The persistent Na+ current (INaP) has been proposed as the putative target of the anti-absence antiepileptic drugs. Accordingly, the effect of reference anti-absence drugs ethosuximide (ESM) and valproate (VPA), and of the new antiepileptic drug levetiracetam (LEV), on INaP have been tested in CA1 hippocampal neurons and compared to the classic anticonvulsant phenytoin (PHT) and the neuroprotective agent riluzole (RIL). Whole-cell patch-clamp recordings of the slowly inactivating current, fully characterized as INaP, were performed with a standard voltage-step protocol on thin hippocampal slices prepared from rat brain. Both PHT (100 microM) and RIL (10 microM) strongly depressed INaP, whereas ESM (1 mM) induced a slight decrease of INaP and VPA (1 mM) had no effect. Likewise, 60-min perfusion with relevant concentrations of LEV (10, 32 or 100 microM) did not modify INaP. In conclusion, these data question the impact of INaP depression as an anti-absence mechanism, and also disclaim the involvement of INaP in the antiepileptic mechanism of LEV.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/00001756-200404290-00023 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Alpha-2a adrenergic receptor activation in genetic absence epilepsy: An absence status model?
Epilepsia Open
April 2024
Department of Medical Pharmacology, School of Medicine, Marmara University, Istanbul, Turkey.
Objective: The objective of the study was to propose a candidate animal model of absence status epilepticus induced by specific alpha-2a adrenergic receptor (α2AR) activation. We also aim to investigate the responsiveness of this model to classical anti-status or anti-absence medications.
Methods: An α2AR agonist, dexmedetomidine (DEX), was injected intracerebroventricularly into adult rats with genetic absence epilepsy, and their electroencephalography (EEG) was recorded.
An In Vivo Electroencephalographic Analysis of the Effect of Riluzole against Limbic and Absence Seizure and Comparison with Glutamate Antagonists.
Pharmaceutics
July 2023
Section of Pharmacology, Science of Health Department, School of Medicine, University "Magna Graecia" of Catanzaro, 88100 Catanzaro, Italy.
Background: Riluzole (RLZ) has demonstrated neuroprotective effects in several neurological disorders. These neuroprotective effects seem to be mainly due to its ability to inhibit the excitatory glutamatergic neurotransmission, acting on different targets located both at the presynaptic and postsynaptic levels.
Methods: In the present study, we evaluated the effects of Riluzole (RLZ) against limbic seizures, induced by AMPA, kainate, and NMDA receptor agonists in Sprague-Dawley rats, and in a well-validated genetic model of absence epilepsy, the WAG/Rij rat.
The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.
IBRO Neurosci Rep
December 2022
Donders Institute for Brain, Cognition, and Behavior, Donders Center for Cognition, Radboud University, Nijmegen, PO Box 9104, 6500 HE Nijmegen, the Netherlands.
This review discusses the long-term effects of early-life environment on epileptogenesis, epilepsy, and neuropsychiatric comorbidities with an emphasis on the absence epilepsy. The WAG/Rij rat strain is a well-validated genetic model of absence epilepsy with mild depression-like (dysthymia) comorbidity. Although pathologic phenotype in WAG/Rij rats is genetically determined, convincing evidence presented in this review suggests that the absence epilepsy and depression-like comorbidity in WAG/Rij rats may be governed by early-life events, such as prenatal drug exposure, early-life stress, neonatal maternal separation, neonatal handling, maternal care, environmental enrichment, neonatal sensory impairments, neonatal tactile stimulation, and maternal diet.
View Article and Find Full Text PDFThe Orexin System: A Potential Player in the Pathophysiology of Absence Epilepsy.
Curr Neuropharmacol
June 2022
Donders Centre for Cognition, Radboud University, Nijmegen, The Netherlands.
Background: Absence epilepsy is characterized by the presence of spike-and-wave discharges (SWDs) at the EEG generated within the cortico-thalamo-cortical circuit. The molecular mechanisms involved in the pathophysiology of absence epilepsy are only partially known. WAG/Rij rats older than 2-3 months develop spontaneous SWDs, and they are sensitive to anti- absence medications.
View Article and Find Full Text PDFChemogenetic Activation of Feed-Forward Inhibitory Parvalbumin-Expressing Interneurons in the Cortico-Thalamocortical Network During Absence Seizures.
Front Cell Neurosci
May 2021
Department of Anatomy, School of Biomedical Sciences, Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
Parvalbumin-expressing (PV+) interneurons are a subset of GABAergic inhibitory interneurons that mediate feed-forward inhibition (FFI) within the cortico-thalamocortical (CTC) network of the brain. The CTC network is a reciprocal loop with connections between cortex and thalamus. FFI PV+ interneurons control the firing of principal excitatory neurons within the CTC network and prevent runaway excitation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!