PROTECTION OF CHOLINESTERASE AGAINST IRREVERSIBLE INACTIVATION BY DI-ISOPROPYL FLUOROPHOSPHATE IN VITRO

¹ Pharmacology Section, Medical Division, Edgewood Arsenal, Maryland

1. Eserine, by combining reversibly with rat brain cholinesterase, has been shown to protect the enzyme against irreversible inactivation by DFP in vitro. The degree of protection varied directly with the concentration of eserine used. It is concluded that this phenomenon might explain the mechanism by which prophylactic eserine protects cats against DFP poisoning in vivo.

2. Of nineteen other anticholinesterase drugs similarly tested, two showed marked protection (prostigmin and carbamylcholine), six afforded relatively slight protection (pilocarpine, nicotine, atropine, choline, procaine and morphine) and eleven showed none (methylene blue, strychnine, atabrine, quinine, sodium fluoride, thiamin, cysteine, sodium p-amino-benzoate, acetyl-beta-methylcholine, acetyicholine and Intocostrin). The protective property does not appear to depend on the potency of anticholinesterase activity alone, but also on the ability of a compound to compete with DFP for a specific active group of the cholinesterase molecule.