In vitro protection of plasma cholinesterases by metoclopramide from inhibition by mipafox. 2004

G Petroianu, and F Kühn, and K Arafat, and K Zuleger, and A Missler
United Arab Emirates University, Department of Pharmacology and Therapeutics, PO Box 17666, Al Ain, United Arab Emirates. georg.petroianu@uaeu.ac.ae

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 micro M 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.

UI MeSH Term Description Entries
D007531 Isoflurophate A di-isopropyl-fluorophosphate which is an irreversible cholinesterase inhibitor used to investigate the NERVOUS SYSTEM. DFP,Diisopropylfluorophosphate,Fluostigmine,Bis(1-methylethyl) Phosphorofluoridate,Di-isopropylphosphorofluoridate,Diisopropylphosphofluoridate,Dyflos,Floropryl,Fluorostigmine,Di isopropylphosphorofluoridate
D008787 Metoclopramide A dopamine D2 antagonist that is used as an antiemetic. 4-Amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide,Cerucal,Maxolon,Metaclopramide,Metoclopramide Dihydrochloride,Metoclopramide Hydrochloride,Metoclopramide Monohydrochloride,Metoclopramide Monohydrochloride, Monohydrate,Primperan,Reglan,Rimetin,Dihydrochloride, Metoclopramide,Hydrochloride, Metoclopramide,Monohydrochloride, Metoclopramide
D002800 Cholinesterase Inhibitors Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. Acetylcholinesterase Inhibitor,Acetylcholinesterase Inhibitors,Anti-Cholinesterase,Anticholinesterase,Anticholinesterase Agent,Anticholinesterase Agents,Anticholinesterase Drug,Cholinesterase Inhibitor,Anti-Cholinesterases,Anticholinesterase Drugs,Anticholinesterases,Cholinesterase Inhibitors, Irreversible,Cholinesterase Inhibitors, Reversible,Agent, Anticholinesterase,Agents, Anticholinesterase,Anti Cholinesterase,Anti Cholinesterases,Drug, Anticholinesterase,Drugs, Anticholinesterase,Inhibitor, Acetylcholinesterase,Inhibitor, Cholinesterase,Inhibitors, Acetylcholinesterase,Inhibitors, Cholinesterase,Inhibitors, Irreversible Cholinesterase,Inhibitors, Reversible Cholinesterase,Irreversible Cholinesterase Inhibitors,Reversible Cholinesterase Inhibitors
D002802 Cholinesterases Acylcholineacylhydrolase,Cholase,Cholinesterase
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004336 Drug Antagonism Phenomena and pharmaceutics of compounds that inhibit the function of agonists (DRUG AGONISM) and inverse agonists (DRUG INVERSE AGONISM) for a specific receptor. On their own, antagonists produce no effect by themselves to a receptor, and are said to have neither intrinsic activity nor efficacy. Antagonism, Drug,Antagonisms, Drug,Drug Antagonisms
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D018492 Dopamine Antagonists Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. Dopamine Antagonist,Dopamine Blocker,Dopamine Receptor Antagonist,Dopamine Receptor Antagonists,Dopaminergic Antagonist,Dopaminergic Antagonists,Antagonists, Dopamine,Antagonists, Dopamine Receptor,Antagonists, Dopaminergic,Dopamine Blockers,Antagonist, Dopamine,Antagonist, Dopamine Receptor,Antagonist, Dopaminergic,Blocker, Dopamine,Blockers, Dopamine,Receptor Antagonist, Dopamine,Receptor Antagonists, Dopamine
D020128 Inhibitory Concentration 50 The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture. IC50,Concentration 50, Inhibitory
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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