In vitro protection of red blood cell acetylcholinesterase by metoclopramide from inhibition by organophosphates (paraoxon and mipafox)

Georg Petroianu, Kholoud Arafat, Melita Kosanovic, Ayman Saleh, Vijayasarathy Camasamudram, Mohamed Y. Hasan

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)

    Abstract

    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 the human central nervous system and blood, and may have a red blood cell (RBC) acetylcholinesterase (AChE) protective effect against inhibition by organophosphates. The purpose of the study was to quantify 'in vitro', by means of the IC50 shift, the extent of MCP conferred protection, by using paraoxon (POX) and mipafox (MPFX) as inhibitors. Paraoxon is a widely used non-neuropathic organophospate responsible for a large number of accidental or suicidal exposures. Mipafox is a neuropathic organophospate. Red blood cell AChE activities in human plasma were measured photometrically in the presence of different POX, MPFX and MCP concentrations and the IC50 was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the IC50, shift induced by the presence of MCP increases with the MCP concentration in a linear manner. The protective effect of MCP on cholinesterases could be of practical relevance in the treatment of POX and MPFX poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted.

    Original languageEnglish
    Pages (from-to)447-451
    Number of pages5
    JournalJournal of Applied Toxicology
    Volume23
    Issue number6
    DOIs
    Publication statusPublished - Nov 1 2003

    Keywords

    • Cholinesterase
    • Metoclopramide
    • Organophosphate
    • Pralidoxime

    ASJC Scopus subject areas

    • Toxicology

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