ArticleBMC neurology2018
Highly selective SGLT2 inhibitor dapagliflozin reduces seizure activity in pentylenetetrazol-induced murine model of epilepsy.
Article in BMC neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Newer glucose-lowering drugs reduce the risk of late-onset seizure and epilepsy: A meta-analysis.Epilepsia open · 2024Pooled it
- Anti-diabetic medications to fight Parkinson's disease and dementia with Lewy bodies: a pilot study.Frontiers in neurologyTrial
- Protective effect of dapagliflozin against phenytoin-induced cerebellar dysfunction and histological alterations in rats: the role of SIRT1/Nrf2/HO-1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Plant-derived Natural Products in Neurological and Psychiatric Disorders: Mechanisms of Action and Synergistic Roles with Probiotics.Molecular neurobiology · 2026Review
- Sodium-glucose cotransporter 2 inhibitors and the risk of late onset epilepsy: A real-world cohort study.Epilepsia · 2026Article
- SGLT2 Inhibitors in Alzheimer's Disease: Biochemical Insights and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Targeting neuroinflammatory pathways in epilepsy: a combined network-pharmacology and in vivo study of dapagliflozin and ticagrelor.Inflammopharmacology · 2025Article
- Sodium-Glucose Cotransporter-2 Inhibitors in Diabetes and Beyond: Mechanisms, Pleiotropic Benefits, and Clinical Use-Reviewing Protective Effects Exceeding Glycemic Control.Molecules (Basel, Switzerland) · 2025Review
- Effects of Two Boron-Containing Compounds Structurally Related to Topiramate on Three Models of Drug-Induced Seizures in Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- TLR-4/Notch1/NF-κB pathway modulation by dapagliflozin: a novel mechanism for neuroprotection in hepatic encephalopathy.Metabolic brain disease · 2025Article
- Cognitive Dysfunction and Dementia in Type 2 Diabetes Mellitus: Insights into Mechanisms, Models, and Therapeutics.ACS pharmacology & translational science · 2025Review
- Empagliflozin Inhibits Neuronal Ferroptosis Induced by Oxygen-Glucose Deprivation/Reoxygenation by Activating the Nrf2/HO-1 Pathway.Molecular neurobiology · 2025Article
- Adverse Drug Reactions to SGLT2i Reported by Type 2 Diabetes New Users: An Active Surveillance Study.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Empagliflozin Mitigates PTZ-Induced Seizures in Rats: Modulating Npas4 and CREB-BDNF Signaling Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Multi-dimensional roles of sodium-glucose cotransporter 2 inhibitors: beyond hypoglycemic and cardiorenal protection.Frontiers in endocrinology · 2025Review
- Repurposing Dapagliflozin for Mitigation of the Kidney Injury Triggered by Cadmium in Rats: Role of Autophagy, Apoptosis, and the SIRT1/Nrf2/HO-1 Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Genetic Variation in Targets of Antidiabetic Drugs and Amyotrophic Lateral Sclerosis Risk.Biomedicines · 2024Article
- SGLT2 and SGLT1 inhibitors suppress the activities of the RVLM neurons in newborn Wistar rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Targeting Autophagy, Apoptosis, and Oxidative Perturbations with Dapagliflozin Mitigates Cadmium-Induced Cognitive Dysfunction in Rats.Biomedicines · 2023Article
- Stimulation of Autophagy by Dapagliflozin Mitigates Cadmium-Induced Testicular Dysfunction in Rats: The Role of AMPK/mTOR and SIRT1/Nrf2/HO-1 Pathways.Pharmaceuticals (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWorldwide, over 10 million individuals suffer from drug-resistant epilepsy. New therapeutic strategies are needed to address this debilitating disease. Inhibition of sodium-glucose linked transporters (SGLTs), which are variably expressed in the brain, has been demonstrated to reduce seizure activity in murine models of epilepsy. Here we investigated the effects of dapagliflozin, a highly competitive SGLT2 inhibitor currently used as a drug for diabetes mellitus, on seizure activity in rats with pentylenetetrazol (PTZ) induced seizures.
methodsLaboratory rats (n = 48) were evenly randomized into two experiments, each with four study arms: (1) a vehicle-treated (placebo) arm infused with saline; (2) a control arm infused with PTZ; (3) a treatment arm with PTZ and dapagliflozin at 75 mg/kg, and (4) another treatment arm with PTZ and dapagliflozin at 150 mg/kg. Study subjects were assessed for seizures either via EEG as measured by spike wave percentage (SWP), or clinically via Racine's scales scores (RSS) and time to first myoclonic jerk (TFMJ).
resultsRats treated with dapagliflozin had lower mean SWP on EEG (20.4% versus 75.3% for untreated rats). Behaviorally, treatment with dapagliflozin improved means RSS (2.33 versus 5.5) and mean TFMJ (68.3 versus 196.7 s). All of these findings were statistically significant with p-values of < 0.0001. There was a trend towards even better seizure control with the higher dose of dapagliflozin at 150 mg/kg, however this was not consistently statistically significant.
conclusionsDapagliflozin decreased seizure activity in rats with PTZ-induced seizures. This may be explained by the anti-seizure effects of decreased glucose availability and a reduction in sodium transport across neuronal membranes which can confer a stabilizing effect against excitability and unwanted depolarization. The potential clinical role of dapagliflozin and other SGLT2 inhibitors as anti-seizure medications should be further explored.
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