ArticleTranslational psychiatry2013
Latrepirdine is a potent activator of AMP-activated protein kinase and reduces neuronal excitability.
Article in Translational psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Elevation in plasma tRNA fragments precede seizures in human epilepsy.The Journal of clinical investigation · 2019Trial
- Mitochondrial and Antioxidant Activity as the Basis of the Neuroprotective Effect of Potential Multitarget Drugs for the Treatment of Neurodegenerative Diseases.Current neuropharmacology · 2026Review
- Latrepirdine (Dimebon), a potent 5-HTFrontiers in pharmacology · 2026Article
- Ketone body β-hydroxybutyrate (BHB) preserves mitochondrial bioenergetics.Scientific reports · 2023Article
- A bioisostere of Dimebon/Latrepirdine delays the onset and slows the progression of pathology in FUS transgenic mice.CNS neuroscience & therapeutics · 2021Article
- Review
- AMP-activated protein kinase slows D2 dopamine autoreceptor desensitization in substantia nigra neurons.Neuropharmacology · 2019Article
- Involvement of AMP-activated protein kinase in neuroinflammation and neurodegeneration in the adult and developing brain.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2019Review
- Mitochondria as Potential Targets in Alzheimer Disease Therapy: An Update.Frontiers in pharmacology · 2019Review
- In Vitro Effects of Cognitives and Nootropics on Mitochondrial Respiration and Monoamine Oxidase Activity.Molecular neurobiology · 2017Article
- Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine).Molecular neurobiology · 2015Review
- A dual role for AMP-activated protein kinase (AMPK) during neonatal hypoxic-ischaemic brain injury in mice.Journal of neurochemistry · 2015Article
- Advances in recent patent and clinical trial drug development for Alzheimer's disease.Pharmaceutical patent analyst · 2014Review
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Latrepirdine/Dimebon is a small-molecule compound with attributed neurocognitive-enhancing activities, which has recently been tested in clinical trials for the treatment of Alzheimer's and Huntington's disease. Latrepirdine has been suggested to be a neuroprotective agent that increases mitochondrial function, however the molecular mechanisms underlying these activities have remained elusive. We here demonstrate that latrepirdine, at (sub)nanomolar concentrations (0.1 nM), activates the energy sensor AMP-activated protein kinase (AMPK). Treatment of primary neurons with latrepirdine increased intracellular ATP levels and glucose transporter 3 translocation to the plasma membrane. Latrepirdine also increased mitochondrial uptake of the voltage-sensitive probe TMRM. Gene silencing of AMPKα or its upstream kinases, LKB1 and CaMKKβ, inhibited this effect. However, studies using the plasma membrane potential indicator DisBAC2(3) demonstrated that the effects of latrepirdine on TMRM uptake were largely mediated by plasma membrane hyperpolarization, precluding a purely 'mitochondrial' mechanism of action. In line with a stabilizing effect of latrepirdine on plasma membrane potential, pretreatment with latrepirdine reduced spontaneous Ca(2+) oscillations as well as glutamate-induced Ca(2+) increases in primary neurons, and protected neurons against glutamate toxicity. In conclusion, our experiments demonstrate that latrepirdine is a potent activator of AMPK, and suggest that one of the main pharmacological activities of latrepirdine is a reduction in neuronal excitability.
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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.