Pre- and post-treatment effect of physostigmine on soman-inhibited human erythrocyte and muscle acetylcholinesterase in vitro

Journal Article · Sun May 15 00:00:00 EDT 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2011.03.005· OSTI ID:21535295

Herkert, N M ^[1]; Schulz, S ^[2]; Wille, T; Thiermann, H ^[1]; Hatz, R A ^[2]; Worek, F ^[1]

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1. Bundeswehr Institute of Pharmacology and Toxicology, Neuherbergstrasse 11, 80937 Munich (Germany)
2. Department of Thoracic Surgery, Asklepios Clinic, Robert-Koch-Allee 2, 82131 Gauting (Germany)

Standard treatment of organophosphorus (OP) poisoning includes administration of an antimuscarinic (e.g., atropine) and of an oxime-based reactivator. However, successful oxime treatment in soman poisoning is limited due to rapid aging of phosphylated acetylcholinesterase (AChE). Hence, the inability of standard treatment procedures to counteract the effects of soman poisoning resulted in the search for alternative strategies. Recently, results of an in vivo guinea pig study indicated a therapeutic effect of physostigmine given after soman. The present study was performed to investigate a possible pre- and post-treatment effect of physostigmine on soman-inhibited human AChE given at different time intervals before or after perfusion with soman by using a well-established dynamically working in vitro model for real-time analysis of erythrocyte and muscle AChE. The major findings were that prophylactic physostigmine prevented complete inhibition of AChE by soman and resulted in partial spontaneous recovery of the enzyme by decarbamylation. Physostigmine given as post-treatment resulted in a time-dependent reduction of the protection from soman inhibition and recovery of AChE. Hence, these date indicate that physostigmine given after soman does not protect AChE from irreversible inhibition by the OP and that the observed therapeutic effect of physostigmine in nerve agent poisoning in vivo is probably due to other factors.

• OSTI ID: 21535295
• Journal Information: Toxicology and Applied Pharmacology, Vol. 253, Issue 1; Other Information: DOI: 10.1016/j.taap.2011.03.005; PII: S0041-008X(11)00091-3; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ATROPINE
ENZYMES
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GUINEA PIGS
HUMAN POPULATIONS
IN VITRO
IN VIVO
INHIBITION
KINETICS
MUSCLES
ORGANIC PHOSPHORUS COMPOUNDS
POISONING
SAFETY
TIME DEPENDENCE
ALKALOIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
DRUGS
MAMMALS
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ORGANIC COMPOUNDS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
POPULATIONS
PROTEINS
RODENTS
VERTEBRATES