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  • Title: Transformation and action of metrifonate.
    Author: Nordgren I, Bergström M, Holmstedt B, Sandoz M.
    Journal: Arch Toxicol; 1978 Oct 13; 41(1):31-41. PubMed ID: 718420.
    Abstract:
    Chemical formation of dichlorvos (2, 2-dichlorovinyl dimethyl phosphate) was found to occur in mouse brain after i.p. injection of metrifonate (2, 2, 2-trichloro-1-hydroxyethyl dimethyl phosphonate). A mass fragmentographic technique was used. Different isotopic variants were used both as internal standards and to compensate for dichlorvos formed during the workup procedure. The dichlorvos formed in vivo was found to have its maximal concentration a few minutes after the maximum of the metrifonate itself. The effect of metrifonate and dichlorvos on acetylcholine levels, acetylcholinesterase activity and synthesis rate of acetylcholine in mouse brain was also studied. In all three cases the effect of metrifonate was found to be prolonged and delayed as compared to the effect of dichlorvos. It is concluded that metrifonate acts as a slow release formulation in the body giving rise to dichlorvos nonenzymatically. This circumstance at least partly explains its efficacy in the treatment of schistosomiasis.
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