ArticleFrontiers in pharmacology2023
Anti-seizure effects of JNJ-54175446 in the intra-amygdala kainic acid model of drug-resistant temporal lobe epilepsy in mice.
Article in Frontiers in pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics.Brain : a journal of neurology · 2026Article
- Article
- Identification of EEG features during status epilepticus for prediction of emergent epilepsy phenotype in the mouse intra-amygdala kainic acid model using supervised learning.IBRO neuroscience reports · 2026Article
- Review
- Attenuated Single Neuron and Network Hyperexcitability Following MicroRNA-134 Inhibition in Mice with Drug-Resistant Temporal Lobe Epilepsy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Microglial pathological synaptic pruning in epilepsy: pathophysiology and therapeutic potential.Frontiers in immunology · 2026Review
- Sleep and circadian rhythm disruptions in animal models of temporal lobe epilepsy.Frontiers in neuroscience · 2026Review
- P2X7R antagonism suppresses long-lasting brain hyperexcitability following traumatic brain injury in mice.Theranostics · 2025Article
- The Purinergic P2X7 Receptor as a Target for Adjunctive Treatment for Drug-Refractory Epilepsy.International journal of molecular sciences · 2024Review
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
There remains a need for new drug targets for treatment-resistant temporal lobe epilepsy. The ATP-gated P2X7 receptor coordinates neuroinflammatory responses to tissue injury. Previous studies in mice reported that the P2X7 receptor antagonist JNJ-47965567 suppressed spontaneous seizures in the intraamygdala kainic acid model of epilepsy and reduced attendant gliosis in the hippocampus. The drug-resistance profile of this model is not fully characterised, however, and newer P2X7 receptor antagonists with superior pharmacokinetic profiles have recently entered clinical trials. Using telemetry-based continuous EEG recordings in mice, we demonstrate that spontaneous recurrent seizures in the intraamygdala kainic acid model are refractory to the common anti-seizure medicine levetiracetam. In contrast, once-daily dosing of JNJ-54175446 (30 mg/kg, intraperitoneal) resulted in a significant reduction in spontaneous recurrent seizures which lasted several days after the end of drug administration. Using a combination of immunohistochemistry and
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