{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T23:12:03Z","timestamp":1762125123474,"version":"build-2065373602"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,1,24]],"date-time":"2005-01-24T00:00:00Z","timestamp":1106524800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 weak and reversible inhibitor of cholinesterases. We have shown that MCP has a cholinesterase protective effect against inhibition by organophosphates. The putative mode of protective action of MCP is competition for the active site of the enzyme with the more potent organophosphate. In the present paper we present our results using another weak inhibitor of cholinesterases: ranitidine (RAN).<\/jats:p><jats:p>The purpose of the study was to quantify <jats:italic>in vitro<\/jats:italic> the extent of RAN\u2010conferred protection, using paraoxon (POX) as an inhibitor. Paraoxon is a non\u2010neuropathic organophosphate responsible for a large number of accidental or suicidal exposures.<\/jats:p><jats:p>Red blood cell (RBC) acetylcholinesterase (AChE) activities in whole blood and butyrylcholinesterase (BChE) activities in human plasma were measured photometrically in the presence of different POX and RAN concentrations and the <jats:sc>ic<\/jats:sc><jats:sub>50<\/jats:sub> was calculated. Determinations were repeated in the presence of increasing RAN concentrations. The <jats:sc>ic<\/jats:sc><jats:sub>50<\/jats:sub> shift induced by the presence of RAN increases with the RAN concentration in a linear manner. The shift was more pronounced with RBC\u2010AChE.<\/jats:p><jats:p>The protective effect of RAN on cholinesterase could be of practical relevance in the treatment of POX poisoning. We conclude that <jats:italic>in vivo<\/jats:italic> testing of RAN as an organophosphate protective agent is warranted. Copyright \u00a9 2005 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1036","type":"journal-article","created":{"date-parts":[[2005,1,24]],"date-time":"2005-01-24T11:51:00Z","timestamp":1106567460000},"page":"60-67","source":"Crossref","is-referenced-by-count":19,"title":["Weak inhibitors protect cholinesterases from strong inhibitors (paraoxon): <i>in vitro<\/i> effect of ranitidine"],"prefix":"10.1002","volume":"25","author":[{"given":"G. 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