Atropine and oxime treatment in lethal soman poisoning of anaesthetized guinea-pigs: HLö 7 dimethanesulfonate versus HI 6 dichloride

Pharmacol Toxicol. 1993 Jan;72(1):13-21. doi: 10.1111/j.1600-0773.1993.tb01332.x.

Abstract

The oxime HI 6 is considered to be effective in soman poisoning and less effective in tabun poisoning. Recently, HLö 7 was shown to reactivate acetylcholinesterase (AChE) inhibited by soman and tabun. Therefore, the efficacy of HLö 7 and HI 6 was compared in soman poisoned guinea-pigs. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the a. carotis, v. jugularis and trachea were cannulated. After base line measurements soman 0.08 mg/kg (= 5 x LD50) or 0.16 mg/kg (= 10 x LD50) was injected intravenously, 2 min. later the antidotes were applied intravenously: HLö 7 0.03 or 0.1 mmol/kg, HI 6 0.03 or 0.1 mmol/kg, atropine 10 mg/kg, or a combination of atropine and an oxime. Respiratory and circulatory parameters were recorded for 60 min. or until the death of the animal. The injection of 5 x LD50 soman resulted in a rapid respiratory arrest followed by circulatory failure in the soman and soman plus oxime groups (survival time about 7 min). Atropine restored the circulatory parameters to base line but was unable to provide a sufficient respiratory function (survival time 26 min.). The combination therapy with atropine plus HLö 7 or HI 6 improved the respiration sufficiently, restored the circulation completely, and prolonged the survival time to about 50 min. Atropine treatment was insufficient in animals poisoned with 10 x LD50 soman. The combination of atropine and HLö 7 or HI 6 improved respiration, circulation, and survival time to various extent. Despite of the striking therapeutic effect no reactivation of erythrocyte AChE by the antidotes was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholinesterase / metabolism
  • Anesthesia
  • Animals
  • Antidotes / therapeutic use*
  • Atropine / therapeutic use*
  • Cholinesterase Reactivators / therapeutic use*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Erythrocytes / drug effects
  • Female
  • Guinea Pigs
  • Hemodynamics / drug effects
  • Oximes
  • Poisoning / drug therapy
  • Pyridines / therapeutic use*
  • Pyridinium Compounds / therapeutic use*
  • Respiration / drug effects
  • Soman / poisoning*

Substances

  • Antidotes
  • Cholinesterase Reactivators
  • Oximes
  • Pyridines
  • Pyridinium Compounds
  • HLo 7
  • Atropine
  • Soman
  • Acetylcholinesterase
  • asoxime chloride