Evaluation of first-line anticonvulsants to treat nerve agent-induced seizures and prevent neuropathology in adult and pediatric rats

摘要

Risk exists for civilian exposure to nerve agents (NA), and exposure can produce prolonged seizures. Pediatric populations are at greater risk for injury or death due to the central nervous system effects of NAs. To address the need to evaluate the effectiveness of anticonvulsants, pediatric and adult animal models were established to test the effectiveness of anticonvulsant drugs for treating NA-induced seizures in pediatric populations. In this paper, median effective dose (ED50) and neuroprotective effectiveness were determined for the first-line anticonvulsant treatments diazepam and midazolam in pediatric and adult rats against sarin- and VX-induced seizures. Comparisons between treatments were made across postnatal days (PND) 21, 28, and 70 in rats of both sexes. We observed high efficacy and potency of midazolam and diazepam, with low variation in doses across the ages or sexes. These data are important for informing adult and pediatric dosing recommendations for NA-induced seizures.