ArticleMolecular psychiatry2020
Antidepressant efficacy of a selective organic cation transporter blocker in a mouse model of depression.
Article in Molecular psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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.
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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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Proprietary Medicines ContainingFrontiers in pharmacology · 2022Pooled it
- It's not all DAT: harnessing the potential of organic cation transporter 3 inhibition to selectively attenuate amphetamine reinforcement and dopamine release.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The DRN-VLO pathway via distinct 5-HT synaptic mechanisms modulates neuropathic pain-induced depressive-like behaviors in mice.The journal of headache and pain · 2025Article
- Serotonergic Regulation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Chronic corticosterone exposure causes anxiety- and depression-related behaviors with altered gut microbial and brain metabolomic profiles in adult male C57BL/6J mice.Molecular brain · 2024Article
- Organic cation transporters in psychiatric and substance use disorders.Pharmacology & therapeutics · 2024Review
- Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.Translational psychiatry · 2023Article
- Structural basis of organic cation transporter-3 inhibition.Nature communications · 2022Article
- Mycotherapy: Potential of Fungal Bioactives for the Treatment of Mental Health Disorders and Morbidities of Chronic Pain.Journal of fungi (Basel, Switzerland) · 2022Review
- MPPInternational journal of molecular sciences · 2022Article
- Learned Immobility Produces Enduring Impairment of the HPA Axis Reactivity in Mice without Replicating the Broad Spectrum of Depressive-Like Phenotype.International journal of molecular sciences · 2021Article
- Organic Cation Transporters in Psychiatric Disorders.Handbook of experimental pharmacology · 2021Article
- General Overview of Organic Cation Transporters in Brain.Handbook of experimental pharmacology · 2021Article
- Antidepressant-relevant behavioral and synaptic molecular effects of long-term fasudil treatment in chronically stressed male rats.Neurobiology of stress · 2020Article
- Effect of concurrent organic cation transporter blockade on norepinephrine clearance inhibiting- and antidepressant-like actions of desipramine and venlafaxine.European journal of pharmacology · 2020Article
- Article
- Advances in depression research: second special issue, 2020, with highlights on biological mechanisms, clinical features, co-morbidity, genetics, imaging, and treatment.Molecular psychiatry · 2020Article
- Advances in depression research: special issue, 2020, with three research articles by Paul Greengard.Molecular psychiatry · 2020Article
- Metabonomic Profile and Signaling Pathway Prediction of Depression-Associated Suicidal Behavior.Frontiers in psychiatry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Current antidepressants act principally by blocking monoamine reuptake by high-affinity transporters in the brain. However, these antidepressants show important shortcomings such as slow action onset and limited efficacy in nearly a third of patients with major depression disorder. Here, we report the development of a prodrug targeting organic cation transporters (OCT), atypical monoamine transporters recently implicated in the regulation of mood. Using molecular modeling, we designed a selective OCT2 blocker, which was modified to increase brain penetration. This compound, H2-cyanome, was tested in a rodent model of chronic depression induced by 7-week corticosterone exposure. In male mice, prolonged administration of H2-cyanome induced positive effects on several behaviors mimicking symptoms of depression, including anhedonia, anxiety, social withdrawal, and memory impairment. Importantly, in this validated model, H2-cyanome compared favorably with the classical antidepressant fluoxetine, with a faster action on anhedonia and better anxiolytic effects. Integrated Z-scoring across these depression-like variables revealed a lower depression score for mice treated with H2-cyanome than for mice treated with fluoxetine for 3 weeks. Repeated H2-cyanome administration increased ventral tegmental area dopaminergic neuron firing, which may underlie its rapid action on anhedonia. H2-cyanome, like fluoxetine, also modulated several intracellular signaling pathways previously involved in antidepressant response. Our findings provide proof-of-concept of antidepressant efficacy of an OCT blocker, and a mechanistic framework for the development of new classes of antidepressants and therapeutic alternatives for resistant depression and other psychiatric disturbances such as anxiety.
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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.