Survey of drug therapies against acute oral tetramethylenedisulfotetramine poisoning in a rat voluntary consumption model.

Survey of drug therapies against acute oral tetramethylenedisulfotetramine poisoning in a rat voluntary consumption model. Neurotoxicology. 2019 Aug 10;: Authors: Moffett MC, Rauscher NA, Rice NC, Myers TM Abstract Ingestion of the noncompetitive GABAA receptor antagonist tetramethylenedisulfotetramine (TETS) results in arrhythmias, respiratory depression, and life-threatening convulsive status epilepticus. We have previously developed a realistic model of voluntary TETS consumption, in which rats promptly consumed a piece of cereal containing a dose of TETS that led to rapid progression of toxic signs (including convulsions) and profound and enduring behavioral suppression. Recently, this model was used to survey nine different drugs from distinct drug classes over a large range of doses to identify possible therapeutics. The drugs included three benzodiazepines (diazepam, midazolam, and lorazepam), two barbiturates (phenobarbital and pentobarbital), the GABAA allosteric modulator allopregnanolone, and three non-traditional therapeutics (dexmedetomidine, ketamine, and ethanol). Treatment was administered intraperitoneally 10 minutes after consumption of the cereal morsel containing TETS (600 µg/kg). This exposure model resulted in a survival rate of 30% in vehicle-treated rats. Diazepam (12.5 mg/kg) and midazolam (25 mg/kg), compared to vehicle, significantly increased survival (75 and 100% respectively) but at only one of ...
Source: Neurotoxicology - Category: Neurology Authors: Tags: Neurotoxicology Source Type: research