ReviewBiological psychiatry2013
Antidepressant effects of the muscarinic cholinergic receptor antagonist scopolamine: a review.
Review in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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
79 citing papers in PubMed, 191 citations in OpenAlex.
- Group-Based Symptom Trajectory of Intramuscular Administration of Scopolamine Augmentation in Moderate to Severe Major Depressive Disorder: A Post-Hoc Analysis.Neuropsychiatric disease and treatment · 2023Trial
- Neurophysiological Changes Associated with Antidepressant Response to Ketamine Not Observed in a Negative Trial of Scopolamine in Major Depressive Disorder.The international journal of neuropsychopharmacology · 2019Trial
- Fabrication and efficacy evaluation of scopolamine-loaded dissolving microneedle for rapid antidepressant therapy.International journal of pharmaceutics: X · 2026Article
- Comparing affective bias modification by first- and second-generation antidepressants in male rats using a translational behavioural task.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Scopolamine Prevents Mitochondrial Dysfunction in Depressive Disorder, Potentially via Its Anti-Inflammatory Effects.Journal of inflammation research · 2026Article
- Scopolamine exerted antidepressant-like behavioral effects via restoring the synaptic plasticity in CRS-treated mice.Metabolic brain disease · 2025Article
- Dopaminergic Perturbation in the Aetiology of Neurodevelopmental Disorders.Molecular neurobiology · 2025Review
- Subchronic administration of scopolamine reverses UCMS-induced behavior in mice via eEF2 protein dephosphorylation.Pharmacological reports : PR · 2024Article
- Septohippocampal cholinergic system at the intersection of stress and cognition: Current trends and translational implications.The European journal of neuroscience · 2024Review
- Rapid-acting antidepressant drugs modulate affective bias in rats.Science translational medicine · 2024Article
- Depression and the Glutamate/GABA-Glutamine Cycle.Current neuropharmacology · 2024Review
- Approaches for Increasing Cerebral Efflux of Amyloid-β in Experimental Systems.Journal of Alzheimer's disease : JAD · 2024Review
- mGlu2/3 receptor antagonists for depression: overview of underlying mechanisms and clinical development.European archives of psychiatry and clinical neuroscience · 2023Review
- HCN channel inhibitor induces ketamine-like rapid and sustained antidepressant effects in chronic social defeat stress model.Neurobiology of stress · 2023Article
- Are mGluR2/3 Inhibitors Potential Compounds for Novel Antidepressants?Cellular and molecular neurobiology · 2023Review
- Basal Forebrain Cholinergic Innervation Induces Depression-Like Behaviors Through Ventral Subiculum Hyperactivation.Neuroscience bulletin · 2023Article
- Tear film instability is associated with weakened colocalization between occludin and MUC5AC in scopolamine-induced dry eye disease (DED) rats.International ophthalmology · 2023Article
- TIAM1-mediated synaptic plasticity underlies comorbid depression-like and ketamine antidepressant-like actions in chronic pain.The Journal of clinical investigation · 2022Article
- Rapid antidepressant-like effects of muscarinic receptor antagonists require BDNF-dependent signaling in the ventrolateral periaqueductal gray.Psychopharmacology · 2022Article
- Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs.Molecular psychiatry · 2022Article
19 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
3 authors at 1 institution in 1 country.
Funding
Abstract
The muscarinic cholinergic receptor system has been implicated in the pathophysiology of depression, with physiological evidence indicating this system is overactive or hyperresponsive in depression and with genetic evidence showing that variation in genes coding for receptors within this system are associated with higher risk for depression. In studies aimed at assessing whether a reduction in muscarinic cholinergic receptor function would improve depressive symptoms, the muscarinic receptor antagonist scopolamine manifested antidepressant effects that were robust and rapid relative to conventional pharmacotherapies. Here, we review the data from a series of randomized, double-blind, placebo-controlled studies involving subjects with unipolar or bipolar depression treated with parenteral doses of scopolamine. The onset and duration of the antidepressant response are considered in light of scopolamine's pharmacokinetic properties and an emerging literature that characterizes scopolamine's effects on neurobiological systems beyond the cholinergic system that appear relevant to the neurobiology of mood disorders. Scopolamine infused at 4.0 μg/kg intravenously produced robust antidepressant effects versus placebo, which were evident within 3 days after the initial infusion. Placebo-adjusted remission rates were 56% and 45% for the initial and subsequent replication studies, respectively. While effective in male and female subjects, the change in depression ratings was greater in female subjects. Clinical improvement persisted more than 2 weeks following the final infusion. The timing and persistence of the antidepressant response to scopolamine suggest a mechanism beyond that of direct muscarinic cholinergic antagonism. These temporal relationships suggest that scopolamine-induced changes in gene expression and synaptic plasticity may confer the therapeutic mechanism.
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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.