ArticleCurrent opinion in toxicology2019
Mechanism-based novel antidotes for organophosphate neurotoxicity.
Article in Current opinion in toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Neurosteroid mitigation of developmental neurological dysfunction, long-term epileptic biomarkers, chronic neuroinflammation, and neurodegeneration in a pediatric rat model of organophosphate exposure.The Journal of pharmacology and experimental therapeutics · 2025Article
- Cystamine reduces neurodegeneration and epileptogenesis following soman-induced status epilepticus in rats.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Quantitative TNeuropharmacology · 2024Article
- A Pediatric Rat Model of Organophosphate-Induced Refractory Status Epilepticus: Characterization of Long-Term Epileptic Seizure Activity, Neurologic Dysfunction and Neurodegeneration.The Journal of pharmacology and experimental therapeutics · 2024Article
- Protective Activity of Novel Hydrophilic Synthetic Neurosteroids on Organophosphate Status Epilepticus-induced Chronic Epileptic Seizures, Non-Convulsive Discharges, High-Frequency Oscillations, and Electrographic Ictal Biomarkers.The Journal of pharmacology and experimental therapeutics · 2024Article
- Neurosteroids as Novel Anticonvulsants for Refractory Status Epilepticus and Medical Countermeasures for Nerve Agents: A 15-Year Journey to Bring Ganaxolone from Bench to Clinic.The Journal of pharmacology and experimental therapeutics · 2024Review
- Progress and Challenges in Developing Medical Countermeasures for Chemical, Biological, Radiological, and Nuclear Threat Agents.The Journal of pharmacology and experimental therapeutics · 2024Article
- Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.The Journal of pharmacology and experimental therapeutics · 2024Article
- Long-Term Neuropsychiatric Developmental Defects after Neonatal Organophosphate Exposure: Mitigation by Synthetic Neurosteroids.The Journal of pharmacology and experimental therapeutics · 2024Article
- Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy.Psychopharmacology · 2023Review
- Pathophysiological basis and promise of experimental therapies for Gulf War Illness, a chronic neuropsychiatric syndrome in veterans.Psychopharmacology · 2023Review
- GABAkines - Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAPharmacology & therapeutics · 2022Review
- Genome-Wide Selective Signature Analysis Revealed Insecticide Resistance Mechanisms inInsects · 2021Article
- Comparative profile of refractory status epilepticus models following exposure of cholinergic agents pilocarpine, DFP, and soman.Neuropharmacology · 2021Article
- Mechanisms of organophosphate neurotoxicity.Current opinion in toxicology · 2021Article
- Novel Genetically Modified Mouse Model to Assess Soman-Induced Toxicity and Medical Countermeasure Efficacy: Human Acetylcholinesterase Knock-in Serum Carboxylesterase Knockout Mice.International journal of molecular sciences · 2021Article
- Magnetic resonance imaging analysis of long-term neuropathology after exposure to the nerve agent soman: correlation with histopathology and neurological dysfunction.Annals of the New York Academy of Sciences · 2020Article
- Phenobarbital as alternate anticonvulsant for organophosphate-induced benzodiazepine-refractory status epilepticus and neuronal injury.Epilepsia open · 2020Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
This article describes current pursuits for developing novel antidotes for organophosphate (OP) intoxication. Recent mechanistic studies of benzodiazepine-resistant seizures have key consequences for victims of OP pesticide and nerve agent attacks. We uncovered why current therapies are not able to stop the OP-induced seizures and brain cell death and what type of drug might be better. OP exposure down regulates critical inhibitory GABA-A receptors, kills neurons, and causes massive neuroinflammation that will cause more neuronal death, which causes the problem of too few benzodiazepine receptors. The loss of inhibitory interneurons creates a self-sustaining seizure circuit and refractory status epilepticus. Thus, there is an urgent need for mechanism-based, new antidotes for OP intoxication. We have discovered neurosteroids as next-generation anticonvulsants superior to midazolam for the treatment of OP poisoning. Neurosteroids that activate both extrasynaptic and synaptic GABA-A receptors have the potential to stop seizures more effectively and safely than benzodiazepines. In addition, neurosteroids confers robust neuroprotection by reducing neuronal injury and neuroinflammation. The synthetic neurosteroid ganaxolone is being considered for advanced development as a future anticonvulsant for nerve agents. Experimental studies shows striking efficacy of ganaxolone and its analogs in OP exposure models. They are also effective in attenuating long-term neuropsychiatric deficits caused by OP exposure. Overall, neurosteroids represent rational anticonvulsants for OP intoxication, even when given late after exposure.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.