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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Mechanism of Organophosphates (Nerve Gases and Pesticides) and Antidotes: Electron Transfer and Oxidative Stress

Author(s): Peter Kovacic

Volume 10, Issue 24, 2003

Page: [2705 - 2709] Pages: 5

DOI: 10.2174/0929867033456314

Price: $65


Evidence indicates that nerve gas toxins operate in ways in addition to inhibition of acetylcholine esterase. Alternative bioactivities are discussed with focus on electron transfer. The main class, including pralidoxime (2-PAM), incorporates conjugated iminium and oxime moieties that are electron affinic. Various physiological properties of iminium and oxime species are reviewed. The organophosphates encompass both nerve gases and insecticides, possessing similar properties, but different activities. Toxic manifestations are apparently due, in part, to oxidative stress. Alkylation of DNA takes place which may lead to generation of reactive oxygen species. Structure-activity relationships are examined, including reduction potentials and the captodative effect.

Keywords: organophosphates, nerve gas, nerve gas antidotes, pralidoxime, reduction potentials

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