Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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

Author(s): Peter Kovacic.

Abstract:

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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Article Details

VOLUME: 10
ISSUE: 24
Year: 2003
Page: [2705 - 2709]
Pages: 5
DOI: 10.2174/0929867033456314
Price: $58