ArticlePsychopharmacology2023
Antidepressant effects of novel positive allosteric modulators of Trk-receptor mediated signaling - a potential therapeutic concept?
Article in Psychopharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- The role of zinc homeostasis in major depressive disorder: heterogeneous pathological mechanisms and therapeutic implications.Annals of medicine · 2026Review
- Signs of antidepressant-like effects of temozolomide as measured in the forced-swim test in adult rats.Pharmacological reports : PR · 2026Article
- Low Dose Ketamine Preconditions Astrocyte Mitochondria to Achieve Antidepressant Efficacy via Adenosine, Humanin, and Melatonin Upregulation and Efflux.Alpha psychiatry · 2026Article
- Synaptic Plasticity-Intrinsic Excitability and Antidepressant Discovery.Biomedicines · 2026Review
- Small-Molecule Trk Agonists: Where Do We Go from Here?Journal of medicinal chemistry · 2025Review
- DSP-6745, a novel 5-hydroxytryptamine modulator with rapid antidepressant, anxiolytic, antipsychotic and procognitive effects.Psychopharmacology · 2024Article
- Positive Allosteric Modulators of Trk Receptors for the Treatment of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- The multifaceted effects of fluoxetine treatment on cognitive functions.Frontiers in pharmacology · 2024Review
- Neuroprotective and Disease-Modifying Effects of the Triazinetrione ACD856, a Positive Allosteric Modulator of Trk-Receptors for the Treatment of Cognitive Dysfunction in Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Electroconvulsive seizures regulate various stages of hippocampal cell genesis and mBDNF at different times after treatment in adolescent and adult rats of both sexes.Frontiers in molecular neuroscience · 2023Article
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
No grant is acknowledged in the PubMed record.
Abstract
backgroundMajor depressive disorder (MDD) is defined as a complex mental disorder which is characterized by a pervasive low mood and aversion to activity. Several types of neurotransmitter systems e.g. serotonergic, glutamatergic and noradrenergic systems have been suggested to play an important role in the origination of depression, but neurotrophins such as brain derived neurotrophic factor (BDNF) have also been implicated in the disease process.
objectivesThe purpose of this study was to examine the effects of a newly developed class of molecules, characterized as positive allosteric modulators of neurotrophin/Trk receptor mediated signaling (Trk-PAM), on neurotransmitter release and depression-like behavior in vivo.
methodsThe effect of and possible interaction of neurotrophin/Trk signaling pathways with serotonergic and glutamatergic systems in the modulation of depression-related responses was studied using newly developed Trk-PAM compounds (ACD855, ACD856 and AC26845), as well as ketamine and fluoxetine in the forced swim test (FST) in rodents. Moreover, in vivo microdialysis in freely moving rats was used to assess changes in neurotransmitter levels in the rat.
resultsThe results from the study show that several different compounds, which all potentiate Trk-receptor mediated signaling, display antidepressant-like activity in the FST. Moreover, the data also indicate that the effects of both fluoxetine and ketamine in the FST, both used in clinical practice, are mediated via BDNF/TrkB signaling, which could have implications for novel therapies in MDD.
conclusionsTrk-PAMs could provide an interesting avenue for the development of novel therapeutics in this area.
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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.