The positive influence of a cholinergic-anticholinergic pretreatment and antidotal treatment on rats poisoned with supralethal doses of soman.
The influence of pretreatment with the drug mixture (pyridostigmine, benactyzine and trihexyphenidyle), and antidotal treatment (the oxime HI-6 in combination with benactyzine) on respiration, circulation and survival of experimental animals poisoned with supralethal doses of soman (2 x LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. Untreated soman poisoning caused rapid respiratory depression, progressive bradycardia and a short-term increase in the mean arterial pressure, followed immediately by hypotension. The poisoned rats died on average within 10 min from respiratory and circulatory insufficiency. A cholinergic-anticholinergic pretreatment alone partially prevented changes in monitored physiological variables, caused by soman, but only for a few minutes; post-poisoning treatment with antidotes, also alone, had similar effects. The rats died on average within 30 min from respiratory and circulatory failure. When rats were pretreated by the drug mixture and treated by antidotes, respiration as well as circulation were completely restored and the rats survived at least 120 min following soman challenge. The results of the investigation suggest that cholinergic-anticholinergic pretreatment seems able to enhance the efficacy of antidotal treatment in restoring respiratory and circulatory changes induced by soman.
Kassa
J
J
Purkyne Military Medical Academy, Hradec Králové, Czech Republic.
Fusek
J
J
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D018678:Cholinergic Agents / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004338:Drug Combinations; D004562:Electrocardiography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D012999:Soman / Q000633:toxicity*
D000931:Antidotes; D018678:Cholinergic Agents; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D004338:Drug Combinations; D012999:Soman