|Synonyms||4-Cl-KYN; AV-101; 3-(4-Chloroanthraniloyl)-DL-alanine|
|Bioavailability||39–84% (rodents); ≥ 31% (humans)|
|Elimination half-life||2–3 hours|
|Chemical and physical data|
|Molar mass||242.659 g/mol g·mol−1|
|3D model (JSmol)|
L-4-Chlorokynurenine (4-Cl-KYN; developmental code name AV-101) is an orally active small molecule prodrug of 7-chlorokynurenic acid, a NMDA receptor antagonist. It appears to be a rapid-acting antidepressant.
AV-101 was discovered at Marion Merrell Dow and its biological activity was explored at University of Maryland. It underwent initial development at Artemis Neuroscience which was acquired by VistaGen in 2003. As of 2016 it was in a Phase II clinical trial for major depressive disorder.
4-Chlorokynurenine penetrates the blood–brain barrier via the large neutral amino acid transporter 1. In the central nervous system it is converted to 7-chlorokynurenic acid by kynurenine aminotransferase in astrocytes.
Artemis Neuroscience was formed to develop work done by University of Maryland professor Robert Schwartz in collaboration with scientists at Marion Merrell Dow (which became part of Sanofi by way of Aventis); this work included AV-101.
VistaGen acquired AV-101 when it acquired Artemis in 2003.
AV-101 showed efficacy in animal model of Huntington's disease and showed rapid-acting antidepressant effects similar to ketamine in the forced-swim test and two other behavioral models of depression in rodents.
By 2013 AV-101 had successfully gone through two Phase I clinical trials.
It has been found to be effective for neuropathic pain in animal studies. 
- Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (1997). "Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit". Neuron. 18 (3): 493–503. doi:10.1016/S0896-6273(00)81249-0. PMID 9115742.
- Smith, Quentin R.; Lockman, Paul R. (2011). "11. Prodrug Approaches for Central Nervous System Delivery". In Mannhold, R; Kubinyi, H; Folkers, G (eds.). Prodrugs and Targeted Delivery: Towards Better ADME Properties Volume 47 of Methods and Principles in Medicinal Chemistry. John Wiley & Sons. p. 259. ISBN 9783527633180.
- Vécsei, L; Szalárdy, L; Fülöp, F; Toldi, J (January 2013). "Kynurenines in the CNS: recent advances and new questions". Nature Reviews. Drug Discovery. 12 (1): 64–82. doi:10.1038/nrd3793. PMID 23237916.
- "School of Medicine Professor Wins University System of Maryland (USM) Board of Regents Award". University of Maryland. April 6, 2007.
- "Press Release: VistaGen Therapeutics Acquires Artemis Neuroscience, Inc. - Enters Late-Stage Preclinical Development Program for Lead Epilepsy Drug Candidate -". PR Newswire. November 19, 2003.
- "VistaGen Therapeutics, Inc. 8-K Exhibit 10-26". SEC Edgar. May 16, 2011. See 8-K Index page at SEC Edgar.
- "VistaGen acquires Artemis Neuroscience". San Francisco Business Times. November 19, 2003.
- Flight, Monica Hoyos (29 November 2013). "Trial watch: Phase II boost for glutamate-targeted antidepressants". Nature Reviews Drug Discovery. 12 (12): 897. doi:10.1038/nrd4178. PMID 24287771.
- Gerhard, DM; Wohleb, ES; Duman, RS (March 2016). "Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity". Drug Discovery Today. 21 (3): 454–64. doi:10.1016/j.drudis.2016.01.016. PMC 4803609. PMID 26854424.
- Yaksh, Tony L.; Schwarcz, Robert; Snodgrass, H. Ralph (October 2017). "Characterization of the Effects of L-4-Chlorokynurenine on Nociception in Rodents". The Journal of Pain. 18 (10): 1184–1196. doi:10.1016/j.jpain.2017.03.014. ISSN 1526-5900.