Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The organophosphorus compound 0,0-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate was introduced as an insecticide, trichlorfon, in 1952 (Lorenz et al., 1955) and as a drug, metrifonate, in the treatment of schistosomiasis in 1960 (Lebrun and Cerf, 1960). This organophosphorus compound is unique in that it has been claimed not to be a direct acting cholinesterase inhibitor but being transformed nonenzymatically into an active component dichlorvos, 2, 2-dichlorovinyl dimethyl phosphate (DDVP). The evidence for this transformation has mostly been indirect. Recently it has been proved chemically and quantitatively that this transformation occurs in the animal body (Nordgren et al., 1978). Metrifonate is the sole organophosphorus compound currently studied clinically in schistosomiasis. A substantial therapeutic effect is obtained only in Schistosoma haematobium infections. In this review on available data of metrifonate it is suggested that further more detailed studies of both S. haematobium and S. mansoni are necessary. This should include studies of the enzymic properties of the worms and the reaction of their esterases towards both metrifonate and DDVP as well as the pharmacokinetics of these compounds in man. In addition there are still unsolved discrepancies reported regarding organ toxicity of the compound which may, however, be due to different grades of parity of the test material.
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PMID:Metrifonate. Summary of toxicological and pharmacological information available. 36 95

Metrifonate (0,0-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate) is an organophosphorus compound where there are excellent possibilities to make studies in man. Metrifonate and its rearrangement product dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) were studied in human blood from schistosomiasis patients treated with Bilarcil. A mass fragmentographic technique was employed. Deuterium labelled variants of the substances were used, both as internal standards and to compensate for DDVP formed during the workup procedure. The amount of DDVP in plasma was about 1% of the amount of metrifonate. In erythrocytes the corresponding amount of DDVP in percent of metrifonate was half or less. Both compounds reached peak levels within two hours and were detectable for at least eight hours. The results were compared to erythrocyte and plasma cholinesterase determinations. Levels of metrifonate and DDVP, together with cholinesterase activity, have also been studied in mouse brain, liver and kidney. It is proposed that metrifonate acts as a slow release formulation for DDVP. Clearance of metrifonate in man occurs primarily via DDVP. Mild vertigo subsiding in a few hours was the most common side-effect.
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PMID:Quantitation of metrifonate and dichlorvos in blood and tissues by gas chromatography-mass spectrometry. 718 87

A method for the simultaneous quantitation of metrifonate (0,0-dimethyl-(1-hydroxy-2,2,2-trichloroethyl)-phosphonate) and dichlorvos (2,2-dichlorovinyl dimethyl phosphate, DDVP) in human blood has been worked out. It is based upon multiple labelling of the compounds with deuterium and gas phase analysis using the mass spectrometer as a selective detector. The amount of DDVP in plasma is about 1% of the amount of metrifonate. In erythrocytes the corresponding amount of DDVP is 0.5% or less of metrifonate. Both compounds reach peak levels in blood within two hours after oral dosing and are detectable for at least eight hours. Cholinesterase activity in plasma reaches zero levels within 15 min. and remains inhibited for more than eight hours. Red blood cell cholinesterase is inhibited only 60-80%. According to kinetic calculations, clearance of metrifonate occurs primarily via dichlorvos. If dichlorvos is the only active component, which in all likelihood it is, it's slow release may be important in the schistosomicidal effect. Clinical data in seven metrifonate treated patients revealed that mild vertigo subsiding in a few hours was the most common side effect.
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PMID:Levels of metrifonate and dichlorvos in plasma and erythrocytes during treatment of schistosomiasis with Bilarcil. 734 16