ArticleBritish journal of pharmacology2013
ONO-2506 inhibits spike-wave discharges in a genetic animal model without affecting traditional convulsive tests via gliotransmission regulation.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Calcium channelopathies and intellectual disability: a systematic review.Orphanet journal of rare diseases · 2021Pooled it
- Emerging Role of Tripartite Synaptic Transmission in the Pathomechanism of Autosomal-Dominant Sleep-Related Hypermotor Epilepsy.International journal of molecular sciences · 2025Review
- Subcortical Circuits Among Pedunculopontine Nucleus, Thalamus and Basal Ganglia Play Important Roles in Paroxysmal Arousal in Genetic Rat Models of Autosomal Dominant Sleep-Related Hypermotor Epilepsy.International journal of molecular sciences · 2025Article
- Review
- Dysfunction of the NMDA Receptor in the Pathophysiology of Schizophrenia and/or the Pathomechanisms of Treatment-Resistant Schizophrenia.Biomolecules · 2024Review
- Fluorocitrate inhibition of astrocytes reduces nicotine self-administration and alters extracellular levels of glutamate and dopamine within the nucleus accumbens in male wistar rats.Neuropharmacology · 2024Article
- Age-Dependent Activation of Pannexin1 Function Contributes to the Development of Epileptogenesis in Autosomal Dominant Sleep-related Hypermotor Epilepsy Model Rats.International journal of molecular sciences · 2024Article
- Astrocytic Regulation of Endocannabinoid-Dependent Synaptic Plasticity in the Dorsolateral Striatum.International journal of molecular sciences · 2024Article
- Enhanced L-β-Aminoisobutyric Acid Is Involved in the Pathophysiology of Effectiveness for Treatment-Resistant Schizophrenia and Adverse Reactions of Clozapine.Biomolecules · 2023Article
- A Candidate Gliotransmitter, L-β-Aminoisobutyrate, Contributes to Weight Gain and Metabolic Complication Induced by Atypical Antipsychotics.Nutrients · 2023Article
- Astrocytes as a target for therapeutic strategies in epilepsy: current insights.Frontiers in molecular neuroscience · 2023Review
- Dose-Dependent Biphasic Action of Quetiapine on AMPK Signalling via 5-HT7 Receptor: Exploring Pathophysiology of Clinical and Adverse Effects of Quetiapine.International journal of molecular sciences · 2022Article
- Brexpiprazole Reduces 5-HT7 Receptor Function on Astroglial Transmission Systems.International journal of molecular sciences · 2022Article
- Can rodent models elucidate the pathomechanisms of genetic epilepsy?British journal of pharmacology · 2022Review
- The role of S100B/RAGE-enhanced ADAM17 activation in endothelial glycocalyx shedding after traumatic brain injury.Journal of neuroinflammation · 2022Article
- The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats.Annals of neurosciences · 2022Article
- Electrochemical Determination of Kynurenine Pathway Metabolites-Challenges and Perspectives.Sensors (Basel, Switzerland) · 2021Review
- Distinct Effects of Escitalopram and Vortioxetine on Astroglial L-Glutamate Release Associated with Connexin43.International journal of molecular sciences · 2021Article
- Comparing astrocytic gap junction of genetic absence epileptic rats with control rats: an experimental study.Brain structure & function · 2021Article
- Effects of Atypical Antipsychotics, Clozapine, Quetiapine and Brexpiprazole on Astroglial Transmission Associated with Connexin43.International journal of molecular sciences · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAnticonvulsants have been developed according to the traditional neurotransmission imbalance hypothesis. However, the anticonvulsive pharmacotherapy currently available remains unsatisfactory. To develop new antiepileptic drugs with novel antiepileptic mechanisms, we have tested the antiepileptic actions of ONO-2506, a glial modulating agent, and its effects on tripartite synaptic transmission. EXPERIMENTAL APPROACH: Dose-dependent effects of ONO-2506 on maximal-electroshock seizure (MES), pentylenetetrazol-induced seizure (PTZ) and epileptic discharge were determined in a genetic model of absence epilepsy in mice (Cacna1a(tm2Nobs/tm2Nobs) strain). Antiepileptic mechanisms of ONO-2506 were analysed by examining the interaction between ONO-2506 and transmission-modulating toxins (tetanus toxin, fluorocitrate, tetrodotoxin) on release of l-glutamate, d-serine, GABA and kynurenic acid in the medial-prefrontal cortex (mPFC) of freely moving rats using microdialysis and primary cultured rat astrocytes. KEY
resultsONO-2506 inhibited spontaneous epileptic discharges in Cacna1a(tm2Nobs/tm2Nobs) mice without affecting MES or PTZ. Given systemically, ONO-2506 increased basal release of GABA and kynurenic acid in the mPFC through activation of both neuronal and glial exocytosis, but inhibited depolarization-induced releases of all transmitters. ONO-2506 increased basal glial release of kynurenic acid without affecting those of l-glutamate, d-serine or GABA. However, ONO-2506 inhibited AMPA-induced releases of l-glutamate, d-serine, GABA and kynurenic acid. CONCLUSIONS AND IMPLICATIONS: ONO-2506 did not affect traditional convulsive tests but markedly inhibited epileptic phenomena in the genetic epilepsy mouse model. ONO-2506 enhanced release of inhibitory neuro- and gliotransmitters during the resting stage and inhibited tripartite transmission during the hyperactive stage. The results suggest that ONO-2506 is a novel potential glial-targeting antiepileptic drug. LINKED ARTICLE: This article is commented on by Onat, pp. 1086-1087 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12050.
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