Efficacy of Atropine/Pralidoxime/Diazepam or Atropine/HI-6/Prodiazepam in Primates Intoxicated by Soman

• Published in: Pharmacology, biochemistry and behavior Vol. 56; no. 2; pp. 325 - 332
• Main Authors: Lallement, Guy, Clarencon, Didier, Brochier, Guy, Baubichon, Dominique, Galonnier, Monique, Blanchet, Guy, Mestries, Jean-Claude
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.02.1997; Elsevier Science
• Subjects: Animals; Antidotes - therapeutic use; Atropine; Atropine - therapeutic use; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; Cholinesterase Inhibitors - poisoning; Diazepam; Diazepam - therapeutic use; Dipeptides - therapeutic use; Drug Therapy, Combination; Electrocardiography - drug effects; Electroencephalography - drug effects; Epilepsy; Macaca fascicularis; Male; Medical sciences; Oximes; Poisoning - drug therapy; Poisoning - pathology; Poisoning - physiopathology; Pralidoxime Compounds - therapeutic use; Primates; Prodrugs - therapeutic use; Pyridinium Compounds - therapeutic use; Soman; Soman - poisoning; Toxicology; Various organic compounds; Oximes; Atropine; Primates; Soman; Epilepsy; Diazepam; Drug combination; Nervous system diseases; Toxicity; Treatment efficiency; Monkey; Oxime; Anticonvulsant; Prodrug; Intramuscular administration; Chemical warfare agent; Vertebrata; Chemotherapy; Mammalia; Animal; Benzodiazepine derivatives; Drug interaction; Poisoning; Organophosphorus compounds; Anticholinesterase agent; Parasympatholytic
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(96)00292-4

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/pralidoxime/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.