Efficacy of atropine/pralidoxime/diazepam or atropine/HI-6/prodiazepam in primates intoxicated by soman.
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.
Lallement
G
G
Unité de Neurotoxicologie, Centre de Recherches du Service de Santé des Armées, La Tronche, France.
Clarencon
D
D
Brochier
G
G
Baubichon
D
D
Galonnier
M
M
Blanchet
G
G
Mestries
J C
JC
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D003975:Diazepam / Q000627:therapeutic use; D004151:Dipeptides / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D010091:Oximes; D011041:Poisoning / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011220:Pralidoxime Compounds / Q000627:therapeutic use; D011355:Prodrugs / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000627:therapeutic use; D012999:Soman / Q000506:poisoning*
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D004151:Dipeptides; D010091:Oximes; D011220:Pralidoxime Compounds; D011355:Prodrugs; D011726:Pyridinium Compounds; C065249:pro-diazepam; D001285:Atropine; D012999:Soman; C022870:asoxime chloride; C028797:pralidoxime; D003975:Diazepam