EFFECTS IN MAN OF THE ANTICHOLINESTERASE COMPOUND SARIN (ISOPROPYL METHYL PHOSPHONOFLUORIDATE)1

Abstract

In normal subjects, sarin (isopropyl methyl phosphonofluoridate) produced muscarine-like, nicotine-like, and central nervous system signs and symptoms attributable to the in- hibition of cholinesterase enzymes in the effector tissues, and resembling those produced by other organic phosphate anticholinesterase compounds. Of the compounds studied, sarin had the greatest anticholinesterase activity in vitro; it was the most toxic to animals; and it produced its pharmacologic effects in man in the smallest doses. Tetraethyl pyrophosphate, di-isopropyl fluorophosphate and parathion were less potent, in that order. The amount of enzyme inhibited by a given dose was proportional to the level of enzyme activity, both in vivo and in vitro: each increment in dose inhibited the same fraction of enzyme; and the logarithm of the fraction that remained active decreased linearly with increasing dose.