Trial reportTranslational psychiatry2022
Central nervous system effects of TAK-653, an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptor (AMPAR) positive allosteric modulator in healthy volunteers.
Trial report in Translational psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Depressive disorders: systematic review of approved psychiatric medications (2009-April 2025) and pipeline phase 3 medications.BMC psychiatry · 2025Pooled it
- Sustained pharmacodynamic effects of S-ketamine on cortical excitability and resting-state brain activity: A randomized, placebo-controlled trial.British journal of clinical pharmacology · 2026Trial
- A novel psychedelic 5-HTJournal of psychopharmacology (Oxford, England) · 2026Trial
- Effects of the selective AMPA modulator NBI-1065845 on the pharmacokinetics of midazolam or ethinyl estradiol-levonorgestrel in healthy adults.Clinical and translational science · 2024Trial
- AMPA receptor modulation in depression: from molecular mechanisms of plasticity to therapeutic translation.Pharmacological reports : PR · 2026Review
- Ascorbic acid enhances antidepressant-like efficacy of esketamine: Hippocampal TARP-γ8-containing AMPA receptors mediate synaptic modulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Advancing past ketamine: emerging glutamatergic compounds for the treatment of depression.European archives of psychiatry and clinical neuroscience · 2025Review
- Positive AMPA and Kainate Receptor Modulators and Their Therapeutic Potential in CNS Diseases: A Comprehensive Review.International journal of molecular sciences · 2025Review
- TAK-653 Reverses Core Depressive Symptoms in Chronic Stress-Induced Monkey Model.Biomedicines · 2025Article
- Amplification of the therapeutic potential of AMPA receptor potentiators from the nootropic era to today.Pharmacology, biochemistry, and behavior · 2025Review
- Review
- AMPA receptors play an important role in the biological consequences of spinal cord injury: Implications for AMPA receptor modulators for therapeutic benefit.Biochemical pharmacology · 2024Review
- Depression clinical trials worldwide: a systematic analysis of the ICTRP and comparison with ClinicalTrials.gov.Translational psychiatry · 2024Review
- Potentiation of AMPA receptors for rapid therapeutic gain in psychiatry has reached a new level of excitement.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Emerging trends in antipsychotic and antidepressant drug development: Targeting nonmonoamine receptors and innovative mechanisms.PCN reports : psychiatry and clinical neurosciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TAK-653 is a novel AMPA receptor positive allosteric modulator in clinical development for the treatment of major depressive disorder (MDD). This study aimed to measure the functional pharmacodynamic central nervous system (CNS) effects of TAK-653. A randomised, double-blind, placebo-controlled, three-way crossover (placebo, TAK-653 0.5 mg and 6 mg) study with 24 healthy volunteers was performed. NeuroCart tests consisting of body sway (BS), saccadic peak velocity (SPV), smooth pursuit eye movements (SP), adaptive tracking (AT), Bowdle and Bond and Lader Visual Analogue Scales (B-VAS and BL-VAS) and Stroop test were performed pre-dose and 3.5 and 4 h post-dose. Data were analysed using a mixed model analysis of covariance with baseline as covariate. It was found that TAK-653 did not affect BS and subjective drug effects as measured by B-VAS and BL-VAS at either dose level. TAK-653 0.5 mg increased SPV (degrees/second) (19.49 [5.98, 32.99], P = 0.02) and affected Stroop difference in reaction time between correct congruent and correct incongruent answers and number of correct responses in incongruent trials (22.0 [4.0, 40.0], P = 0.05 and -0.3 [-0.5, -0.1], P = 0.02, respectively). TAK-653 6 mg improved AT (%) (1.68 [0.51, 2.84], P = 0.02) and increased SPV (degrees/s) (15.40 [1.91, 28.90], P = 0.06) and SP (%) (2.32 [0.37, 4.27], P = 0.05). Based on these findings it can be concluded that TAK-653 demonstrated a psychostimulant-like pharmacodynamic profile on the NeuroCart consistent with previously reported increase of cortical excitability following Transcranial Magnetic Stimulation (TMS) of the human motor cortex.
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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.