Holmstedt B, Nordgren I, Sandoz M, Sundwall A
Arch Toxicol. 1978 Oct 13;41(1):3-29. doi: 10.1007/BF00351766.
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.
有机磷化合物0,0 - 二甲基 -(1 - 羟基 - 2,2,2 - 三氯乙基) - 膦酸酯于1952年作为杀虫剂敌百虫被引入(洛伦兹等人,1955年),并于1960年作为药物美曲膦酯用于治疗血吸虫病(勒布伦和塞尔夫,1960年)。这种有机磷化合物的独特之处在于,据称它不是直接作用的胆碱酯酶抑制剂,而是通过非酶促转化为活性成分敌敌畏,即2,2 - 二氯乙烯基二甲基磷酸酯(DDVP)。这种转化的证据大多是间接的。最近已经通过化学和定量方法证明这种转化发生在动物体内(诺德格伦等人,1978年)。美曲膦酯是目前临床上唯一用于研究血吸虫病的有机磷化合物。仅在埃及血吸虫感染中可获得显著的治疗效果。在这篇关于美曲膦酯现有数据的综述中,建议对埃及血吸虫和曼氏血吸虫进行更详细的研究。这应包括对虫体的酶学性质及其酯酶对敌百虫和敌敌畏的反应以及这些化合物在人体内的药代动力学的研究。此外,关于该化合物的器官毒性仍有未解决的差异报道,然而,这可能是由于试验材料的不同纯度等级所致。