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, b enactyzine and trihexyphenidyle), and antidotal treatment (the oxime H I-6 in combination with benactyzine) on respiration, circulation and s urvival of experimental animals poisoned with supralethal doses of som an (2 x LD50) was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. Untreated soman poisoning c aused rapid respiratory depression, progressive bradycardia and a shor t-term increase in the mean arterial pressure, followed immediately by hypotension. The poisoned rats died on average within 10 min from res piratory and circulatory insufficiency. A cholinergic-anticholinergic pretreatment alone partially prevented changes in monitored physiologi cal variables, caused by soman, but only for a few minutes; post-poiso ning treatment with antidotes, also alone, had similar effects. The ra ts died on average within 30 min from respiratory and circulatory fail ure. When rats were pretreated by the drug mixture and treated by anti dotes, respiration as well as circulation were completely restored and the rats survived at least 120 min following soman challenge. The res ults of the investigation suggest that cholinergic-anticholinergic pre treatment seems able to enhance the efficacy of antidotal treatment in restoring respiratory and circulatory changes induced by soman. (C) 1 998 Elsevier Science Ireland Ltd. All rights reserved.