — Neboglamine
UNII 12EA34U5B8; FDA-side database entry confirming sponsor/mechanism.
View StudyLanza et al., 1996 — *Pharmacol Biochem Behav* — CR 2249 memory enhancer
passive avoidance learning rodent paradigm; original cognitive-enhancement paper.
View StudyLanza et al., 1997 — *Neuropharmacology* — characterization of glycine-site PAM mechanism
kynurenate reversal, MK-801 binding cooperativity; foundational pharmacology.
View StudyLanza et al., 1997 — *CNS Drug Reviews* — "Cognition Enhancing Profile of CR 2249"
review-tier summary of preclinical cognition profile.
View StudyDrago et al., 2010 — *Pharmacol Res* — Antipsychotic-like effects of NMDA modulator neboglamine
rat antipsychotic-overlap (FLI in PFC) behavioral study.
View StudyPatent CA2567397C — Use of neboglamine (CR 2249) as antipsychotic and neuroprotective
Rottapharm IP basis for schizophrenia indication.
View StudyPatent EP1755583B1 — Use of neboglamine for treatment of schizophrenia (Rottapharm)
schizophrenia-specific patent.
View StudyPatent EP1940376A2 — Use of neboglamine in toxicodependency
IP basis for cocaine/morphine dependence indication.
View StudyStone et al., 1995 — *Eur J Pharmacol* — Putative cognition enhancers reverse kynurenic acid antagonism at hippocampal NMDAs
broader category mechanism (D-cycloserine, glycine, D-serine, aniracetam) reversing KYNA antagonism.
View StudyPothakos et al., 2018 — *Front Pharmacol* — Glycine modulatory site of NMDA targeting in schizophrenia
review of glycine-site approaches; comparator framing for neboglamine vs other classes.
View StudyPenchant Research Library — Neboglamine compound entry
secondary aggregator (lists "phase 1" — flagged as less accurate than AdisInsight/Synapse "phase 2").
View StudyInvivoChem — Neboglamine product page
research-supplier listing, mechanism summary (note: describes as "glycine-associated agonist" — less precise than PAM-at-distinct-site).
View StudyUmbrella Labs — Neboglamine HCl product page
consumer-facing research-chem source: $59.99/g, ≥99% LC-MS COA dated 2025-12-05; multiple formats (powder/liquid/capsule).
View StudyBenchChem — Neboglamine product page (CAS 163000-63-3)
research-supplier listing.
View StudyTargetMol / AbMole / GlpBio / MedChemExpress — Neboglamine HCl listings (CAS 2759182-59-5)
lab-grade research suppliers.
View StudyPubChem — Neboglamine (CID 3074827)
chemical structure, formula, identifiers.
View StudyEPA CompTox — Neboglamine chemical details
environmental/regulatory chemical reference.
View StudyHow was your experience with this compound?
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