7-Chlorokynurenic acid

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7-Chlorokynurenic acid
IUPAC name
7-chloro-4-oxo-1H-quinoline-2-carboxylic acid
Other names
7-chlorokynurenate; 7-CTKA
3D model (JSmol)
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 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 (Ki = 0.59 mM).[5]

See also[edit]


  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. PMC 282010Freely accessible. PMID 2842779. doi:10.1073/pnas.85.17.6547. 
  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. PMC 3756114Freely accessible. PMID 23611177. doi:10.1503/jpn.120228. 
  3. ^ a b 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. PMID 9051744. doi:10.1097/00001756-199612200-00004. 
  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. ISSN 1474-1776. PMID 23237916. doi:10.1038/nrd3793. 
  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. PMID 9776380. doi:10.1016/s0028-3908(98)00080-x.