ArticleEnvironmental health perspectives2011
RDX binds to the GABA(A) receptor-convulsant site and blocks GABA(A) receptor-mediated currents in the amygdala: a mechanism for RDX-induced seizures.
Article in Environmental health perspectives, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Conserved toxic responses across divergent phylogenetic lineages: a meta-analysis of the neurotoxic effects of RDX among multiple species using toxicogenomics.Ecotoxicology (London, England) · 2011Pooled it
- Review
- A Mind-Blowing Ingestion: Intentional Plastic Explosive Consumption Resulting in Seizures.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2025Article
- Toxic Effects of the Most Common Components of Energetic Co-Crystals.Molecules (Basel, Switzerland) · 2025Review
- Article
- Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) causes seizure activity in larval zebrafish via antagonism of γ-aminobutyric acid type A receptor α1β2γ2.Archives of toxicology · 2023Article
- The seizure-inducing plastic explosive RDX inhibits the α1β2γ2 GABAAnnals of clinical and translational neurology · 2022Article
- Building a Network of Adverse Outcome Pathways (AOPs) Incorporating the Tau-Driven AOP Toward Memory Loss (AOP429).Journal of Alzheimer's disease reports · 2022Review
- Peer Pressure = Explosive Consequences: A Case Report of Toxic Ingestion of Cyclonite (C-4) Explosive on a Dare.Clinical practice and cases in emergency medicine · 2021Article
- Review
- ASIC1a activation enhances inhibition in the basolateral amygdala and reduces anxiety.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- MicroRNA and messenger RNA profiling reveals new biomarkers and mechanisms for RDX induced neurotoxicity.BMC genomics · 2014Article
- α7-Containing nicotinic acetylcholine receptors on interneurons of the basolateral amygdala and their role in the regulation of the network excitability.Journal of neurophysiology · 2013Article
- Current perspectives on the use of alternative species in human health and ecological hazard assessments.Environmental health perspectives · 2013Review
- Interspecific effects of 4A-DNT (4-amino-2,6-dinitrotoluene) and RDX (1,3,5-trinitro-1,3,5-triazine) in Japanese quail, Northern bobwhite, and Zebra finch.Ecotoxicology (London, England) · 2013Article
- Biochemical and microbial analysis of ovine rumen fluid incubated with 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX).Current microbiology · 2012Article
- Non-coding RNAs--novel targets in neurotoxicity.Neurotoxicology · 2012Review
- Evaluation of natural and nitramine binding energies to 3-D models of the S1S2 domains in the N-methyl-D-aspartate receptor.Journal of molecular modeling · 2012Article
- Gene expression analysis of CL-20-induced reversible neurotoxicity reveals GABA(A) receptors as potential targets in the earthworm Eisenia fetida.Environmental science & technology · 2012Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) is a high-energy, trinitrated cyclic compound that has been used worldwide since World War II as an explosive in both military and civilian applications. RDX can be released in the environment by way of waste streams generated during the manufacture, use, and disposal of RDX-containing munitions and can leach into groundwater from unexploded munitions found on training ranges. For > 60 years, it has been known that exposure to high doses of RDX causes generalized seizures, but the mechanism has remained unknown.
objectiveWe investigated the mechanism by which RDX induces seizures. METHODS AND
resultsBy screening the affinity of RDX for a number of neurotransmitter receptors, we found that RDX binds exclusively to the picrotoxin convulsant site of the γ-aminobutyric acid type A (GABA(A)) ionophore. Whole-cell in vitro recordings in the rat basolateral amygdala (BLA) showed that RDX reduces the frequency and amplitude of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic currents and the amplitude of GABA-evoked postsynaptic currents. In extracellular field recordings from the BLA, RDX induced prolonged, seizure-like neuronal discharges.
conclusionsThese results suggest that binding to the GABA(A) receptor convulsant site is the primary mechanism of seizure induction by RDX and that reduction of GABAergic inhibitory transmission in the amygdala is involved in the generation of RDX-induced seizures. Knowledge of the molecular site and the mechanism of RDX action with respect to seizure induction can guide therapeutic strategies, allow more accurate development of safe thresholds for exposures, and help prevent the development of new explosives or other munitions that could pose similar health risks.
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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.