Accession Number:

ADA621400

Title:

Evaluating the Anti-Seizure Efficacy of Novel Adenosine Treatment Regimens in a Soman Rat Model

Descriptive Note:

Technical rept. May 2013-Mar 2014

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD

Report Date:

2015-06-01

Pagination or Media Count:

26.0

Abstract:

The severe brain-damaging effects of organophosphorus nerve agents are difficult to treat with current medical countermeasures. Diazepam and midazolam have been shown to have anti-seizure capabilities but are limited by sensitivities to dosing and timing parameters. We recently reported that central adenosine receptor AR stimulation with the adenosine A1 agonist 6-cyclopentyladenosine CPA improved survivability and minimized neuropathology after soman intoxication. The goal for this study was to further explore adenosine s therapeutic applications and obtain a deeper understanding of the neuroprotective mechanism. We first investigated the neuroprotective efficacy of intracerebroventricularly delivered CPA 700 g when given 20 minutes after the onset of soman-induced seizure. To further promote survival, we then tested the therapeutic benefit of incorporating monoisonitrosoacetone, a centrally active cholinesterase-reactivating oxime. Since it is important to return the warfighter to combat after treatment, our last objective was to investigate if the centrally acting AR antagonist 8-cyclopentyl-1,3-dipropylxanthine could reverse CPA-induced sedation. Although further study is needed to validate efficacy and safety, the results from this study demonstrated that both peripherally and centrally delivered adenosine agonists have significant therapeutic benefits for acute and delayed treatment of nerve agent poisoning.

Subject Categories:

  • Biochemistry
  • Medicine and Medical Research
  • Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE