Chemistry:7-Chlorokynurenic acid
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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
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| Identifiers | |
3D model (JSmol)
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PubChem CID
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| Properties | |
| C10H6Cl1N1O3 | |
| Molar mass | 223.61254 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 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.[1] It produces ketamine-like rapid antidepressant effects in animal models of depression.[2][3] However, 7-CKA is unable to cross the blood-brain-barrier, and for this reason, is unsuitable for clinical use.[4] 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,[4][5][6] and anti-nociception.[7] 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).[8]
See also
References
- ↑ "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. 1988. doi:10.1073/pnas.85.17.6547. PMID 2842779. Bibcode: 1988PNAS...85.6547K.
- ↑ 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" (in en). Sci. Signal. 9 (458): ra123. doi:10.1126/scisignal.aai7884. ISSN 1945-0877. PMID 27965425.
- ↑ Zanos, Panos; Piantadosi, Sean C.; Wu, Hui-Qiu; Pribut, Heather J.; Dell, Matthew J.; Can, Adem; Snodgrass, H. Ralph; Zarate, Carlos A. et al. (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. PMID 26265321.
- ↑ 4.0 4.1 "Facilitated brain uptake of 4-chlorokynurenine and conversion to 7-chlorokynurenic acid". NeuroReport 8 (1): 15–8. 1996. doi:10.1097/00001756-199612200-00004. PMID 9051744. https://zenodo.org/record/1234762.
- ↑ 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. 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.
- ↑ 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" (in en). Scandinavian Journal of Pain 17 (1): 243–251. doi:10.1016/j.sjpain.2017.05.004. ISSN 1877-8860. PMID 29229209. http://www.scandinavianjournalpain.com/article/S1877-8860(17)30128-3/abstract.
- ↑ "Substituted quinolines as inhibitors of L-glutamate transport into synaptic vesicles". Neuropharmacology 37 (7): 839–46. 1998. doi:10.1016/s0028-3908(98)00080-x. PMID 9776380.
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