ArticleNeuroscience letters2008
Levetiracetam inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture.
Article in Neuroscience letters, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 80 citations in OpenAlex.
- The Impact of Levetiracetam on Various Symptoms of Morphine Dependence in Mice.Life (Basel, Switzerland) · 2026Article
- Pharmacological reduction of reverse-translated hippocampal hyperactivity in mouse: relevance for psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Neuronal Mitochondrial Calcium Uniporter (MCU) Deficiency Is Neuroprotective in Hyperexcitability by Modulation of Metabolic Pathways and ROS Balance.Molecular neurobiology · 2024Article
- Effect of Levetiracetam on Oxidant-Antioxidant Activity during Long-Term Temporal Lobe Epilepsy in Rats.International journal of molecular sciences · 2024Article
- Changes in the Dentate Gyrus Gene Expression Profile Induced by Levetiracetam Treatment in Rats with Mesial Temporal Lobe Epilepsy.International journal of molecular sciences · 2024Article
- Traditional and Innovative Anti-seizure Medications Targeting Key Physiopathological Mechanisms: Focus on Neurodevelopment and Neurodegeneration.Current neuropharmacology · 2023Article
- The genotype-phenotype correlations of theFrontiers in molecular neuroscience · 2023Article
- Levetiracetam Mechanisms of Action: From Molecules to Systems.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Case Report: Developmental Delay and Acute Neuropsychiatric Episodes Associated With aFrontiers in pharmacology · 2022Article
- Combined Pharmacophore and Grid-Independent Molecular Descriptors (GRIND) Analysis to Probe 3D Features of Inositol 1,4,5-Trisphosphate Receptor (IPInternational journal of molecular sciences · 2021Article
- Levetiracetam treatment leads to functional recovery after thoracic or cervical injuries of the spinal cord.NPJ Regenerative medicine · 2021Article
- AEpilepsy & behavior reports · 2021Article
- Intramuscular atenolol and levetiracetam reduce mortality in a rat model of paraoxon-induced status epilepticus.Annals of the New York Academy of Sciences · 2020Article
- Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update.Journal of clinical medicine · 2020Review
- Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?Epilepsia · 2020Review
- Calcium Hypothesis of Gulf War Illness: Role of Calcium Ions in Neurological Morbidities in a DFP-Based Rat Model for Gulf War Illness.Neuroscience insights · 2020Review
- Targeting Intracellular Calcium Stores Alleviates Neurological Morbidities in a DFP-Based Rat Model of Gulf War Illness.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- GABA Regulation of Burst Firing in Hippocampal Astrocyte Neural Circuit: A Biophysical Model.Frontiers in cellular neuroscience · 2019Article
- Effects of levetiracetam on astroglial release of kynurenine-pathway metabolites.British journal of pharmacology · 2018Article
- Trkb-IP3 Pathway Mediating Neuroprotection in Rat Hippocampal Neuronal Cell Culture Following Induction of Kainic Acid.The Malaysian journal of medical sciences : MJMS · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Epilepsy affects approximately 1% of the population worldwide, and there is a pressing need to develop new anti-epileptic drugs (AEDs) and understand their mechanisms of action. Levetiracetam (LEV) is a novel AED and despite its increasingly widespread clinical use, its mechanism of action is as yet undetermined. Intracellular calcium ([Ca2+]i) regulation by both inositol 1,4,5-triphosphate receptors (IP3R) and ryanodine receptors (RyR) has been implicated in epileptogenesis and the maintenance of epilepsy. To this end, we investigated the effect of LEV on RyR and IP3R activated calcium-induced calcium release (CICR) in hippocampal neuronal cultures. RyR-mediated CICR was stimulated using the well-characterized RyR activator, caffeine. Caffeine (10mM) caused a significant increase in [Ca2+]i in hippocampal neurons. Treatment with LEV (33 microM) prior to stimulation of RyR-mediated CICR by caffeine led to a 61% decrease in the caffeine induced peak height of [Ca2+]i when compared to the control. Bradykinin stimulates IP3R-activated CICR-to test the effect of LEV on IP3R-mediated CICR, bradykinin (1 microM) was used to stimulate cells pre-treated with LEV (100 microM). The data showed that LEV caused a 74% decrease in IP3R-mediated CICR compared to the control. In previous studies we have shown that altered Ca2+ homeostatic mechanisms play a role in seizure activity and the development of spontaneous recurrent epileptiform discharges (SREDs). Elevations in [Ca2+]i mediated by CICR systems have been associated with neurotoxicity, changes in neuronal plasticity, and the development of AE. Thus, the ability of LEV to modulate the two major CICR systems demonstrates an important molecular effect of this agent on a major second messenger system in neurons.
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Registered trials
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