ArticleThe Journal of experimental medicine2004
Clinically approved heterocyclics act on a mitochondrial target and reduce stroke-induced pathology.
Article in The Journal of experimental medicine, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 97 citations in OpenAlex.
- Neuroprotective Effects of Phenothiazines on Acute Ischemic Stroke.CNS neuroscience & therapeutics · 2026Review
- The MT1 receptor as the target of ramelteon neuroprotection in ischemic stroke.Journal of pineal research · 2024Article
- Chlorpromazine and Promethazine (C+P) Reduce Brain Injury after Ischemic Stroke through the PKC-Mediators of inflammation · 2022Article
- Inhibition of eIF5A hypusination pathway as a new pharmacological target for stroke therapy.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Rasagiline and selegiline modulate mitochondrial homeostasis, intervene apoptosis system and mitigate α-synuclein cytotoxicity in disease-modifying therapy for Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2020Review
- Reduced Apoptotic Injury by Phenothiazine in Ischemic Stroke through the NOX-Akt/PKC Pathway.Brain sciences · 2019Article
- Efficacy of Aerosolized Rifaximin versus Tobramycin for Treatment of Pseudomonas aeruginosa Pneumonia in Mice.Antimicrobial agents and chemotherapy · 2019Article
- Systematic Identification of MCU Modulators by Orthogonal Interspecies Chemical Screening.Molecular cell · 2017Article
- Phenothiazines Enhance Mild Hypothermia-induced Neuroprotection via PI3K/Akt Regulation in Experimental Stroke.Scientific reports · 2017Article
- The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology.Physiological reviews · 2015Review
- Qualitative characterization of the rat liver mitochondrial lipidome using all ion fragmentation on an Exactive benchtop Orbitrap MS.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Of mice and men: modelling post-stroke depression experimentally.British journal of pharmacology · 2014Review
- Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models.Nature chemical biology · 2014Article
- Therapeutic neuroprotective agents for amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2013Review
- Dietary macronutrients modulate the fatty acyl composition of rat liver mitochondrial cardiolipins.Journal of lipid research · 2013Article
- Qualitative Characterization of the Rat Liver Mitochondrial Lipidome using LC-MS Profiling and High Energy Collisional Dissociation (HCD) All Ion Fragmentation.Metabolomics : Official journal of the Metabolomic Society · 2013Article
- A cell-based fascin bioassay identifies compounds with potential anti-metastasis or cognition-enhancing functions.Disease models & mechanisms · 2013Article
- Separation of cis-trans phospholipid isomers using reversed phase LC with high resolution MS detection.Analytical chemistry · 2012Article
- New drug targets in depression: inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates--Nrf2 activators and GSK-3 inhibitors.Inflammopharmacology · 2012Review
- Impaired mitochondrial function in psychiatric disorders.Nature reviews. Neuroscience · 2012Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Substantial evidence indicates that mitochondria are a major checkpoint in several pathways leading to neuronal cell death, but discerning critical propagation stages from downstream consequences has been difficult. The mitochondrial permeability transition (mPT) may be critical in stroke-related injury. To address this hypothesis, identify potential therapeutics, and screen for new uses for established drugs with known toxicity, 1,040 FDA-approved drugs and other bioactive compounds were tested as potential mPT inhibitors. We report the identification of 28 structurally related drugs, including tricyclic antidepressants and antipsychotics, capable of delaying the mPT. Clinically achievable doses of one drug in this general structural class that inhibits mPT, promethazine, were protective in both in vitro and mouse models of stroke. Specifically, promethazine protected primary neuronal cultures subjected to oxygen-glucose deprivation and reduced infarct size and neurological impairment in mice subjected to middle cerebral artery occlusion/reperfusion. These results, in conjunction with new insights provided to older studies, (a) suggest a class of safe, tolerable drugs for stroke and neurodegeneration; (b) provide new tools for understanding mitochondrial roles in neuronal cell death; (c) demonstrate the clinical/experimental value of screening collections of bioactive compounds enriched in clinically available agents; and (d) provide discovery-based evidence that mPT is an essential, causative event in stroke-related injury.
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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.