Trial reportBritish journal of pharmacology2012
Preclinical and clinical characterization of the selective 5-HT(1A) receptor antagonist DU-125530 for antidepressant treatment.
Trial report in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01119430 (Fluoxetine Versus Fluoxetine Plus DU125530 in Latency of Antidepressant Response Shortening in Major Depressive Disorder), which is not on this map. Cited by 17 papers.
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.
Fluoxetine Versus Fluoxetine Plus DU125530 in Latency of Antidepressant Response Shortening in Major Depressive Disorder
Who cites it
17 citing papers in PubMed, 46 citations in OpenAlex.
- The effects of serotonin modulation on medial prefrontal connectivity strength and stability: A pharmacological fMRI study with citalopram.Progress in neuro-psychopharmacology & biological psychiatry · 2018Trial
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Major depressive disorder: hypothesis, mechanism, prevention and treatment.Signal transduction and targeted therapy · 2024Review
- The Serotonin 1A (5-HTCNS drugs · 2023Review
- A new approach to 'on-demand' treatment of lifelong premature ejaculation by treatment with a combination of a 5-HTFrontiers in neuroscience · 2023Article
- 5-HT Receptors and the Development of New Antidepressants.International journal of molecular sciences · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- How do antidepressants work? New perspectives for refining future treatment approaches.The lancet. Psychiatry · 2017Review
- Computational and biological evidences on the serotonergic involvement of SeTACN antidepressant-like effect in mice.PloS one · 2017Article
- Functional Selectivity and Antidepressant Activity of Serotonin 1A Receptor Ligands.International journal of molecular sciences · 2015Review
- Antidepressant- and Anxiolytic-Like Effects of New Dual 5-HT₁A and 5-HT₇ Antagonists in Animal Models.PloS one · 2015Article
- Targeting melanocyte and melanoma stem cells by 8-hydroxy-2-dipropylaminotetralin.Archives of biochemistry and biophysics · 2014Article
- The role of different serotonin receptor subtypes in seizure susceptibility.Experimental brain research · 2014Review
- The effects of LPM570065, a novel triple reuptake inhibitor, on extracellular serotonin, dopamine and norepinephrine levels in rats.PloS one · 2014Article
- Serotonin 5-HT1A receptors as targets for agents to treat psychiatric disorders: rationale and current status of research.CNS drugs · 2013Review
- Future directions for serotonin and antidepressants.ACS chemical neuroscience · 2013Article
- Acute 5-HT₁A autoreceptor knockdown increases antidepressant responses and serotonin release in stressful conditions.Psychopharmacology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe antidepressant efficacy of selective 5-HT reuptake inhibitors (SSRI) and other 5-HT-enhancing drugs is compromised by a negative feedback mechanism involving 5-HT(1A) autoreceptor activation by the excess 5-HT produced by these drugs in the somatodendritic region of 5-HT neurones. 5-HT(1A) receptor antagonists augment antidepressant-like effects in rodents by preventing this negative feedback, and the mixed β-adrenoceptor/5-HT(1A) receptor antagonist pindolol improves clinical antidepressant effects by preferentially interacting with 5-HT(1A) autoreceptors. However, it is unclear whether 5-HT(1A) receptor antagonists not discriminating between pre- and post-synaptic 5-HT(1A) receptors would be clinically effective. EXPERIMENTAL APPROACH: We characterized the pharmacological properties of the 5-HT(1A) receptor antagonist DU-125530 using receptor autoradiography, intracerebral microdialysis and electrophysiological recordings. Its capacity to accelerate/enhance the clinical effects of fluoxetine was assessed in a double-blind, randomized, 6 week placebo-controlled trial in 50 patients with major depression (clinicaltrials.gov identifier NCT01119430). KEY
resultsDU-125530 showed equal (low nM) potency to displace agonist and antagonist binding to pre- and post-synaptic 5-HT(1A) receptors in rat and human brain. It antagonized suppression of 5-hydroxytryptaminergic activity evoked by 8-OH-DPAT and SSRIs in vivo. DU-125530 augmented SSRI-induced increases in extracellular 5-HT as effectively as in mice lacking 5-HT(1A) receptors, indicating a silent, maximal occupancy of pre-synaptic 5-HT(1A) receptors at the dose used. However, DU-125530 addition to fluoxetine did not accelerate nor augment its antidepressant effects. CONCLUSIONS AND IMPLICATIONS: DU-125530 is an excellent pre- and post-synaptic 5-HT(1A) receptor antagonist. However, blockade of post-synaptic 5- HT(1A) receptors by DU-125530 cancels benefits obtained by enhancing pre-synaptic 5-hydroxytryptaminergic function.
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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.