Efficacy of atropine/pralidoxime/diazepam or atropine/HI-6/prodiazepam in primates intoxicated by soman

Pharmacol Biochem Behav. 1997 Feb;56(2):325-32. doi: 10.1016/s0091-3057(96)00292-4.

Abstract

We performed an experiment to characterize the toxicity of soman in cynomolgus monkeys when the organophosphorus intoxication was followed by a treatment with either the three-drug therapy atropine/pralidoxime/diazepam or the association atropine/HI-6/prodiazepam. Clinical, electrophysiological and histological approaches were combined. Our data demonstrate that the protection afforded against soman toxicity was better with the combination atropine/HI-6/prodiazepam compared to atropine/pralidoxime/diazepam. This was observed transiently in term of vigilance and respiratory function of intoxicated animals, but particularly in term of their EEG- and ECG disturbances. Moreover, compared to those treated with atropine/pralidoxine/diazepam, animals treated with atropine/ HI-6/prodiazepam recovered slightly sooner and did not exhibit prostration 2 days after intoxication although their rapidity of movements was not totally restored. The final recovery observed 3 weeks after intoxication was similar for the two groups. The value of the combination of atropine/HI-6/prodiazepam vs atropine/pralidoxime/diazepam to counteract soman toxicity was also confirmed in term of brain neuroprotection since greater lesions were observed with the second three drug treatment three weeks after intoxication.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidotes / therapeutic use*
  • Atropine / therapeutic use
  • Cholinesterase Inhibitors / poisoning*
  • Diazepam / therapeutic use
  • Dipeptides / therapeutic use
  • Drug Therapy, Combination
  • Electrocardiography / drug effects
  • Electroencephalography / drug effects
  • Macaca fascicularis
  • Male
  • Oximes
  • Poisoning / drug therapy
  • Poisoning / pathology
  • Poisoning / physiopathology
  • Pralidoxime Compounds / therapeutic use
  • Prodrugs / therapeutic use
  • Pyridinium Compounds / therapeutic use
  • Soman / poisoning*

Substances

  • Antidotes
  • Cholinesterase Inhibitors
  • Dipeptides
  • Oximes
  • Pralidoxime Compounds
  • Prodrugs
  • Pyridinium Compounds
  • pro-diazepam
  • Atropine
  • Soman
  • asoxime chloride
  • pralidoxime
  • Diazepam