ArticleBioscience reports2022
Inflammation and serotonin deficiency in major depressive disorder: molecular docking of antidepressant and anti-inflammatory drugs to tryptophan and indoleamine 2,3-dioxygenases.
Article in Bioscience reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Plasma Instead of Serum Avoids Critical Confounding of Clinical Metabolomics Studies by Platelets.Journal of proteome research · 2024Trial
- The interaction between kynurenine pathway, suicidal ideation and augmentation therapy with minocycline in patients with treatment-resistant depression.Journal of psychopharmacology (Oxford, England) · 2023Trial
- The Tryptophan-Kynurenine Pathway as a Key Mediator of the Gut-Brain Axis in Depression and Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Docking Analysis of Drugs Used in the Treatment of Alzheimer's Disease, Using Cell Membrane Receptors and Enzymes of the Kynurenine Pathway: A Pilot Study.International journal of molecular sciences · 2026Article
- Design, Synthesis, and Biological Evaluation of Novel Morpholine-Coumarin Derivatives for Inflammation-Associated Depression.Biomolecules · 2026Article
- Harnessing Dietary Tryptophan: Bridging the Gap Between Neurobiology and Psychiatry in Depression Management.International journal of molecular sciences · 2026Review
- The Complex World of Kynurenic Acid: Reflections on Biological Issues and Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Low indoleamine 2, 3 dioxygenase (IDO) activity is associated with psycho-obstetric risk.Pregnancy hypertension · 2024Article
- The major biogenic amine metabolites in mood disorders.Frontiers in psychiatry · 2024Review
- Imipramine Administration inPharmaceuticals (Basel, Switzerland) · 2023Article
- Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies.International journal of molecular sciences · 2023Review
- Kynurenine pathway of tryptophan metabolism in pathophysiology and therapy of major depressive disorder.World journal of psychiatry · 2023Review
- Life-Threatening Cardiogenic Shock Related to Venlafaxine Poisoning-A Case Report with Metabolomic Approach.Metabolites · 2023Article
- Optimizing Treatment for Major Depressive Disorder in Adolescents: The Impact of Intradermal Acupuncture - A Randomized Controlled Trial Protocol.Neuropsychiatric disease and treatment · 2023Article
- Tryptophan Metabolism in Depression: A Narrative Review with a Focus on Serotonin and Kynurenine Pathways.International journal of molecular sciences · 2022Review
- Involvement of inflammatory responses in the brain to the onset of major depressive disorder due to stress exposure.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The roles of the kynurenine pathway (KP) of tryptophan (Trp) degradation in serotonin deficiency in major depressive disorder (MDD) and the associated inflammatory state are considered in the present study. Using molecular docking in silico, we demonstrate binding of antidepressants to the crystal structure of tryptophan 2,3-dioxygenase (TDO) but not to indoleamine 2,3-dioxygenase (IDO). TDO is inhibited by a wide range of antidepressant drugs. The rapidly acting antidepressant ketamine does not dock to either enzyme but may act by inhibiting kynurenine monooxygenase thereby antagonising glutamatergic activation to normalise serotonin function. Antidepressants with anti-inflammatory properties are unlikely to act by direct inhibition of IDO but may inhibit IDO induction by lowering levels of proinflammatory cytokines in immune-activated patients. Of six anti-inflammatory drugs tested, only salicylate docks strongly to TDO and apart from celecoxib, the other five dock to IDO. TDO inhibition remains the major common property of antidepressants and TDO induction the most likely mechanism of defective serotonin synthesis in MDD. TDO inhibition and increased free Trp availability by salicylate may underpin the antidepressant effect of aspirin and distinguish it from other nonsteroidal anti-inflammatory drugs. The controversial findings with IDO in MDD patients with an inflammatory state can be explained by IDO induction being overridden by changes in subsequent KP enzymes influencing glutamatergic function. The pathophysiology of MDD may be underpinned by the interaction of serotonergic and glutamatergic activities.
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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.