ArticleEpilepsia2021
Systemic administration of ivabradine, a hyperpolarization-activated cyclic nucleotide-gated channel inhibitor, blocks spontaneous absence seizures.
Article in Epilepsia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- The Contribution of HCN Channelopathies in Different Epileptic Syndromes, Mechanisms, Modulators, and Potential Treatment Targets: A Systematic Review.Frontiers in molecular neuroscience · 2022Pooled it
- Developmental and cell type-specific contributions of thalamic serotonin 2A receptors to absence seizures.Epilepsia · 2026Article
- Roles of funny HCN.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2025Review
- The role of HCN channels on the effects of T-type calcium channels and GABAPflugers Archiv : European journal of physiology · 2024Article
- Opioid-Induced Hyperalgesia and Tolerance Are Driven by HCN Ion Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- An anchor-tether 'hindered' HCN1 inhibitor is antihyperalgesic in a rat spared nerve injury neuropathic pain model.British journal of anaesthesia · 2023Article
- cAMP-mediated upregulation of HCN channels in VTA dopamine neurons promotes cocaine reinforcement.Molecular psychiatry · 2023Article
- Thalamocortical circuits in generalized epilepsy: Pathophysiologic mechanisms and therapeutic targets.Neurobiology of disease · 2023Review
- The Impact of Altered HCN1 Expression on Brain Function and Its Relationship with Epileptogenesis.Current neuropharmacology · 2023Review
- Bibliometric analysis of hyperpolarization-activated cyclic nucleotide-gated (HCN)channels research (2004-2020).Channels (Austin, Tex.) · 2022Article
- Discrete subicular circuits control generalization of hippocampal seizures.Nature communications · 2022Article
- Effects of Antiarrhythmic Drugs on Antiepileptic Drug Action-A Critical Review of Experimental Findings.International journal of molecular sciences · 2022Review
- Differential Serotonergic Modulation of Principal Neurons and Interneurons in the Anterior Piriform Cortex.Frontiers in neuroanatomy · 2022Article
- The Bradycardic Agent Ivabradine Acts as an Atypical Inhibitor of Voltage-Gated Sodium Channels.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 5 countries.
Funding
Abstract
objectiveHyperpolarization-activated cyclic nucleotide-gated (HCN) channels are known to be involved in the generation of absence seizures (ASs), and there is evidence that cortical and thalamic HCN channel dysfunctions may have a proabsence role. Many HCN channel blockers are available, but their role in ASs has been investigated only by localized brain injection or in in vitro model systems due to their limited brain availability. Here, we investigated the effect on ASs of orally administered ivabradine (an HCN channel blocker approved for the treatment of heart failure in humans) following injection of the P-glycoprotein inhibitor elacridar, which is known to increase penetration into the brain of drug substrates for this efflux transporter. The action of ivabradine was also tested following in vivo microinjection into the cortical initiation network (CIN) of the somatosensory cortex and in the thalamic ventrobasal nucleus (VB) as well as on cortical and thalamocortical neurons in brain slices.
methodsWe used electroencephalographic recordings in freely moving Genetic Absence Epilepsy Rats From Strasbourg (GAERSs) to assess the action of oral administration of ivabradine, with and without elacridar, on ASs. Ivabradine was also microinjected into the CIN and VB of GAERSs in vivo and applied to Wistar CIN and GAERS VB slices while recording patch-clamped cortical Layer 5/6 and thalamocortical neurons, respectively.
resultsOral administration of ivabradine markedly and dose-dependently reduced ASs. Ivabradine injection into CIN abolished ASs and elicited small-amplitude 4-7-Hz waves (without spikes), whereas in the VB it was less potent. Moreover, ivabradine applied to GAERS VB and Wistar CIN slices selectively decreased HCN channel-dependent properties of cortical Layer 5/6 pyramidal and thalamocortical neurons, respectively. SIGNIFICANCE: These results provide the first demonstration of the antiabsence action of a systemically administered HCN channel blocker, indicating the potential of this class of drugs as a novel therapeutic avenue for ASs.
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