ArticleChemistry & biology2009
Amitriptyline is a TrkA and TrkB receptor agonist that promotes TrkA/TrkB heterodimerization and has potent neurotrophic activity.
Article in Chemistry & biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Transcranial magnetic stimulation therapy for central post-stroke pain: systematic review and meta-analysis.Frontiers in neuroscience · 2024Pooled it
- A De Novo Peptide That Induces Axonal Growth Through TrkB Activation.Chembiochem : a European journal of chemical biology · 2026Article
- IIC-DTI: A Contrastive Learning Enhanced Inter-Intra Molecular Fusing Framework for Drug-Target Interaction Prediction.Interdisciplinary sciences, computational life sciences · 2026Article
- Molecular neurobiological insights on integrative role of Trk neurotrophic receptors and their small-molecule agonists in neurodegenerative conditions.Experimental brain research · 2026Review
- Integrated computational-based design of putative dual TrkA/TrkB agonists for Alzheimer's disease: pharmacophore modelling, docking, MM/GBSA, DFT and dynamics studies.Frontiers in bioinformatics · 2026Article
- Small-Molecule Trk Agonists: Where Do We Go from Here?Journal of medicinal chemistry · 2025Review
- Amitriptyline for the prevention of post herpetic neuralgia: study protocol for the ATHENA study.Skin health and disease · 2025Article
- Role of Brain Derived Neurotrophic Factor and Related Therapeutic Strategies in Central Post-Stroke Pain.Neurochemical research · 2024Review
- BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy.Journal of cellular and molecular medicine · 2024Review
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- Linking Hypothermia and Altered Metabolism with TrkB Activation.ACS chemical neuroscience · 2023Article
- Neurotrophin mimetics and tropomyosin kinase receptors: a futuristic pharmacological tool for Parkinson's.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Review
- Precision Medicine in Antidepressants Treatment.Handbook of experimental pharmacology · 2023Review
- Effects of the Antidepressant Amitriptyline on Juvenile Brown Trout and Their Modulation by Microplastics.Toxics · 2022Article
- BDNF as a Mediator of Antidepressant Response: Recent Advances and Lifestyle Interactions.International journal of molecular sciences · 2022Review
- Migraine Pharmacological Treatment and Cognitive Impairment: Risks and Benefits.International journal of molecular sciences · 2022Review
- Toward in vivo proof of binding ofEJNMMI research · 2022Article
- Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[International journal of molecular sciences · 2022Article
- Therapeutic strategies for tauopathies and drug repurposing as a potential approach.Biochemical pharmacology · 2022Review
- Development and Biological Characterization of a Novel Selective TrkA Agonist with Neuroprotective Properties against Amyloid Toxicity.Biomedicines · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Neurotrophins, the cognate ligands for the Trk receptors, are homodimers and induce Trk dimerization through a symmetric bivalent mechanism. We report here that amitriptyline, an antidepressant drug, directly binds TrkA and TrkB and triggers their dimerization and activation. Amitriptyline, but not any other tricyclic or selective serotonin reuptake inhibitor antidepressants, promotes TrkA autophosphorylation in primary neurons and induces neurite outgrowth in PC12 cells. Amitriptyline binds the extracellular domain of both TrkA and TrkB and promotes TrkA-TrkB receptor heterodimerization. Truncation of amitriptyline binding motif on TrkA abrogates the receptor dimerization by amitriptyline. Administration of amitriptyline to mice activates both receptors and significantly reduces kainic acid-triggered neuronal cell death. Inhibition of TrkA, but not TrkB, abolishes amitriptyline's neuroprotective effect without impairing its antidepressant activity. Thus, amitriptyline acts as a TrkA and TrkB agonist and possesses marked neurotrophic activity.
Indexed as
Identifiers
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.