ArticlePharmacology research & perspectives2021
Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers.
Article in Pharmacology research & perspectives, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Microglial GPR35 Ameliorates Epileptogenesis and Neuroinflammation via PDGFA Domain 2 Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tryptophan metabolites 3-hydroxykynurenine (3HK) and 3-hydroxyanthranilic acid (3HAA) increase oxidative stress and impair osteoblastic bone formation.The Journal of biological chemistry · 2026Article
- The tryptophan-kynurenine pathway in cardiovascular diseases: mechanistic insights and therapeutic opportunities.Frontiers in cardiovascular medicine · 2026Review
- Potential Region-Specific Neuroprotective Effects of Kynurenine Administration in Healthy Rodents Using High-Resolution Mass Spectrometry.ACS chemical neuroscience · 2025Article
- Kynurenine acts as a signaling molecule to attenuate pulmonary fibrosis by enhancing the AHR-PTEN axis.Journal of advanced research · 2025Article
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Potential Role of Glutamate Receptors and their Antagonists or Modulators in Migraine Therapy.Current neuropharmacology · 2025Review
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges.International journal of molecular sciences · 2024Review
- Dietary Kynurenine Pathway Metabolites-Source, Fate, and Chromatographic Determinations.International journal of molecular sciences · 2023Review
- Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain.International journal of molecular sciences · 2023Review
- Kynurenine/Aryl Hydrocarbon Receptor Modulates Mitochondria-Mediated Oxidative Stress and Neuronal Apoptosis in Experimental Intracerebral Hemorrhage.Antioxidants & redox signaling · 2022Article
- Review
- Peripheral N-methyl-D-aspartate receptor activation contributes to monosodium glutamate-induced headache but not nausea behaviours in rats.Scientific reports · 2022Article
- On the Antioxidant Properties of L-Kynurenine: An Efficient ROS Scavenger and Enhancer of Rat Brain Antioxidant Defense.Antioxidants (Basel, Switzerland) · 2021Article
- Neurodegeneration in Multiple Sclerosis: Symptoms of Silent Progression, Biomarkers and Neuroprotective Therapy-Kynurenines Are Important Players.Molecules (Basel, Switzerland) · 2021Review
- Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).Frontiers in medicine · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The kynurenine pathway (KP) is the main path for tryptophan metabolism, and it represents a multitude of potential sites for drug discovery in neuroscience, including pain, stroke, and epilepsy. L-kynurenine (LKYN), the first active metabolite in the pathway, emerges to be a prodrug targeting glutamate receptors. The safety, tolerability, pharmacokinetics, and pharmacodynamics of LKYN in humans have not been previously investigated. In an open-label, single ascending dose study, six participants received an intravenous infusion of 50, 100, and 150 µg/kg LKYN and new six participants received an intravenous infusion of 0.3, 0.5, 1, and 5 mg/kg LKYN. To compare the pharmacological effects between species, we investigated in vivo the vascular effects of LKYN in rats. In humans, LKYN was safe and well-tolerated at all dose levels examined. After infusion, LKYN plasma concentration increased significantly over time 3.23 ± 1.12 µg/mL (after 50 µg/kg), 4.04 ± 1.1 µg/mL (after 100 µg/kg), and 5.25 ± 1.01 µg/mL (after 150 µg/kg) (p ≤ 0.001). We observed no vascular changes after infusion compared with baseline. In rats, LKYN had no effect on HR and MAP and caused no dilation of dural and pial arteries. This first-in-human study of LKYN showed that LKYN was safe and well-tolerated after intravenous infusion up to 5 mg/kg over 20 minutes. The lack of change in LKYN metabolites in plasma suggests a relatively slow metabolism of LKYN and no or little feed-back effect of LKYN on its synthesis. The therapeutic potential of LKYN in stroke and epilepsy should be explored in future studies in humans.
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Registered trials
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