Accession Number:

ADA555367

Title:

Evaluation of ADD392124 for the Delayed Treatment of Nerve Agent-Induced Status Epilepticus Seizures

Descriptive Note:

Technical rept. 15 Nov 2009-30 Jan 2010

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2011-09-01

Pagination or Media Count:

16.0

Abstract:

ADD392124 was identified by the Anticonvulsant Screening Program as being able to control benzodiazepine-resistant status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a convulsant dose of soman. Seizures were allowed to develop, and the standard treatment for nerve agent intoxication--atropine, 2-PAM an oxime cholinesterase reactivator, and diazepam a benzodiazepine--was administered at either 5 or 20 min after seizures started along with ADD392124 at varying doses. ADD392124 was capable of stopping soman-induced seizures at both treatment delay times anticonvulsant ED50 at the 5-min treatment delay 256.1 mgkg 226.3 336.9 mgkg, 95 confidence limits anticonvulsant ED50 for the 20-min treatment delay was 325.7 mgkg 291.3 937.5 mgkg, 95 confidence limits. The time for seizure termination following administration of ADD392124 at the 5-min treatment delay time was 533.9 sec 8.9 min, while the latency for seizure termination at the 20-min delay was 2258.3 sec 37.6 min. ADD392124 was less potent as an anticonvulsant when compared to anticholinergics, N-methyl-d-aspartate NMDA antagonists or benzodiazepines. Nevertheless, ADD392124 was successful in terminating soman-induced seizures at delay times e.g., 20 min where few other classes of anticonvulsant drugs have proven effective.

Subject Categories:

  • Pharmacology
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE