Effects of Administration of an Organo-phosphorus Compound as an Antibilharzial Agent, with Special Reference to Plasma Cholinesterase

Hanna, S Laila; Basmy, K; Selim, Osaima; Shoeb, S. M.; Awny, A. Y.

doi:10.1136/bmj.1.5500.1390

Cited by 19 publications

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References 3 publications

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“…The organophosphorus derivative metrifonate (O,O-dimethyl-2,2,2, trichloro-lhydroxyethylphosphonate; Dipterex; Trichlorfon) is effective in the treatment of human urinary schistosomiasis caused by Schistosoma haematobium, but lacks activity in animals and human subjects infected with Schistosoma mansoni (Beheyt, LeBrun, Cerf, Dierickx & Degroote, 1961;Cerf, LeBrun & Dierickx, 1962; Abdalla, Saif, Taha, Ashmawy, Tawfik, Abdel-Fattah, Sabet & AbdelMeguid, 1965;Hanna, Basmy, Selim, Shoeb & Awny, 1966;Forsyth & Rashid, 1967;Katz, Pellegrino & Pereira, 1968; Davis & Bailey, 1969). Since many organophosphorus compounds are potent inhibitors of various cholinesterases and since there is evidence that acetylcholine may be a humoral neurotransmitter in Inhbition of schistosme cholinesterases schisto (Somes (3ueding, 1952;Barker, Bueding & Timms, 1966) on schistosome cholinesterases were studied.…”

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confidence: 99%

Inhibition by metrifonate and dichlorvos of cholinesterases in schistosomes

Bueding

Liu

Rogers

1972

British J Pharmacology

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Summary1. No species differences between Schistosoma haematobium and Schistosoma mansoni were detected when the 150 of metrifonate for the acetylcholinesterases (AChE) and the cholinesterases (ChE) of these two trematodes were determined in isolated enzyme preparations or following exposure of the intact worms to this drug in vitro. 2. S. haematabium appeared to be more affected by AChE inhibition because, after administration of metrifonate to hamsters, a hepatic shift of the parasites was observed with a dose of metrifonate (150 mg (0-6 mmol) per kg) which produced no shift of S. mansoni, although AChE inhibition was comparable in both species. 3. Administration of a possible metabolite of metrifonate, dichlorvos, to hamsters resulted in a greater inhibition of AChE and ChE activities of S. haematobium than those of S. mansoni. Furthermore, when schistosomes were incubated with dichlorvos, inhibition of AChE activity of female S. haematobium was significantly greater (P<0 005) than that of both sexes of S. mansoni and of male S. haematobium. 4. The discrepancy between the lack of a significant chemotherapeutic effect of metrifonate in hamsters infected with S. haematobium and the clinical results obtained with this organophosphorus compound in human schistosomiasis haematobium is discussed, and the need to conduct similar studies in primates is pointed out.

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Section: Introductionmentioning

confidence: 99%

Inhibition by metrifonate and dichlorvos of cholinesterases in schistosomes

Bueding

Liu

Rogers

1972

British J Pharmacology

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Metrifonate

et al. 1978

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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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Transformation and action of metrifonate

et al. 1978

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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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Effects of Administration of an Organo-phosphorus Compound as an Antibilharzial Agent, with Special Reference to Plasma Cholinesterase

Cited by 19 publications

References 3 publications

Inhibition by metrifonate and dichlorvos of cholinesterases in schistosomes

Inhibition by metrifonate and dichlorvos of cholinesterases in schistosomes

Metrifonate

Transformation and action of metrifonate

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