Efficacy of antidotes against soman poisoning in female physostigmine-protected rats

Female rats have been found much more sensitive to lethal effects of soman than male rats. Therefore it was of interest to examine the efficacy of different antidotes against soman poisoning in females which are usually not being used in soman poisoning studies. The effects of acetylcholinesterase (AChE) non-reactivating antidotes atropine and diazepam were analyzed in combination with physostigmine prophylaxis against supralethal doses of soman. Physostigmine prophylaxis was much more effective when supplemented by atropine and diazepam therapy, applied at the onset of the first signs of poisoning. The interval between the injection of a supralethal dose of soman and the appearance of signs of poisoning was shorter in physostigmine pretreated animals than in non-pretreated controls poisoned with the same supralethal dose of soman. The prophylactic effect of physostigmine (used at maximal dose) disappeared in about 120 min. The addition of HI-6, an AChE-reactivating oxime, to atropine + diazepam therapy further increased the survival in soman-poisoned and physostigmine-pretreated rats, yielding the highest protective ratio of 6.4. Pretreatment with physostigmine offered marked protection against inhibition of AChE by soman, as shown by enzyme activity determination in different brain regions and in diaphragm muscle. Application of HI-6 in addition to the combination of the above mentioned antidotes even preserved more AChE activity in the skeletal muscle but did not influence inhibition of the enzyme in brain.