7-Chlorokynurenic acid

7-Chlorokynurenic acid

Systematic (IUPAC) name
7-chloro-4-oxo-1H-quinoline-2-carboxylic acid
Identifiers
CAS Number	18000-24-3
ATC code	None
PubChem	CID 1884
ChemSpider	1813
Synonyms	7-chlorokynurenate; 7-CTKA
Chemical data
Formula	C10H6ClNO3
Molar mass	223.61254 g/mol
SMILES C1=CC2=C(C=C1Cl)NC(=CC2=O)C(=O)O
InChI InChI=1S/C10H6ClNO3/c11-5-1-2-6-7(3-5)12-8(10(14)15)4-9(6)13/h1-4H,(H,12,13)(H,14,15) Key:UAWVRVFHMOSAPU-UHFFFAOYSA-N

7-Chlorokynurenic acid (7-CKA) is a drug that acts as a potent and selective noncompetitive antagonist of the glycine site of the NMDA receptor.^[1] It produces ketamine-like rapid antidepressant effects in animal models of depression.^[2] However, 7-CKA is unable to cross the blood-brain-barrier, and for this reason, is unsuitable for clinical use.^[3] As a result, a centrally-penetrant prodrug of 7-CKA, 4-chlorokynurenine (AV-101), has been developed for use in humans, and is being studied in clinical trials as a potential treatment for major depressive disorder.^[3][4] In addition to antagonizing the NMDA receptor, 7-CKA also acts as a potent inhibitor of the reuptake of glutamate into synaptic vesicles (or as a vesicular glutamate reuptake inhibitor), an action that it mediates via competitive blockade of vesicular glutamate transporters (K_i = 0.59 mM).^[5]

See also

• 5,7-Dichlorokynurenic acid
• Evans blue
• Kynurenic acid
• Xanthurenic acid

References

1. Kemp JA, Foster AC, Leeson PD, Priestley T, Tridgett R, Iversen LL, Woodruff GN (1988). "7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex". Proc. Natl. Acad. Sci. U.S.A. 85 (17): 6547–50. doi:10.1073/pnas.85.17.6547. PMC: 282010. PMID 2842779.
2. Zhu WL, Wang SJ, Liu MM, Shi HS, Zhang RX, Liu JF, Ding ZB, Lu L (2013). "Glycine site N-methyl-D-aspartate receptor antagonist 7-CTKA produces rapid antidepressant-like effects in male rats". J Psychiatry Neurosci 38 (5): 306–16. doi:10.1503/jpn.120228. PMC: 3756114. PMID 23611177.
3. Hokari M, Wu HQ, Schwarcz R, Smith QR (1996). "Facilitated brain uptake of 4-chlorokynurenine and conversion to 7-chlorokynurenic acid". NeuroReport 8 (1): 15–8. doi:10.1097/00001756-199612200-00004. PMID 9051744.
4. Vécsei, László; Szalárdy, Levente; Fülöp, Ferenc; Toldi, József (2012). "Kynurenines in the CNS: recent advances and new questions". Nature Reviews Drug Discovery 12 (1): 64–82. doi:10.1038/nrd3793. ISSN 1474-1776. PMID 23237916.
5. Bartlett RD, Esslinger CS, Thompson CM, Bridges RJ (1998). "Substituted quinolines as inhibitors of L-glutamate transport into synaptic vesicles". Neuropharmacology 37 (7): 839–46. doi:10.1016/s0028-3908(98)00080-x. PMID 9776380.