Metrifonate

Metrifonate [52-68-6] (24) is itself not an AChE inhibitor, but is none2ymaticaIly converted into an active irreversible inhibitor of the en2yme. The compound is relatively specific for AChE over butyrylcholinesterase (135) and the irreversible nature of its inhibition gives rise to an extended duration of action. Some clinical experience has been gained through its use to treat schistosomiasis (136,137) and it is undergoing clinical evaluation for AD. 

Metrifonate. This organosphosphoms compound (3), C4HgCl2P04, was first used as an insecticide. 

In the body, metrifonate converts to the active metaboUte dichlorvos, (2,2-dichlorovinyl dimethyl phosphate), which is responsible for the inhibition of the enzyme acetylcholinesterase in the susceptible worm. This effect alone is unlikely to explain the antischistosomal properties of metrifonate (19). Clinically, metrifonate is effective only against infection caused by S. haematobium. Metrifonate is administered in three doses at 2-wk intervals (17). The dmg is well tolerated. Side effects such as mild vertigo, nausea, and cramps are dose-related. This product is not available in the United States. The only manufacturer of metrifonate is Bayer A.G. of Leverkusen, Germany. 

Metrifonate Chiralpak AS 2 mM NH4AC in n-heptane EtOH (75 25) Blood 5.0pg/L [133]... 

Lopez-Arrieta JM, Schneider L. Metrifonate for Alzheimer s disease. Cochrane Database Syst Rev 2006. 

Metrifonate is an organophosphorous compound that is effective only in the treatment of S. haematobium The active metabolite, dichlorvos, inactivates acetylcholinesterase and potentiates inhibitory cholinergic effects. The schistosomes are swept away from the bladder to the lungs and are trapped. Therapeutic doses produce no untoward side effects except for mild cholinergic symptoms. It is contraindicated in pregnancy, previous insecticide exposure, or with depolarizing neuromuscular blockers. Metrifonate is not available in the United States. 

Metrifonate (9.121), an organophosphate compound, is a low-cost antihelminthic used to treat Schistosoma hematobium infections. The drug appears to alter cholinesterase activity in the nematode, temporarily paralysing the adult worm and causing the worm to die. Because of its activity against the cholinesterase enzyme, this drug has also been evaluated as a treatment for Alzheimer s disease. 

Metrifonate is a safe, low-cost alternative drug for the treatment of Schistosoma haematobium infections. It is not active against S mansoni or S japonicum. It is not available in the USA. 

Metrifonate, an organophosphate compound, is rapidly absorbed after oral administration. After the standard oral dose, peak blood levels are reached in 1-2 hours the half-life is about 1.5 hours. Clearance appears to be through nonenzymatic transformation to dichlorvos, its active metabolite. Metrifonate and dichlorvos are well distributed to the tissues and are completely eliminated in 24-48 hours. 

In the treatment of S haematobium, an oral dose of 7.5-10 mg/kg is given three times at 14-day intervals. Cure rates on this schedule are 44-93%, with marked reductions in egg counts in those not cured. Metrifonate was also effective as a prophylactic agent when given monthly to children in a highly endemic area, and it has been used in mass treatment programs. In mixed infections with S haematobium and S mansoni, metrifonate has been successfully combined with oxamniquine. 

Metrifonate should not be used after recent exposure to insecticides or drugs that might potentiate cholinesterase inhibition. Metrifonate is contraindicated in pregnancy. 

Oral 100 mg chewable tablets outside the USA, 100 mg/5 mL suspension Metrifonate (trichlorfon, Bilarcil)1 Niclosamide (Niclocide)1 Oxamniquine (Vansil, Mansil)1... 

FIGURE 12-30. Alzheimer s disease pharmacy. Currently, donepezil is first-line for memory loss, and atypical antipsychotics (SDA) are first-line for positive psychotic symptoms together they may work synergistically. Soon the cholinesterase inhibitors metrifonate and/or rivastigmine may become available. Second-line treatments are tacrine for memory and conventional antipsychotics (D2) for positive psychotic symptoms. Several other agents are in clinical and preclinical development. 

Schmahl, G. and Taraschewski, H. (1 987) Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCI and metrifonate on monogenea (Cyrodactylus aculeati, Diplozoon paradoxum). Parasitology Research 73, 341-351. 

The Ar-(5-nitro-2-furfurylidene)aminotetrahydro-2-( 17/)-pyrimidone developed in China has exhibited both macro- and microfilaricidal activity in humans against lymphatic filariasis [56, 57]. Besides these compounds, various other drugs such as amodiaquine, primaquine, furazolidone and metrifonate, also have been tested as filaricidal in humans and were found to be ineffective [58] however, levamisole [38, 59] has demonstrated some micro- and macrofilaricidal effects in humans at 100 mg/kg, but it is less effective than DEC and produces more severe side-effects. The mode of action of several antifilarial drugs has also been investigated and reviewed by Rew and Fetterer [60] and Subrahmanyam [38]. 

Metrifonate, an organophosphate compound, is rapidly absorbed after oral administration. 

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