EFFECTS OF ATROPINE-OXIME THERAPY ON CHOLINESTERASE ACTIVITY AND SURVIVAL OF ANIMALS INTOXICATED WITH PARA-NITROPHENYL DI-NORMAL-BUTYLPHOSPHINATE

p-Nitrophenyl di-n-butylphosphinate (DBP) is a strong inhibitor of cholinesterase in vitro and in vivo. The half-times for regeneration of DBP-inhibited brain and blood enzyme activity were found to be 103.2 and 47.2 hr, respectively. These values are similar to those found for mice given soman, an irreversible inhibitor of cholinesterase. The absence of spontaneous reactivation of enzyme activity in vivo is supported by in vitro studies on DBP-inhibited eel acetylcholinesterase; no increase in enzyme activity was observed in 48 hr. After maximum inhibition with DBP, male rats were treated im with 44 μmol/kg of TMB-4, 2-PAM, or HS-6. TMB-4 treatment, but not 2-PAM or HS-6, resulted in significant reactivation of inhibited blood enzyme activity. 2-PAM was also markedly less effective than TMB-4 in restoring DBP-inhibited eel enzyme activity. Treatment with atropine alone and with 44 μmol/kg TMB-4, 2-PAM, or HS-6 im at 20 min after poisoning with 2.5 × LD50 DBP resulted in complete protection with TMB-4, 20% protection with 2-PAM or HS-6, and no protection with atropine alone. The data indicate that the response to therapy of animals receiving DBP depends upon the particular oxime used for treatment in conjuction with atropine; 2-PAM may not be the oxime of choice in the treatment of DBP intoxication. © 1979.