SPAGLUMIC ACID

Possibly Marketed Outside US

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H16N2O8
Molecular Weight	304.2533
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)N[C@@H](CC(=O)N[C@@H](CCC(O)=O)C(O)=O)C(O)=O

InChI

InChIKey=GUCKKCMJTSNWCU-BQBZGAKWSA-N

InChI=1S/C11H16N2O8/c1-5(14)12-7(11(20)21)4-8(15)13-6(10(18)19)2-3-9(16)17/h6-7H,2-4H2,1H3,(H,12,14)(H,13,15)(H,16,17)(H,18,19)(H,20,21)/t6-,7-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C11H16N2O8
Molecular Weight	304.2533
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9202308 | https://www.ncbi.nlm.nih.gov/pubmed/10899918 | https://www.drugbank.ca/drugs/DB08835

Spaglumic acid (NAAG) is the β-aspartyl isoform of N-Acetyl-l-aspartylglutamate (isospaglumic Acid is N-(N-Acetyl-l-α-aspartyl)-l-glutamic acid). In eye drops, spaglumic acid is either a magnesium or sodium salt of N-Acetyl-l-aspartylglutamate. Spaglumic acid is a mast cell stabilizer. Thus it is used in allergic conditions such as allergic conjunctivitis. Specifically spaglumic acid is approved in Portugal under the brand name Naabak and in Greece under the brand name Naaxia for use in patients with allergic conjunctivitis. Spaglumic Acid is a peptide neurotransmitter and the third-most-prevalent neurotransmitter in the mammalian nervous system. It is a weak activator of NMDA receptors and a highly selective agonist for mGlu3 receptors. Spaglumic Acid is neuroprotective under non-hydrolysing conditions in vivo.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Metabotropic glutamate receptor 3 16 Target ID: CHEMBL3067 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9202308	Agonist 2752		19.0 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Conjunctivitis 17 Sources: https://www.healthician.org/showthread.php?4431-NAAXIA-Acetyl-aspartyl-glutamic-acid-Dosage-Side-Effects-Pregnancy https://www.ncbi.nlm.nih.gov/pubmed/9395007	Primary		Approved 8583	Naaxia Approved Use Indication: Anti-allergic eye drops with no preservatives. It is the treatment for eye infections (conjunctivitis, blepharoconjunctivitis).

Doses

Dose	Population	Adverse events
60 mg 3 times / day multiple, respiratory Highest studied dose Dose: 60 mg, 3 times / day Route: respiratory Route: multiple Dose: 60 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2757885/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2757885/	Sources: https://pubmed.ncbi.nlm.nih.gov/2757885/
4.9 % 6 times / day multiple, topical Recommended Dose: 4.9 %, 6 times / day Route: topical Route: multiple Dose: 4.9 %, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9226074/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9226074/	Disc. AE: Contact allergy... AEs leading to discontinuation/dose reduction: Contact allergy Sources: https://pubmed.ncbi.nlm.nih.gov/9226074/

AEs

AE	Significance	Dose	Population
Contact allergy	Disc. AE	4.9 % 6 times / day multiple, topical Recommended Dose: 4.9 %, 6 times / day Route: topical Route: multiple Dose: 4.9 %, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9226074/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/9226074/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
activator 150 inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OATP1B3 961 OATP1B1 1079 CYP1A2 2153 CYP2C19 2057

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/188803#section=BioAssay-Results Page: 5.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/188803#section=BioAssay-Results Page: 21.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/188803#section=BioAssay-Results Page: 17.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/188803#section=BioAssay-Results Page: 22.0	no
CYP3A4 2633	activator 342 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/188803#section=BioAssay-Results Page: 17.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/188803#section=BioAssay-Results Page: 17.0	no
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxMDU2MTYifX0=	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIxMDU2MTYifX0=	yes [Inhibition 10 uM]

PubMed

Title	Date	PubMed
Using proton magnetic resonance imaging and spectroscopy to understand brain "activation".	2007-08	16935326
Modulation of GABAergic inhibition in the rat superior colliculus by a presynaptic group II metabotropic glutamate receptor.	2006-12-01	16973709
Effects of NAAG peptidase inhibitor 2-PMPA in model chronic pain - relation to brain concentration.	2006-12	16926034
Ketamine and N-acetylaspartylglutamate peptidase inhibitor exert analgesia in bone cancer pain.	2006-09	16960267
Regulation of N-acetylaspartate and N-acetylaspartylglutamate biosynthesis by protein kinase activators.	2006-09	16945114
Metabolic analysis of mouse brains that have compromised iron storage.	2006-09	16855871
[Alteration of the antinociceptive systems in chronic daily headaches].	2006-08-31	16941423
Identifying the affected hemisphere by (1)H-MR spectroscopy in patients with temporal lobe epilepsy and no pathological findings in high resolution MRI.	2006-05	16722973
NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat.	2006-05	16606367
NAAG peptidase as a therapeutic target: Potential for regulating the link between glucose metabolism and cognition.	2006-04	16804566
ProFit: two-dimensional prior-knowledge fitting of J-resolved spectra.	2006-04	16541464
Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer.	2006-03-22	16467855
Neurotransmitters of the suprachiasmatic nuclei.	2006-02-16	16480518
Differential negative coupling of type 3 metabotropic glutamate receptor to cyclic GMP levels in neurons and astrocytes.	2006-02	16417588
Metabolite changes in early relapsing-remitting multiple sclerosis. A two year follow-up study.	2006-02	16307201
N-acetylaspartylglutamate (NAAG) in Pelizaeus-Merzbacher disease.	2006	16802726
N-acetylaspartylglutamate (NAAG) in spinal cord injury and disease.	2006	16802725
Synthesis of N-acetylaspartyl-glutamate (NAAG) and N-acetylaspartate (NAA) in axons and glia of the crayfish medial giant nerve fiber.	2006	16802722
Functions of N-acetylaspartate and N-acetylaspartylglutamate in brain: evidence of a role in maintenance of higher brain integrative activities of information processing and cognition.	2006	16802707
Expression of N-acetylaspartate and N-acetylaspartylglutamate in the nervous system.	2006	16802702
A brief overview of N-acetylaspartate and N-acetylaspartylglutamate.	2006	16802701
NAAG peptidase inhibitors and their potential for diagnosis and therapy.	2005-12	16341066
Optimized diffusion-weighted spectroscopy for measuring brain glutamate apparent diffusion coefficient on a whole-body MR system.	2005-12	16177956
Neuroprotective effect of N-acetyl-aspartyl-glutamate in combination with mild hypothermia in the endothelin-1 rat model of focal cerebral ischaemia.	2005-12	16135071
Simultaneous high performance liquid chromatographic separation of purines, pyrimidines, N-acetylated amino acids, and dicarboxylic acids for the chemical diagnosis of inborn errors of metabolism.	2005-11	16139832
Neonatal administration of N-acetyl-L-aspartyl-L-glutamate induces early neurodegeneration in hippocampus and alters behaviour in young adult rats.	2005-10-15	16540202
Mice lacking glutamate carboxypeptidase II are protected from peripheral neuropathy and ischemic brain injury.	2005-10	16190866
Quantitative proton MRS of Pelizaeus-Merzbacher disease: evidence of dys- and hypomyelination.	2005-09-13	16157902
Central N-acetyl aspartylglutamate deficit: a possible pathogenesis of schizophrenia.	2005-09	16127367
The neurotransmitter N-acetylaspartylglutamate in models of pain, ALS, diabetic neuropathy, CNS injury and schizophrenia.	2005-09	16055199
The metabotropic glutamate receptor mGluR3 is critically required for hippocampal long-term depression and modulates long-term potentiation in the dentate gyrus of freely moving rats.	2005-09	15635057
Glycyl-L-glutamine disposition in rat choroid plexus epithelial cells in primary culture: role of PEPT2.	2005-08	16078137
Strategies to increase central N-acetyl aspartylglutamate: a potential treatment for schizophrenia and bipolar disorders.	2005-07-15	15949670
Effect of N-acetylaspartylglutamate (NAAG) on non-quantal and spontaneous quantal release of acetylcholine at the neuromuscular synapse of rat.	2005-07	15953368
Metabolic characterization of distinct neuroanatomical regions in rats by magic angle spinning 1H nuclear magnetic resonance spectroscopy.	2005-05	15844164
Regulation of glutamate carboxypeptidase II hydrolysis of N-acetylaspartylglutamate (NAAG) in crayfish nervous tissue is mediated by glial glutamate and acetylcholine receptors.	2005-05	15836619
Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor alpha-induced neurotoxicity in concert with microglial-derived Fas ligand.	2005-03-16	15772355
Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain.	2005-03-01	15653257
In vitro 1H NMR spectroscopy shows an increase in N-acetylaspartylglutamate and glutamine content in the hippocampus of amygdaloid-kindled rats.	2005-03	15748151
High-field localized 1H NMR spectroscopy in the anesthetized and in the awake monkey.	2004-12	15707786
Serotonin1B receptors: from protein to physiological function and behavior.	2004-10	15527863
Quantitative 1H-MRS of healthy human cortex, hippocampus, and thalamus: metabolite concentrations, quantification precision, and reproducibility.	2004-09	15332241
Aspartoacylase deficiency does not affect N-acetylaspartylglutamate level or glutamate carboxypeptidase II activity in the knockout mouse brain.	2004-08-06	15246864
Biosynthesis of NAAG by an enzyme-mediated process in rat central nervous system neurons and glia.	2004-08	15287905
Antinociceptive effects of N-acetylaspartylglutamate (NAAG) peptidase inhibitors ZJ-11, ZJ-17 and ZJ-43 in the rat formalin test and in the rat neuropathic pain model.	2004-07	15233757
Identification of the N-glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity.	2004-06	15152093
Severe hypomyelination associated with increased levels of N-acetylaspartylglutamate in CSF.	2004-05-11	15136672
NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR.	2004-05	15140187
The cloning and characterization of a second brain enzyme with NAAG peptidase activity.	2004-05	15086519
Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3.	2004-04	15030392

Patents

Sample Use Guides

In Vivo Use Guide

Conjunctivitis and blepharoconjunctivitis: 2-6 drops per day

Route of Administration: Topical

In Vitro Use Guide

At low concentrations (20 uM), NAAG reduced rat isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:16:38 GMT 2025` Edited by `admin` on `Mon Mar 31 18:16:38 GMT 2025`
Record UNII	X81L78B3RB
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SPAGLUMIC ACID

Official Name

English

NSC-758468

Preferred Name

English

SPAGLUMIC ACID [MART.]

Common Name

English

spaglumic acid [INN]

Common Name

English

Spaglumic acid [WHO-DD]

Common Name

English

L-GLUTAMIC ACID, N-(N-ACETYL-L-.BETA.-ASPARTYL)-

Common Name

English

Classification Tree Code System Code

WHO-VATC

QR01AC05