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In vitro protection of plasma cholinesterases by metoclopramide from inhibition by mipafox
Author(s) -
Petroianu G.,
Kühn F.,
Arafat K.,
Zuleger K.,
Missler A.
Publication year - 2004
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.964
Subject(s) - cholinesterase , chemistry , metoclopramide , pharmacology , organophosphate , in vivo , agonist , medicine , receptor , biochemistry , biology , microbiology and biotechnology , pesticide , agronomy , vomiting
Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition MCP is a reversible inhibitor of cholinesterases from human central nervous system and blood. Metoclopramide may have a cholinesterase protective effect against inhibition by organophosphates. The purpose of the study was to quantify in vitro , by means of the ic 50 shift, the extent of MCP conferred protection, using mipafox (MPFX) as an inhibitor. Mipafox is a neuropathic organophosphate. Cholinesterase activities (with acetylthiocholine [ChE‐A] and butyrylthiocholine [ChE‐B] as substrates) in human plasma were measured photometrically in the presence of different MPFX concentrations and the ic 50 was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the shift induced by the presence of MCP increases with the MCP concentration in a linear manner. In the presence of a clinically easily achievable plasma concentration of 1 µM MCP, the ic 50 of MPFX for cholinesterase ‘shifts’ by a factor of ca. 3–6. The protective effect of MCP on cholinesterase could be of practical relevance in the treatment of organophosphate poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted. Copyright © 2004 John Wiley & Sons, Ltd.