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In vitro protection of plasma cholinesterases by metoclopramide from inhibition by paraoxon
Author(s) -
Petroianu G.,
Kühn F.,
Thyes C.,
Ewald V.,
Missler A.
Publication year - 2003
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.891
Subject(s) - paraoxon , metoclopramide , pharmacology , chemistry , cholinesterase , organophosphate , pralidoxime , in vivo , agonist , receptor , acetylcholinesterase , medicine , enzyme , biochemistry , biology , vomiting , microbiology and biotechnology , pesticide , agronomy
Metoclopramide (MCP) is a dopamine receptor antagonist and serotonine 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. MCP 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 paraoxon (POX) as an inhibitor. POX is a widely used organophospate responsible for a large number of accidental or suicidal exposures. Cholinesteratic activities (ChE) (with acetyl‐thiocholine (A) and butyryl‐thiocholine (B) as substrates) in human plasma were measured photometrically in the presence of different POX concentrations and 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 POX for ChE ‘shifts’ by a factor of ≈2–3. The protective effect of metoclopramide on cholinesterases could be of practical relevance in the treatment of paraoxon poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted. Copyright © 2003 John Wiley & Sons, Ltd.