Metrifonate

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.

Donepezil Hydrochloride (E2020) and Other Acetylcholinesterase Inhibitors

“…The interim results obtained from Phase II study confirm earlier reports that galanthamine holds promise as an effective and well-tolerated treatment for cognitive impairment in patients with SDAT [37]. inhibition over time [38]. Metrifonate has a short plasma half-life but has a long duration of action in the brain.…”

Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation

“…Generally, DjChE was similarly sensitive to the various OPs as mammalian AChE, with bimolecular rate constants varying within approximately an order of magnitude of that reported for human or mouse AChE (Reiner and Radić 2000). Not surprisingly, DjChE showed greater sensitivity than mouse AChE to dichlorvos, the non-enzymatic byproduct of metrifonate, a commonly used schistosomiasis drug (Holmstedt et al 1978). The most potent of the OPs was diazinon oxon.…”

Natural Products as a Source for Treating Neglected Parasitic Diseases

“…In this sense, previous studies on the characterization and inhibition of relevant parasite proteins like acetylcholinesterase [67,157], cysteine protease [158] serine protease [159] and glutamatergic receptors in adult S. mansoni [160] are relevant to the development of new possible methods towards the identification and validation of new targets. For example, Abdulla et al .…”

“…Recent results indicate that following the reduction of the concentration of the drug, S. mansoni is able to go back to the mesenteric veins within the intestine and re-establish the infection. However, S. haematobium adults remain in the lung and are not able to move back to the bladder or urethra veins and re-establish the infection [66,67]. Since metrifonate is only effective against the urogenital disease, the drug is only recommended by the WHO to treat the infection of S. haematobium [68].…”