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| Names | |
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| Preferred IUPAC name 7-Chloro-4-oxo-1,4-dihydroquinoline-2-carboxylic acid | |
| Other names 7-Chlorokynurenate; 7-CTKA | |
| Identifiers | |
| CAS Number | |
| 3D model (JSmol) | |
| ChemSpider | |
| ECHA InfoCard | 100.038.088 
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| PubChem CID | |
| UNII | |
| CompTox Dashboard (EPA) | |
SMILES
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| Properties | |
| Chemical formula | C10H6ClNO3 |
| Molar mass | 223.61 g·mol |
| Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references | |
7-Chlorokynurenic acid (7-CKA) is a tool compound that acts as a potent and selective competitive antagonist of the glycine site of the NMDA receptor. It produces ketamine-like rapid antidepressant effects in animal models of depression. However, 7-CKA is unable to cross the blood-brain-barrier, and for this reason, is unsuitable for clinical use. 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, and anti-nociception. 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 (Ki = 0.59 mM).
See also
References
- 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. Bibcode:1988PNAS...85.6547K. doi:10.1073/pnas.85.17.6547. PMC 282010. PMID 2842779.
- Zhang, Ke; Xu, Ting; Yuan, Zhongmin; Wei, Zhisheng; Yamaki, Vitor Nagai; Huang, Mingfa; Huganir, Richard L.; Cai, Xiang (2016-12-13). "Essential roles of AMPA receptor GluA1 phosphorylation and presynaptic HCN channels in fast-acting antidepressant responses of ketamine". Sci. Signal. 9 (458): ra123. doi:10.1126/scisignal.aai7884. ISSN 1945-0877. PMC 5564288. PMID 27965425.
- Zanos, Panos; Piantadosi, Sean C.; Wu, Hui-Qiu; Pribut, Heather J.; Dell, Matthew J.; Can, Adem; Snodgrass, H. Ralph; Zarate, Carlos A.; Schwarcz, Robert (October 2015). "The Prodrug 4-Chlorokynurenine Causes Ketamine-Like Antidepressant Effects, but Not Side Effects, by NMDA/GlycineB-Site Inhibition". The Journal of Pharmacology and Experimental Therapeutics. 355 (1): 76–85. doi:10.1124/jpet.115.225664. ISSN 1521-0103. PMC 4576668. PMID 26265321.
- ^ 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. S2CID 32729671.
- Gerhard, Danielle M.; Wohleb, Eric S.; Duman, Ronald S. (March 2016). "Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity". Drug Discovery Today. 21 (3): 454–464. doi:10.1016/j.drudis.2016.01.016. ISSN 1878-5832. PMC 4803609. PMID 26854424.
- 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. S2CID 31914015.
- Wallace, Mark; White, Alexander; Grako, Kathy A.; Lane, Randal; Cato, Allen (Jo); Snodgrass, H. Ralph (2017-06-14). "Randomized, double-blind, placebo-controlled, dose-escalation study: Investigation of the safety, pharmacokinetics, and antihyperalgesic activity of l-4-chlorokynurenine in healthy volunteers". Scandinavian Journal of Pain. 17 (1): 243–251. doi:10.1016/j.sjpain.2017.05.004. ISSN 1877-8860. PMID 29229209. S2CID 46873455.
- 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. S2CID 39853026.