ABSTRACT
I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215 II. Current Therapy for Nerve Agent Exposure . . . . . . . . . . . . . . . . . . . . . . . . 217
III. Nerve Agent Bioscavengers: an Alternative to Conventional Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
IV. Stoichiometric Scavengers and the Protection They Offer . . . . . . . . . . . . . 220 A. Antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220 B. Enzymes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 220
V. Catalytic Bioscavengers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228 VI. Behavioral Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
VII. Behavioral Effects of Scavengers Alone . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 VIII. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Acknowledgment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Organophosphorous anticholinesterases (OPs), usually acid anhydride derivatives of phosphoric acid, are among the most toxic substances identified.1 Originally, OP were developed for use as insecticides,2 but their extreme toxicity toward higher vertebrates has led to their adoption as weapons of warfare.3 The OPs most com-
monly utilized as chemical weapons (referred to as nerve agents) are anhydrides of hydrocyanic acid, hydrofluoric acid, or of a derivative of thiocholine: tabun (GA), sarin (GB), soman (GD), cyclohexylmethyl phosphonofluoridate (GF), and ethyl-Sdiisoproplyaminoethyl methylphosphonothioate (VX). Their molecular weights range from 140 to 267 Daltons (Da) and, under standard conditions, they are all liquids that differ in their degrees of volatility.4 They have median lethal dose (LD50) values in mammals, including estimates for humans, in the g/kg dose range for all routes of exposure except dermal, where LD50 doses are in the mg/kg range.
