Efficacy of the Tertiary Oxime Monoisonitrosoacetone (MINA) Against Lethal Sarin Intoxication in the Guinea Pig

Abstract

A major limitation of currently available oximes is their inability to readily cross the blood brain barrier and reactivate acetylcholinesterase (AChE) that has been inhibited by nerve agents. MINA is a tertiary oxime that readily enters the brain and was reported more than 50 years ago to be effective against lethal nerve agent intoxication. The purpose of this preliminary study was to re-evaluate the efficacy of MINA as a treatment for lethal sarin (GB) intoxication in guinea pigs. Male animals were challenged subcutaneously (s.c.) with 2 LD50s of GB and treated 1 min later with MINA, 2PAM, atropine, or diazepam alone or in various combinations. A total of 14 different treatment groups were evaluated, 7 with MINA and 7 without MINA. Survival was assessed 24 hr after GB challenge. All 69 (100%) animals treated with MINA survived, whereas only 26 of 70 (37%) animals without MINA survived. The results clearly demonstrate the effectiveness of MINA and the potential benefit of using oximes that are readily able to enter the brain.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2007
Accession Number
ADA502025

Entities

People

  • Irwin Koplovitz
  • Susan M. Schulz

Organizations

  • United States Army Medical Research Institute of Chemical Defense

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Alcohols
  • Animals
  • Anticonvulsants
  • Atropine
  • Biomedical Research
  • Blood-Brain Barrier
  • Brain
  • Chemical Compounds
  • Department Of Defense
  • Enzyme Inhibitors
  • Intoxication
  • Laboratory Animals
  • Nerve Agents
  • Rodents
  • Survival
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Neurotoxicology