ArticleNeuropharmacology2015
Combined treatment with diazepam and allopregnanolone reverses tetramethylenedisulfotetramine (TETS)-induced calcium dysregulation in cultured neurons and protects TETS-intoxicated mice against lethal seizures.
Article in Neuropharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Low-Frequency rTMS and Diazepam Exert Synergistic Effects on the Excitability of an SH-SY5Y Model of Epileptiform Activity.Biomedicines · 2025Article
- Evaluation of Midazolam-Ketamine-Allopregnanolone Combination Therapy against Cholinergic-Induced Status Epilepticus in Rats.The Journal of pharmacology and experimental therapeutics · 2024Article
- Tolerability and pharmacokinetics of intravenous allopregnanolone with and without midazolam pretreatment in two healthy dogs.Epilepsia open · 2023Article
- Novel neurosteroid pregnanolone pyroglutamate suppresses neurotoxicity syndrome induced by tetramethylenedisulfotetramine but is ineffective in a rodent model of infantile spasms.Pharmacological reports : PR · 2023Article
- Perampanel, a potent AMPA receptor antagonist, protects against tetramethylenedisulfotetramine-induced seizures and lethality in mice: comparison with diazepam.Archives of toxicology · 2021Article
- Structure-Activity Relationship of Neuroactive Steroids, Midazolam, and Perampanel Toward Mitigating Tetramine-Triggered Activity in Murine Hippocampal Neuronal Networks.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Allopregnanolone and perampanel as adjuncts to midazolam for treating diisopropylfluorophosphate-induced status epilepticus in rats.Annals of the New York Academy of Sciences · 2020Article
- Tetramethylenedisulfotetramine neurotoxicity: What have we learned in the past 70 years?Neurobiology of disease · 2020Review
- Neurosteroid and benzodiazepine combination therapy reduces status epilepticus and long-term effects of whole-body sarin exposure in rats.Epilepsia open · 2019Article
- Tetramethylenedisulfotetramine: A Health Risk Compound and a Potential Chemical Warfare Agent.Toxics · 2018Review
- Developmental and sex differences in tetramethylenedisulfotetramine (TMDT)-induced syndrome in rats.Developmental neurobiology · 2018Article
- Behavioral intoxication following voluntary oral ingestion of tetramethylenedisulfotetramine: Dose-dependent onset, severity, survival, and recovery.Neurotoxicology · 2017Article
- First-in-man allopregnanolone use in super-refractory status epilepticus.Annals of clinical and translational neurology · 2017Article
- Influence of tetramethylenedisulfotetramine on synchronous calcium oscillations at distinct developmental stages of hippocampal neuronal cultures.Neurotoxicology · 2017Article
- Models to identify treatments for the acute and persistent effects of seizure-inducing chemical threat agents.Annals of the New York Academy of Sciences · 2016Review
- Tetramethylenedisulfotetramine: pest control gone awry.Annals of the New York Academy of Sciences · 2016Review
- 5α-reduced progestogens ameliorate mood-related behavioral pathology, neurotoxicity, and microgliosis associated with exposure to HIV-1 Tat.Brain, behavior, and immunity · 2016Article
- Repurposing psychiatric medicines to target activated microglia in anxious mild cognitive impairment and early Parkinson's disease.American journal of neurodegenerative disease · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Tetramethylenedisulfotetramine (TETS) is a potent convulsant GABAA receptor blocker. Mice receiving a lethal dose of TETS (0.15 mg/kg i.p.) are rescued from death by a high dose of diazepam (5 mg/kg i.p.) administered shortly after the second clonic seizure (∼20 min post-TETS). However, this high dose of diazepam significantly impairs blood pressure and mobility, and does not prevent TETS-induced neuroinflammation in the brain. We previously demonstrated that TETS alters synchronous Ca(2+) oscillations in primary mouse hippocampal neuronal cell cultures and that pretreatment with the combination of diazepam and allopregnanolone at concentrations having negligible effects individually prevents TETS effects on intracellular Ca(2+) dynamics. Here, we show that treatment with diazepam and allopregnanolone (0.1 μM) 20 min after TETS challenge normalizes synchronous Ca(2+) oscillations when added in combination but not when added singly. Similarly, doses (0.03-0.1 mg/kg i.p.) of diazepam and allopregnanolone that provide minimal protection when administered singly to TETS intoxicated mice increase survival from 10% to 90% when given in combination either 10 min prior to TETS or following the second clonic seizure. This therapeutic combination has negligible effects on blood pressure or mobility. Combined treatment with diazepam and allopregnanolone also decreases TETS-induced microglial activation. Diazepam and allopregnanolone have distinct actions as positive allosteric modulators of GABAA receptors that in combination enhance survival and mitigate neuropathology following TETS intoxication without the adverse side effects associated with high dose benzodiazepines. Combination therapy with a benzodiazepine and neurosteroid represents a novel neurotherapeutic strategy with potentially broad application.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.