Physostigmine and Adjunct Pretreatment (Alone and Together with Therapy) against Nerve Agent Intoxication

摘要

An ideal pretreatment for soman intoxication should not cause a behavioral decrement when given alone and should prevent soman-induced lethality and convulsions (CNV) and rapidly reverse physical incapacitation. Adjunct (ADJ) doses for each behavioral-deficit-free (BDF) pretreatment regimen for guinea pigs were determined using a one-way shuttle avoidance test. Effective adjuncts (mg/kg. im) tested were aprophen, atropine (AT), azaprophen (AZA), benactyzine, benztropine (BT), dextromethorphan, ethopropazine, promethazine, scopolamine, and trihexyphenidyl. Physostigmine alone reduced the occurrence of CNV and lethality by 42 and 60%, respectively; in combination with each adjunct, lethality was reduced to 0, and recovery from signs of intoxication was < 2 hrs. Also, CNVs were significantly reduced, compared to Phy alone, in animals protected with PRGs containing AT, AZA or SC. A PRG that contained AZA, AT or BT afforded complete protection against lethality induced by 5 LD50s of soman. In general, the PRGS were more effective against lethal and nonlethal intoxication caused by VX, sarin and tabun. These findings show that several BDF PRGs are effective against nerve agent intoxication in guinea pigs. (AW)