Trial reportThe international journal of neuropsychopharmacology2020
A Randomized Trial of the N-Methyl-d-Aspartate Receptor Glycine Site Antagonist Prodrug 4-Chlorokynurenine in Treatment-Resistant Depression.
Trial report in The international journal of neuropsychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02484456 (An Investigation of the Antidepressant Effects of the Glycine Receptor Antagonist AV 101), which is not on this map. Cited by 38 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Investigation of the Antidepressant Effects of the Glycine Receptor Antagonist AV 101 (4-chlorokynurenine) in Major Depressive Disorder
Who cites it
38 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Investigational Drugs for the Treatment of Depression (Part 2): Glutamatergic, Cholinergic, Sestrin Modulators, and Other Agents.Frontiers in pharmacology · 2022Pooled it
- The kynurenine pathway in bipolar disorder: a meta-analysis on the peripheral blood levels of tryptophan and related metabolites.Molecular psychiatry · 2021Pooled it
- Longitudinal study of impact of medication for opioid use disorder on Hamilton Depression Rating Scale.Journal of affective disorders · 2022Trial
- Discovery of the 5-Chlorokynurenine Pathway in Lodopyridone Biosynthesis.Journal of natural products · 2026Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Exploring New Frontiers in Pharmacological Treatment of Depression: A Review on Recent Advances.Current medicinal chemistry · 2026Review
- Anhedonia in Depressive Disorder and Schizophrenia: An Overview of Causes, Diagnosis, and Treatment.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- The therapeutic potential of psilocybin beyond psychedelia through shared mechanisms with ketamine.Molecular psychiatry · 2025Review
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.European archives of psychiatry and clinical neuroscience · 2025Review
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- ThePhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Targeting metaplasticity mechanisms to promote sustained antidepressant actions.Molecular psychiatry · 2024Review
- Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101).Molecular pharmaceutics · 2024Article
- Sex- and suicide-specific alterations in the kynurenine pathway in the anterior cingulate cortex in major depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression.Pharmaceuticals (Basel, Switzerland) · 2023Review
- NMDA Receptor Activation-Dependent Antidepressant-Relevant Behavioral and Synaptic Actions of Ketamine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundKetamine has rapid-acting antidepressant effects but is associated with psychotomimetic and other adverse effects. A 7-chlorokynurenic acid is a potent and specific glycine site N-methyl-d-aspartate receptor antagonist but crosses the blood-brain barrier inefficiently. Its prodrug, L-4-chlorokynurenine (4-Cl-KYN), exerts acute and sustained antidepressant-like effects in rodents and has no reported psychotomimetic effects in either rodents or healthy volunteers. This study examined whether 4-Cl-KYN has rapid antidepressant effects in individuals with treatment-resistant depression.
methodsAfter a 2-week drug-free period, 19 participants with treatment-resistant depression were randomized to receive daily oral doses of 4-Cl-KYN monotherapy (1080 mg/d for 7 days, then 1440 mg/d for 7 days) or placebo for 14 days in a randomized, placebo-controlled, double-blind, crossover manner. The primary outcome measure was the Hamilton Depression Rating Scale score, assessed at several time points over a 2-week period; secondary outcome measures included additional rating scale scores. Pharmacokinetic measures of 7-chlorokynurenic acid and 4-Cl-KYN and pharmacodynamic assessments were obtained longitudinally and included 1H-magnetic resonance spectroscopy brain glutamate levels, resting-state functional magnetic resonance imaging, and plasma and cerebrospinal fluid measures of kynurenine metabolites and neurotrophic factors.
resultsLinear mixed models detected no treatment effects, as assessed by primary and secondary outcome measures. No difference was observed for any of the peripheral or central biological indices or for adverse effects at any time between groups. A 4-Cl-KYN was safe and well-tolerated, with generally minimal associated adverse events.
conclusionsIn this small crossover trial, 4-Cl-KYN monotherapy exerted no antidepressant effects at the doses and treatment duration studied.ClinicalTrials.gov identifier: NCT02484456.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.