ArticlePloS one2016
Critical Evaluation of P2X7 Receptor Antagonists in Selected Seizure Models.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- P2X7R Signaling and Differential Regulation of Neuroinflammatory and Behavior Responses in Male and Female Mice During Chronic Ethanol Exposure.International journal of molecular sciences · 2026Article
- A Bibliometric Analysis of P2X7R in Cardiovascular Diseases from 2005 to 2024.Current cardiology reviews · 2026Review
- The Multifaceted Role of P2X7R in Microglia and Astrocytes.Neurochemical research · 2025Review
- Purinergic receptor antagonism reduces interictal discharges and rescues cognitive function in a mouse model of temporal lobe epilepsy.Frontiers in neuroscience · 2025Article
- P2X7R antagonism suppresses long-lasting brain hyperexcitability following traumatic brain injury in mice.Theranostics · 2025Article
- Neuroinflammatory responses and blood-brain barrier injury in chronic alcohol exposure: role of purinergic P2 × 7 Receptor signaling.Journal of neuroinflammation · 2024Article
- Pharmacological interaction and immune response of purinergic receptors in therapeutic modulation.Purinergic signalling · 2024Review
- The Purinergic P2X7 Receptor as a Target for Adjunctive Treatment for Drug-Refractory Epilepsy.International journal of molecular sciences · 2024Review
- Functional expression of the ATP-gated P2X7 receptor in human iPSC-derived astrocytes.Purinergic signalling · 2024Article
- The P2X7 Receptor as a Mechanistic Biomarker for Epilepsy.International journal of molecular sciences · 2023Review
- Anti-seizure effects of JNJ-54175446 in the intra-amygdala kainic acid model of drug-resistant temporal lobe epilepsy in mice.Frontiers in pharmacology · 2023Article
- Astrocytes in the initiation and progression of epilepsy.Nature reviews. Neurology · 2022Review
- Panx1 channels promote both anti- and pro-seizure-like activities in the zebrafish via p2rx7 receptors and ATP signaling.Communications biology · 2022Article
- Beyond Seizure Control: Treating Comorbidities in Epilepsy via Targeting of the P2X7 Receptor.International journal of molecular sciences · 2022Review
- Mesial Temporal Lobe Epilepsy (MTLE) Drug-Refractoriness Is Associated With P2X7 Receptors Overexpression in the Human Hippocampus and Temporal Neocortex and May Be Predicted by Low Circulating Levels of miR-22.Frontiers in cellular neuroscience · 2022Article
- Analyzing the Role of the P2X7 Receptor in Epilepsy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- ATP and adenosine-Two players in the control of seizures and epilepsy development.Progress in neurobiology · 2021Review
- P2XFrontiers in cellular neuroscience · 2021Review
- Targeting Neuroinflammation via Purinergic P2 Receptors for Disease Modification in Drug-Refractory Epilepsy.Journal of inflammation research · 2021Review
- Characterization of the Expression of the ATP-Gated P2X7 Receptor Following Status Epilepticus and during Epilepsy Using a P2X7-EGFP Reporter Mouse.Neuroscience bulletin · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ATP-gated P2X7 receptor (P2X7R) is a non-selective cation channel which senses high extracellular ATP concentrations and has been suggested as a target for the treatment of neuroinflammation and neurodegenerative diseases. The use of P2X7R antagonists may therefore be a viable approach for treating CNS pathologies, including epileptic disorders. Recent studies showed anticonvulsant potential of P2X7R antagonists in certain animal models. To extend this work, we tested three CNS-permeable P2X7R blocker (Brilliant Blue G, AFC-5128, JNJ-47965567) and a natural compound derivative (tanshinone IIA sulfonate) in four well-characterized animal seizure models. In the maximal electroshock seizure threshold test and the pentylenetetrazol (PTZ) seizure threshold test in mice, none of the four compounds demonstrated anticonvulsant effects when given alone. Notably, in combination with carbamazepine, both AFC-5128 and JNJ-47965567 increased the threshold in the maximal electroshock seizure test. In the PTZ-kindling model in rats, useful for testing antiepileptogenic activities, Brilliant Blue G and tanshinone exhibited a moderate retarding effect, whereas the potent P2X7R blocker AFC-5128 and JNJ-47965567 showed a significant and long-lasting delay in kindling development. In fully kindled rats, the investigated compounds revealed modest effects to reduce the mean seizure stage. Furthermore, AFC-5128- and JNJ-47965567-treated animals displayed strongly reduced Iba 1 and GFAP immunoreactivity in the hippocampal CA3 region. In summary, our results show that P2X7R antagonists possess no remarkable anticonvulsant effects in the used acute screening tests, but can attenuate chemically-induced kindling. Further studies would be of interest to support the concept that P2X7R signalling plays a crucial role in the pathogenesis of epileptic disorders.
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