Non-Cholinesterase Effects of Anticholinesterases

Abstract

Largely through an interest in developing agricultural pesticides, the I.G. Farbenindustrie in the mid-1930’s began a synthetic program under the direction of Gerhard Schrader. Organophosphorus compounds had previously been described with insecticidal properties by Lange but had attracted little attention prior to that time. In the course of synthesis, Schrader became aware of a miosis and other mild symptoms which were ascribable to the action of the organophosphates. His synthetic studies lead to the formation of diisopropylfluorophosphate (DFP) and some 2,000 other compounds of which about 10% were toxic. From animal studies, it was early recognized that their pharmacologic action resembled that of eserine (physostigmine) except that inhibition of Cholinesterase was irreversible. Largely through an interest in developing more potent chemical warfare agents on the lines of Schrader, the potent organophosphates Tabun (ethyl N, N-di-methylphosphoramidocyanidate) Sarin (isopropyl-methylphosphonofluoridate) and Soman (pinacolyl-methylphosphonofluoridate) were synthesized in large quantity and their potent toxic action studied. A thorough coverage of this topic may be found in an informative discussion by Professor Bo Holmstedt (1963).