ArticleBrain research2014
The multi-functional drug tropisetron binds APP and normalizes cognition in a murine Alzheimer's model.
Article in Brain research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- One-day tropisetron treatment improves cognitive deficits and P50 inhibition deficits in schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- Trial
- Serotonergic System Dysregulation in Alzheimer's Disease.ACS chemical neuroscience · 2026Review
- Discovery of an APP-selective BACE1 inhibitor for Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Targeting the serotonergic system in the treatment of neurodegenerative diseases-emerging therapies and unmet challenges.Pharmacological reviews · 2025Review
- Tropisetron Suppresses Chronic Pancreatitis and Pancreatic Cancer by Blocking Interleukin 33 Expression.Cancers · 2025Article
- Characterization of the Molecular Mechanisms Underlying Lurasidone-Induced Acute Manic Episodes in Bipolar Depression: A Network Pharmacology and Molecular Docking Approach.CNS neuroscience & therapeutics · 2025Article
- Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion.Nature chemical biology · 2025Article
- Serotonin 3 receptor antagonism reduces angiotensin II-induced abdominal aortic aneurysms: Contribution of periaortic fat-derived serotonin.The Journal of pharmacology and experimental therapeutics · 2025Article
- Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease.Neural regeneration research · 2023Article
- Intraoperative 5-HTJournal of anesthesia · 2023Article
- Article
- Cholinergic regulation of object recognition memory.Frontiers in behavioral neuroscience · 2022Review
- 5-HTPerioperative medicine (London, England) · 2021Article
- Deconstructing Alzheimer's Disease: How to Bridge the Gap between Experimental Models and the Human Pathology?International journal of molecular sciences · 2021Review
- Tropisetron But Not Granisetron Ameliorates Spatial Memory Impairment Induced by Chronic Cerebral Hypoperfusion.Neurochemical research · 2020Article
- Effect of Tropisetron on Prevention of Emergence Delirium in Patients After Noncardiac Surgery: A Trial Protocol.JAMA network open · 2020Article
- Recent Expansions on Cellular Models to Uncover the Scientific Barriers Towards Drug Development for Alzheimer's Disease.Cellular and molecular neurobiology · 2019Review
- Granisetron Alleviates Alzheimer's Disease Pathology in TgSwDI Mice Through Calmodulin-Dependent Protein Kinase II/cAMP-Response Element Binding Protein Pathway.Journal of Alzheimer's disease : JAD · 2019Article
- A small molecule ApoE4-targeted therapeutic candidate that normalizes sirtuin 1 levels and improves cognition in an Alzheimer's disease mouse model.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Tropisetron was identified in a screen for candidates that increase the ratio of the trophic, neurite-extending peptide sAPPα to the anti-trophic, neurite-retractive peptide Aβ, thus reversing this imbalance in Alzheimer's disease (AD). We describe here a hierarchical screening approach to identify such drug candidates, moving from cell lines to primary mouse hippocampal neuronal cultures to in vivo studies. By screening a clinical compound library in the primary assay using CHO-7W cells stably transfected with human APPwt, we identified tropisetron as a candidate that consistently increased sAPPα. Secondary assay testing in neuronal cultures from J20 (PDAPP, huAPP(Swe/Ind)) mice showed that tropisetron consistently increased the sAPPα/Aβ 1-42 ratio. In in vivo studies in J20 mice, tropisetron improved the sAPPα/Aβ ratio along with spatial and working memory in mice, and was effective both during the symptomatic, pre-plaque phase (5-6 months) and in the late plaque phase (14 months). This ameliorative effect occurred at a dose of 0.5mg/kg/d (mkd), translating to a human-equivalent dose of 5mg/day, the current dose for treatment of postoperative nausea and vomiting (PONV). Although tropisetron is a 5-HT3 receptor antagonist and an α7nAChR partial agonist, we found that it also binds to the ectodomain of APP. Direct comparison of tropisetron to the current AD therapeutics memantine (Namenda) and donepezil (Aricept), using similar doses for each, revealed that tropisetron induced greater improvements in memory and the sAPPα/Aβ1-42 ratio. The improvements observed with tropisetron in the J20 AD mouse model, and its known safety profile, suggest that it may be suitable for transition to human trials as a candidate therapeutic for mild cognitive impairment (MCI) and AD, and therefore it has been approved for testing in clinical trials beginning in 2014.
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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.