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Weak Inhibitors Protect Cholinesterases from Stronger Inhibitors (Dichlorvos): In Vitro Effect of Tiapride

Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

A. Schmitt

Central Institute of Mental Health, Mannheim, Germany

K. Arafat
M. Y. Hasan

Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates

Correspondence: Address correspondence to Georg A. Petroianu, Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17 666, Al Ain, United Arab Emirates. E-mail:georg.petroianu{at}uaeu.ac.ae

Metoclopramide is a benzamide dopamine receptor antagonist and serotonine receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition, metoclopramide is a weak and reversible inhibitor of cholinesterases. The authors have previously shown that metoclopramide has a cholinesterase protective effect against inhibition by organophosphates (OPs). The putative mode of protective action of metoclopramide is, when administered in excess, competion for the active site of the enzyme with the more potent OP. In the present paper the authors present their results using another benzamide with weak cholinesterase inhibitory properties, tiapride (TIA). The purpose of the study was to quantify in vitro the extent of TIA-conferred protection, using dichlorvos (dichlorovinyl dimethyl phosphate; DDVP) as an inhibitor. DDVP is a moderately toxic (LD₅₀ in rats in the milligram range), non-neuropathic OP. The substance is responsible for a large number of accidental or suicidal exposures. 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 DDVP and TIA concentrations and IC₅₀ was calculated. Determinations were repeated in the presence of increasing TIA concentrations. The IC₅₀ of DDVP increases with the TIA concentration in a linear manner. The protective effect of TIA on cholinesterase could be of practical relevance in the treatment of OP poisoning. The authors conclude that in vivo testing of TIA as an OP protective agent is warranted.

Key Words: Cholinesterase • Dichlorvos • Inhibition • Organophosphate • Pralidoxime • Tiapride

International Journal of Toxicology, Vol. 24, No. 2, 79-86 (2005)
DOI: 10.1080/10915810590921360


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