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Metrifonate

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Abstract

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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  1. Marianne Sandoz

    Present address: Laboratoire de Pharmacologie, Hopital de Besançon, Place Saint Jacques, F-25000, Besançon, France

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  1. Department of Toxicology, Swedish Medical Research Council, Karolinska Institutet, S-104 01, Stockholm, Sweden

    Bo Holmstedt, Ingrid Nordgren & Marianne Sandoz

  2. AB Kabi, S-11287, Stockholm, Sweden

    Anders Sundwall

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Holmstedt, B., Nordgren, I., Sandoz, M. et al. Metrifonate. Arch. Toxicol. 41, 3–29 (1978). https://doi.org/10.1007/BF00351766

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