Quinolinic acid

Quinolinic acid
IUPAC name Pyridine-2,3-dicarboxylic acid
Identifiers
CAS number	89-00-9 Y
PubChem	1066
ChEMBL	CHEMBL286204 N
Jmol-3D images	Image 1
SMILES O=C(O)c1ncccc1C(O)=O
InChI InChI=1/C7H5NO4/c9-6(10)4-2-1-3-8-5(4)7(11)12/h1-3H,(H,9,10)(H,11,12)
Properties
Molecular formula	C7H5NO4
Molar mass	167.12 g/mol
Melting point	185–190 °C (dec.)
Hazards
MSDS	External MSDS
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Quinolinic acid is a dicarboxylic acid. It may be prepared by the oxidation of quinoline, either electrochemically,^[1] or with acidic hydrogen peroxide.^[2]

Quinolinic acid is a downstream kynurenine pathway metabolite of tryptophan. It acts as an NMDA agonist.^[3] Quinolinic acid has a potent neurotoxic effect and involved in neurodegenerative processes in the brain, such as in AIDS dementia complex, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis and Parkinson's disease.^[4] Within the brain, quinolinic acid is only produced by activated microglia and macrophages.^[5]

Norharmane, suppresses the production of quinolinic acid, 3OH-kynurenine and nitric oxide synthase, thereby acting as a neuroprotectant.^[6] Natural phenols such as catechin hydrate, curcumin and epigallocatechin gallate reduce the neurotoxicity of quinolinic acid, via anti-oxidant and possibly calcium influx mechanisms.^[7] COX-2 inhibitors have also demonstrated protective properties against the neurotoxic properties of quinolinic acid,^[8] and these COX-2 inhibitors have demonstrated some evidence of efficacy in mental health disorders such as major depressive disorder as well as schizophrenia.^[9]

Quinolinic acid decomposes at 185–190 °C by decarboxylation to nicotinic acid.

References

1. ^ EP 0159769, Toomey Jr., Joseph E., "Electrochemical oxidation of pyridine bases", assigned to Reilly Industries, Inc. 
2. ^ US Patent 4420616, Ikegami, Seishi & Hatano, Yoshihiro, "Oxidative process for the preparation of copper quinolinate", assigned to Yamamoto Kagaku Gosei KK 
3. ^ Misztal M, Frankiewicz T, Parsons CG, Danysz W (January 1996). "Learning deficits induced by chronic intraventricular infusion of quinolinic acid--protection by MK-801 and memantine". Eur. J. Pharmacol. 296 (1): 1–8. doi:10.1016/0014-2999(95)00682-6. PMID 8720470. 
4. ^ Guillemin, G. (2005). "Quinolinic acid selectively induces apoptosis of human astocytes: Potential role in AIDS dementia complex". J Neuroinflammation 2 (16). 
5. ^ Guillemin, G. (2003). "Expression of the kynurenine pathway enzymes in human microglia and macrophages". Adv Exp Med Biol 527. 
6. ^ Chiarugi A, Dello Sbarba P, Paccagnini A, Donnini S, Filippi S, Moroni F (August 2000). "Combined inhibition of indoleamine 2,3-dioxygenase and nitric oxide synthase modulates neurotoxin release by interferon-gamma-activated macrophages". J. Leukoc. Biol. 68 (2): 260–6. PMID 10947071. http://www.jleukbio.org/content/68/2/260.long. 
7. ^ Braidy N, Grant R, Adams S, Guillemin GJ (January 2010). "Neuroprotective effects of naturally occurring polyphenols on quinolinic acid-induced excitotoxicity in human neurons". FEBS J. 277 (2): 368–82. doi:10.1111/j.1742-4658.2009.07487.x. PMID 20015232. 
8. ^ Kalonia H, Kumar P, Kumar A, Nehru B (March 2010). "Protective effect of rofecoxib and nimesulide against intra-striatal quinolinic acid-induced behavioral, oxidative stress and mitochondrial dysfunctions in rats". Neurotoxicology 31 (2): 195–203. doi:10.1016/j.neuro.2009.12.008. PMID 20043943. 
9. ^ Müller N (January 2010). "COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence". Curr Opin Investig Drugs 11 (1): 31–42. PMID 20047157.