REACTIVATION OF DFP-INACTIVATED ACETYLCHOLINESTERASE BY MONOISONITROSOACETONE (MINA) AND DIACETYLMONOXIME (DAM) IN VIVO

¹ Department of Physiology and Pharmacology, Graduate School of Medicine, University of Pennsylvania, Philadelphia 4

A comparison was made of the abilities of monoisonitrosoacetone (MINA) and diacetylmonoxime (DAM) to reactivate disopropyl-fluorophosphate (DFP)-inactivated acetylcholinesterase (AChE) of the autonomic ganglia and motor endplates of cats, using both the Warburg and histochemical techniques. By the former method, AChE-reactivation was demonstrated only in ganglionic tissue when the higher dose (0.4 mM/kgm., i.v.) of MINA was given 20 minutes after DFP (0.02 mM/kgm., i.v.). Reactivation was detected histochemically in ganglia and at the motor endplate after the higher or lower (0.04 mM/kgm., i.v.) dose of either agent at the same time interval. Considerably greater reactivation was noted after the higher dose with either agent; at equivalent doses, MINA produced more reactivation than did DAM. When the lower dose of either agent was given one hour after DFP, reactivation was noted at ganglionic sites only after MINA.

Results are discussed in relation to mechanisms other than AChE-reactivation which may contribute to the protection afforded by the nucleophilic agents against alkylphosphate anti-ChE poisoning.