| Identification | Back Directory | [Name]
Chlorophos | [CAS]
52-68-6 | [Synonyms]
DEP
DETF
Danex
Dylox
Dyrex
Dyvon
Tugon
wec50
WEC 50
Trinex
ANTHON
Proxol
Soldep
Loisol
oms800
Combot
aerol1
briten
Briton
METRIP
NADPH-D
-TPNH-d
DIPEREX
Lepidex
britten
Cekufon
chlorak
Bovinox
depthon
dimetox
Forotox
Masoten
Mazoten
Neguron
Neguvon
nevugon
Sotipox
Thylate
Ricifon
Votexit
Wotexit
DYREX(R)
Dipterex
Ritsifon
Trametan
leivasom
Foschlor
ent19763
Diptevur
Ditrifon
Dipterax
Dipteres
ciclosom
Clorofos
Bilarcil
chlorfos
bay15922
-NADPH-d
Dylox[R]
TUGON(R)
DIPITEREX
BAY 15922
denkaphon
foschlorr
ent19,763
Phoschlor
CHLOROFOS
Volfartol
DYLOX (TM)
chlorophos
satox20wsc
Metifonate
NCI-C54831
dipterex50
ENT 19,763
Equino-Aid
foschlor25
Foschlorem
Foschlor R
bayerl1359
DITRIFON50
TRICHLOFON
NEGUVON(R)
TRICHLORFON
Trichlorfor
BAYER 15922
chlorophose
Chloroftalm
Agroforotox
bayerl13/59
ditriphon50
Dipterex 50
Khloroftalm
METRIFONATE
DIPTEREX(R)
Polfoschlor
tugonflybait
Trichloorfon
foschlorr-50
Hypodermacid
phoschlorr50
combotequine
dicontalfort
Bayer L 1359
Chloroxyphos
Metriphonate
TRICHLORPHON
TRICHLOROFON
Trichlorfon 0
Chlorophthalm
Bayer L 13/59
Foschlor R-50
Fliegenteller
Trichlorophon
trichlorphene
BAYER L 13/57
trichlorphonfn
Phoschlor R.50
dimethyl ester
Trichlorphon FN
DEP (Pesticide)
tugonstablespray
methylchlorophos
DYLOX, 1GM, NEAT
Trichlorphon S.P.
Methyl Chlorophos
vermicidebayer2349
foschlorem(polish)
dylox-metasystox-r
Chlorophosciclosom
trichlorphon (bsi)
Trichlorphon,powder
Trichlorfon (200 mg)
Parathion-methyl,E.C.
trichlorfon (bsi,iso)
Trichlorphon E.C.(30%)
Dylox (TM) 1g [52-68-6]
Trichlorfon- methoxyl-D6
Metrifonatum purification
Trichlorphon,powder (2.5%)
Dihydro-codehydrogenase II-d
TRICHLORPHON PESTANAL, 250 MG
Trichlorphon Solution, 100ppm
2,2,2-trichloroethyldimethylphosphate
dimethyltrichlorohydroxyethylphosphonate
Dimethyl (trichlorohydroxyethyl)phosphonate
2,2,2-trichloro-1-dimethoxyphosphoryl-ethanol
o,odimetil2,2,2-trichloro1hidroxietilfosfonato
(2,2,2-Trichloro-1-hydroxyethyl)phosphonic acid
dimethyl1-hydroxy-2,2,2-trichloroethylphosphonate
o,o-dimethyl-1-oxy-2,2,2-trichloroethylphosphonate
O,O-Dimethyl (1-oxy-2,2,2-trichloroethyl)phosphonate
Dimethyl (1-hydroxy-2,2,2-trichloroethyl)phosphonate
(2,2,2-TRICHLORO-1-HYDROXY ETHYL)*PHOSPH ONIC ACID D
-Nicotinamide-adenine-dinucleotide-phosphoric Acid-d
O,O-DIMETHYL-1-HYDROXY-2,2,2-TRICHLOROETHYL PHOSPHATE
((2,2,2-trichloro-1-hydroxyethyl)dimethylphosphonate)
O,O-Dimetil-(2,2,2-tricloro-1-idrossi-etil)-fosfonato
O,O-Dimethyl-(1-hydroxy-2,2,2-trichlorathyl)-phosphat
O,O-Dimethyl (2,2,2-trichlorohydroxyethyl)phosphonate
DIMETHYL (2,2,2-TRICHLORO-1-HYDROXYETHYL)-PHOSPHONATE
o,o-dimethyl(2,2,2-trichloro-1-hydroxyethyl)phosponate
[(2,2,2-Trichloro-1-hydroxyethyl) dimethylphosphonate]
1-hydroxy-2,2,2-trichloro-ethylephosphonatededimethyle
O,O-DIMETHYL-1-HYDROXY-2,2,2-TRICHLOROETHYLPHOSPHONATE
dimethoxy-2,2,2-trichloro-1-hydroxy-ethylphosphineoxide
o,o-dimethyl-(2,2,2-trichloro-1-idrossi-etil)-fosfonato
O,O-Dimethyl-(2,2,2-trichloor-1-hydroxy-ethyl)-fosfonaat
O,O-Dimethyl-(2,2,2-trichlor-1-hydroxy-aethyl)phosphonat
o,o-dimethyl(2,2,2-tri-chloro-1-hydroxyethyl)phosphonate
O,O-Dimethyl (2,2,2-trichloro-1-hydroxyethyl)phosphonate
dimethoxy-2,2,2-trichloro-1-hydroxy-ethyl-phosphineoxide
Dimethoxy-(2,2,2-trichloro-1-hydroxyethyl)phosphine oxide
1-hydroxy-2,2,2-trichloroethylphosphonicaciddimethylester
1-Hydroxy-2,2,2-trichloro-ethyle phosphonate de dimethyle
O,O-DiMethyl-(2,2,2-trichloro-1-hydroxhethyl-)phosohonate
O,O-Dimethyl-1-hydroxy-2,2,2-trichloroethylphosphonate,98%
(1-hydroxy-2,2,2-trichloroethyl)-phosphonicacidimethylester
(2,2,2-Trichloro-1-hydroxyethyl)phosphonate, dimethyl ester
(2,2,2-trichloro-1-hydroxyethyl)-phosphonicacidimethylester
Phosphonicacid,(2,2,2-trichloro-1-hydroxyethyl)-,dimethylester
o,o-dimethyl-2,2,2-trichloro-1-hydroxy-ethyl-phosphonate ester
(2,2,2-TRICHLORO-1-HYDROXYETHYL)PHOSPHONIC ACID DIMETHYL ESTER
(1-Hydroxy-2,2,2-trichloroethyl)phosphonic acid, dimethyl ester
o,o-dimethyl-(1-hydroxy-2,2,2-trichloraethyl)phosphonsaeureester
O,O-Dimethyl-(1-hydroxy-2,2,2-trichloraethyl)phosphosaeure ester
Phosphonic acid, (1-hydroxy-2,2,2-trichloroethyl)-, dimethyl ester
Phosphonic acid, (2,2,2-trichloro-1-hydroxyethyl)-, dimethyl ester
trichlorfon (ISO) dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate
(2,2,2-Trichloro-1-hydroxyethyl)phosphonic acid dimethyl ester, Metrifonate
(2,2,2-Trichloro-1-hydroxyethyl)phosphonic acid dimethyl ester, Metrifonate, Trichlorfon
O,O-Dimethyl-1-hydroxy-2,2,2-trichloroethylphosphonate
Trichlorfon
(2,2,2-Trichloro-1-hydroxyethyl)phosphonic acid
dimethyl ester
Metrifonate
Adenosine 5'-(trihydrogen diphosphate) 2'-(Dihydrogen Phosphate) P'-5'-Ester with (4S)-1,4-Dihydro-1--d-ribofuranosyl-3-pyridine-4-d-carboxamide | [EINECS(EC#)]
200-149-3 | [Molecular Formula]
C4H8Cl3O4P | [MDL Number]
MFCD00055272 | [MOL File]
52-68-6.mol | [Molecular Weight]
257.44 |
| Chemical Properties | Back Directory | [Appearance]
Trichlorfon is a white to pale yellow crystalline solid. | [Melting point ]
77-81 °C
| [Boiling point ]
100°C | [density ]
1.73
| [vapor pressure ]
2.1×10-4Pa (20 °C) | [refractive index ]
1.3439
| [storage temp. ]
2-8°C | [solubility ]
Freely soluble in water, very soluble in methylene chloride, freely soluble in acetone and in ethanol (96 per cent). | [form ]
solid | [pka]
6 (est.) | [color ]
Crystals | [Water Solubility ]
Slightly soluble. 1-5 g/100 mL at 21 ºC | [Merck ]
13,9696 | [BRN ]
1709434 | [Stability:]
Light Sensitive | [IARC]
3 (Vol. 30, Sup 7) 1987 | [NIST Chemistry Reference]
Metrifonate(52-68-6) | [EPA Substance Registry System]
Phosphonic acid, (2,2,2-trichloro-1-hydroxyethyl)-, dimethyl ester(52-68-6) |
| Hazard Information | Back Directory | [Chemical Properties]
white crystals or powder | [Uses]
anticholinergic, urinary incontenance therapy | [Uses]
One of the biologically active forms of nicotinic acid. Differs from NAD by an additional phosphate group at the 2?position of the adenosine moiety. Serves as a coenzyme of hydrogenases and dehydrogenases. Present in living cells primarily in the r | [Uses]
Trichlorfon is an irreversible organophosophate acetylcholinesterase inhibitor and the prodrug of Dichlorvos (D435950). Trichlorfon have also shown potential actions to be utilized as an effective org
anophosphorus pesticide. | [Definition]
ChEBI: A phosphonic ester that is dimethyl phosphonate in which the hydrogen atom attched to the phosphorous is substituted by a 2,2,2-trichloro-1-hydroxyethyl group. | [General Description]
Chlorophos is a white crystalline solid. Chlorophos is a wettable powder. Chlorophos can cause illness by inhalation, skin absorption and/or ingestion. Chlorophos is used as a pesticide. | [Air & Water Reactions]
Chlorophos decomposes at higher temperatures in water and at pH <5.5. Chlorophos is sensitive to prolonged exposure to moisture. Chlorophos is unstable in alkaline solutions. | [Reactivity Profile]
Chlorophos is incompatible with alkalis. Chlorophos is corrosive to black iron and mild steel. Chlorophos is corrosive to metals. Chlorophos is subject to hydrolysis. | [Health Hazard]
INHALATION, INGESTION, AND SKIN ABSORPTION. Inhibits cholinesterase. Headache, depressed appetite, nausea, miosis are symptoms of light exposures. Moderate effects are peritoneal paralysis, diarrhea, salivation, lacrimation, sweating, dyspnea, substernal tightness, slow pulse, tremors, muscular cramps and ataxia. Severe symptoms are: pyrexia, cyanosis, pulmonary edema, areflexia, loss of sphincter control, paralysis, coma, heart block, shock and respiratory failure. EYES: Increases permeability of blood vessels in anterior eye. Reduces corneal sensitivity with glaucoma, abnormalities in intraocular tension or decreased visual acuity. | [Fire Hazard]
Combustible material: may burn but does not ignite readily. Containers may explode when heated. Runoff may pollute waterways. Substance may be transported in a molten form. | [Potential Exposure]
Trichlorfon is used as an agricultural and forest insecticide. | [First aid]
If this chemical gets into the eyes, remove any contact lenses at once and irrigate immediately for at least 15 minutes, occasionally lifting upper and lower lids. Seek medical attention immediately. If this chemical contacts the skin, remove contaminated clothing and wash immediately with soap and water. Speed in removing material from skin is of extreme importance. Shampoo hair promptly if contaminated. Seek medical attention immediately. If this chemical has been inhaled, remove from exposure, begin rescue breathing (using universal precautions, including resuscitation mask) if breathing has stopped and CPR if heart action has stopped. Transfer promptly to a medical facility. When this chemical has been swallowed, get medical attention. Give large quantities of water and induce vomiting. Do not make an unconscious person vomit. Medical observation is recommended for 2448 hours after breathing overexposure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a drug or other inhalation therapy. | [Shipping]
UN2783 Organophosphorus pesticides, solid, toxic, Hazard Class: 6.1; Labels: 6.1-Poisonous materials. | [Incompatibilities]
This chemical may be characterized as an organo-phosphate or-chlorine compound. Organophosphates are susceptible to formation of highly toxic and flammable phosphine gas in the presence of strong reducin g agents such as hydrideds and active metals. Partial oxidation by oxidizing agents may result in the release of toxic phosphorus oxides.Alkaline materials: lime, lime sulfur, etc. Corrosive to iron, steel and possibly to other metals. | [Description]
Trichlorfon is a colorless crystalline powder.
It is soluble in water (120 g/L) and most organic solvents,
except aliphatic hydrocarbons. Log Kow = 0.43. Trichlorfon
is rapidly converted to dichlorvos by alkalis (2) and then
hydrolyzed; DT50 (22 ?C) values at pH 4, 7, and 9 are 510 d,
46 h, and <30 min, respectively. | [Waste Disposal]
Add a combustible solvent and burn in a furnace equipped with an afterburner and an alkali scrubber.In accordance with 40CFR165, follow recommendations for the disposal of pesticides and pesticide containers. Must be disposed properly by following package label directions or by contacting your local or federal environmental control agency, or by contacting your regional EPA office. | [Antimicrobial activity]
Useful activity is restricted to Schistosoma haematobium. It
has little activity against other schistosomes.
Although it exhibits activity against several other helminths, it
is not used for their treatment. | [Agricultural Uses]
Insecticide, Anthelmintic: Not approved for use in EU countries
. Registered
for use in the U.S. except California. Trichlorfon has
non-agriculture uses on golf course turf, home lawns and
similar venues, and in non-food contact areas of food and
meat processing plants. Also on ornamental shrubs and
plants, and ornamental and bait fish ponds. Overseas, trichlorfon is used as cattle pour-on, which is classified as a
food-use. It is used against insects such as lepidopteran larvae (caterpillars), white grubs, mole crickets, cattle lice, sod
webworms, leaf miners, stink bugs, flies, ants, cockroaches,
earwigs, crickets, diving beetles, water scavenger beetles,
water boatman, backswimmers, water scorpions, giant water bugs and pillbugs. All food and feed uses in the U.S.
were voluntarily canceled November 21, 1995. It was used
on Brussels sprouts, barley, beets, blueberries, beans (dryand snap), corn, field corn, popcorn, sweet corn, cotton,
cow peas, lima beans, tomatoes, cabbage, carrots (including
tops), cauliflower, collards, cowpeas, southern peas, blackeyed peas, crowder peas, pumpkins, collards, lettuce and
alfalfa, cotton, peanuts, peppers, pumpkins, tobacco, soybeans and treatment to manure.
U.S. Maximum Allowable Residue Levels for the residues
of Trichlorfon [40 CFR 180.198]: in or on the following
raw agricultural commodities: cattle, fat 0.1ppm (negligible residue); cattle, meat byproducts 0.1ppm (negligible
residue); and cattle, meat 0.1ppm (negligible residue) | [Pharmaceutical Applications]
An organophosphorus compound. It is soluble in water and
stable at room temperature. At higher temperatures it decomposes
to the insecticide dichlorvos. | [Trade name]
AEROL 1 (PESTICIDE)®;
AGROFOROTOX®; ANTHON®; BAY 15922®;
BAYER 15922®; BAYER L 13/59®; BILARCIL®;
BOVINOX®[C]; BRITON®; BRITTEN®; CEKUFON®;
CHLORAK®; CHLOROFTALM®; CICLO-SOM®;
COMBOT®; COMBOT EQUINE®; DANEX®[C];
DEP®; DEPTHON®; DIMETOX®; DIPTEREX®;
DIPTEREX® 50; DIPTEVU®; DITRIFON®; DYLOX®;
DYLOX-METASYSTOX-R®; DYREX®; DYVON®;
EQUINO-ACID®; EQUINO-AID®; FLIBOL E®;
FLIEGENTELLE®; FOROTOX®; FOSCHLOR®;
FOSCHLOR R®; FOSCHLOR R-50®; LEIVASOM®;
LOISOL®; MASOTEN®[C]; MAZOTEN®;
NEGUVON®; NEGUVON A®; PHOSCHLOR R50®;
PROXOL®; RICIFON®; RITSIFON®; SATOX 20WSC®;
SOLDEP®; SOTIPOX®; TRICHLORPHON FN®;
TRINEX®; TUGON®; TUGON FLY BAIT®; TUGON
STABLE SPRAY®; VERMICIDE BAYER 2349®;
VOLFARTOL®; VOTEXIT®; WEC 50®; WOTEXIT® | [Mechanism of action]
In vivo, metrifonate rapidly rearranges to
O,O-dimethyl O-(2,2-dichlorovinyl) phosphate,
which is a potent inhibitor of schistosome acetylcholinesterase.
This paralyzes the parasites because
of the accumulation of acetylcholine,
which functions as inhibitory transmitter .
Trade name: Bilarcil (Bayer). | [Pharmacokinetics]
Metrifonate is rapidly absorbed after oral administration,
achieving a peak concentration in plasma within 1–2 h. It
undergoes chemical transformation to dichlorvos, which is
the active molecule. Dichlorvos is rapidly and extensively
metabolized and excreted mainly in the urine. | [Clinical Use]
Urinary schistosomiasis (especially mass chemotherapy control programs) | [Carcinogenicity]
When rats were fed diets that
contained 0, 50, 100, 200, 250, 400, 500, or 1000 ppm
(equivalent to about 0.5, 12.5, 25, or 50 mg/kg/day) for 17
or 24 months, no treatment-related effects occurred in those
fed 50–250 ppm . Histopathological results suggested
the occurrence of mammary tumors in rats fed 400, 500, and
1000 ppm. In another study, when rats were fed diets containing
0, 50, 250, 500, or 1000 ppm (equivalent to about 2.5,
12.5, 25, or 50 mg/kg/day) trichlorfon for 24 months, no
treatment-related effects other than whole-blood cholinesterase
depression at 1000 ppm occurred . There was no
increase in the incidence of either benign or malignant
tumors, including mammary tumors. | [Environmental Fate]
Soil. Trichlorfon degraded in soil to dichlorvos (alkaline conditions) and desmethyl
dichlorvos (Mattson et al., 1955).
Plant. In cotton leaves, the metabolites identified included dichlorvos, phosphoric acid,
O-demethyl dichlorvos, O-demethyl trichlorfon, methyl phosphate and dimethyl phosphate
(Bull and Ridgway, 1969). Chloral hydrate and trichloroethanol were r
Pieper and Richmond (1976) studied the persistence of trichlorfon in various foliage
following an application rate of 1.13 kg/ha. Concentrations of the insecticide found at day
0 and 14 were 81.7 ppm and 7 ppb for willow foliage, 12.6 ppm and 670 ppb for
Chemical/Physical. At 100°C, trichlorfon decomposes to chloral. Decomposed by hot
water at pH <5 forming dichlorvos (Worthing and Hance, 1991). | [Metabolic pathway]
The metabolism of trichlorfon has been reviewed by Zayed et al. (1967),
Sawicki (1973) and Zayed (1974). Trichlorfon is a non-systemic insecticide
with favourable mammalian toxicity. There is considerable evidence
that trichlorfon requires in vivu activation via dehydrochlorinatation to
yield dichlorvos which is the active acetylcholinesterase inhibitor. This
reaction is quite facile in slightly basic solution and the subsequent
routes for the metabolism of trichlorfon are apparently the same as those
of dichlorvos. However, there has been considerable controversy on the
role played by this reaction in vivu since many workers have failed to
identify dichlorvos as a metabolite in plants, mammals or insects treated
with trichlorfon. It was realised that trichlorfon was a very much poorer
inhibitor of acetylcholinesterase than dichlorvos and most considered
that its insecticidal activity must be due to metabolism to dichlorvos as
an activating step in an analogous way that phosphorothioates are
metabolised to phosphates. Metcalf et al. (1959) and Miyamoto (1959)
proposed that trichlorfon was totally inactive as an inhibitor of acetylcholinesterase
and that any inhibition seen in vitru was due to some
conversion to dichlorvos during the course of the assay for anticholinesterase
activity. Metcalf et al. (1959) also reported the identification
of dichlorvos in trichlorfon-treated houseflies. This conclusion was
by no means universal and Arthur and Casida (1957) argued that trichlorfon
was the active acetylcholinesterase inhibitor and the identification
of a glucuronide conjugate of trichloroethanol was evidence that the
primary route of stage I metabolism was hydrolysis of the P< bond.
Other work, however, has provided evidence for the in vivu production of
dichlorvos and it seems probable that the failure of some experiments to
detect it is due to its rapid metabolism, resulting in a very low steadystate
concentration. The metabolism of trichlorfon can be envisaged
as being either through a deactivation route via demethylation and/or
conjugation followed by breakdown of the demethylated products
or an activation reaction to yield dichlorvos which is then degraded
via a hydrolytic mechanism to yield dimethyl phosphate and dichloroacetaldehyde
or demethylated by glutathione-S-methyl transferase.
These competing reactions have been investigated in mammals and
insects and it is the balance of activation and degradative metabolism
which confers the favourable mammalian toxicity of trichlorfon in
comparison with that of dichlorvos. | [Metabolism]
Trichlorfon administered to mammals is rapidly metabolized and excreted almost completely in the
urine within 6 h. Majormetabolites are dimethyl hydrogen
phosphate, methyl dihydrogen phosphate, and conjugates
of dichloroacetic acid and trichloroethanol. Trichlorfon is
rapidly broken down in soil. | [Degradation]
Trichlorfon is subject to hydrolysis and dehydrochlorination. Decomposition
proceeds more rapidly with heating and above pH 6. It is rapidly
converted by alkalis to dichlorvos (2) which is then hydrolysed. DT50 s at pH 4,7 and 9 were 510 days, 46 hours and <30 min respectively at 20 °C.
Photolysis is slow (PM).
Trichlorfon undergoes a facile rearrangement in the presence of mild
base or heat to yield dichlorvos (2) and one mole of HCI (Barthel et al.,
1955; Lorenz et al., 1955; Mattson et al., 1955). This reaction was shown to
be first order in both trichlorfon concentration and [OH-] with a calculated
t1/2 of 5 hours at pH 7.0 (37 °C) (Miyamoto, 1959). A mechanism for
this reaction is shown in Scheme 1. | [Toxicity evaluation]
The acute oral LD50 for rats is about 450 mg/kg.
Inhalation LC50 (1 h) for rats is >0.5 mg/L air. NOEL
(2 yr) for rats is 100 mg/kg diet (5 mg/kg/d). ADI is
0.01 mg/kg b.w. |
| Safety Data | Back Directory | [Hazard Codes ]
Xn,N | [Risk Statements ]
22-43-50/53 | [Safety Statements ]
24-37-60-61-2 | [RIDADR ]
UN 3077 9/PG 3
| [WGK Germany ]
3
| [RTECS ]
TA0700000
| [HazardClass ]
6.1(b) | [PackingGroup ]
III | [HS Code ]
29319090 | [Safety Profile]
Poison by ingestion,
inhalation, inti-aperitoneal, subcutaneous,
intravenous, and intramuscular routes.
Moderately toxic by skin contact. Human
systemic effects: true cholinesterase.
Experimental teratogenic and reproductive
effects. Questionable carcinogen with
experimental carcinogenic and tumorigenic
data. Human mutation data reported. An eye
irritant. When heated to decomposition it
emits very toxic fumes of Cland POx. | [Hazardous Substances Data]
52-68-6(Hazardous Substances Data) | [Toxicity]
LD50 in male, female rats (mg/kg): 630, 560 orally (Gaines) |
| Questions And Answer | Back Directory | [Pharmacology and mechanism of action]
Metrifonate is an organophosphorus compound, first introduced as an insecticide in 1952 and a little later as an anthelminthic. Early clinical studies have reported it to be effective against a wide number of helminthic infections including schistosomiasis, ascariasis, ancylostomiasis, and trichuriasis[1] .The drug has been tried in onchocerciasis with limited success [2]. It is also an experimental drug in Alzheimer’s disease[3]. Today, it is mainly used against Schistosoma (S) haematobium. The mechanism of action of metrifonate is unknown. The only pharmacological action described hitherto is its inhibitory effect on cholinesterases, which is due to its rearrangement product, dichlorvos. Dichlorvos, as a drug is used widely in veterinary medicine and has been given to man as a slow release preparation [4, 5]. In vitro, metrifonate paralyses both S. haematobium and S. mansoni [6]. However, clinically it is effective only against S. haematobium. Although this paradox has been explained to be due to the different locations of the two worms in man [7, 8], recent reports suggest that S. haematobium may be more sensitive to metrifonate than S. mansoni because of much higher levels of cholinesterase activity in its tegument [9].
| [Indications]
For the treatment of Schistosoma haematobium infections. During mass treatment programmes, when cost is a major factor, metrifonate may be preferred over praziquantel. When radical treatment is desired and cost is not a problem, praziquantel is the first drug of choice, i.e. in places where re-infection is not expected.
| [Side effects]
Despite extensive toxicological and clinical studies no major side effects have been observed with the recommended dose[10, 11]. One of the most important side effects of the drug, is its effect on blood cholinesterases. Soon after its intake, both plasma and erythrocyte cholinesterase levels are inhibited to zero and to 80%, respectively. Normal plasma cholinesterase levels return after 4 weeks, but it takes longer for the recovery of the erythrocyte cholinesterase [12]. Although no correlation seems to exist between the dose and the degree of cholinesterase inhibition, a good relationship was found between the occurrence of side effects and the plasma levels of the drug [13]. Side effects commonly reported include nausea, vomiting, headache, abdominal pain, vertigo, and fatigue. They are low in frequency and severity and they usually disappear spontaneously within a few hours after drug intake.
In the case of metrifonate intoxication, pralidoxime iodide is used as an antidote (1 g is injected intravenously in 2 minutes. The dose may be repeated after 20 minutes if symptoms persist). In addition, atropine should be given in high doses, i.e. 2–4 mg i.v. every 3–10 minutes to a maximum daily dose of 50 mg.
| [Contraindications]
Metrifonate should not be given to patients taking suxamthonium. In areas where organophosphorus insecticides have been sprayed, the community may already have low levels of blood cholinesterases. Special precautions are needed in such situations.
| [Interactions]
Metrifonate prolongs the muscle-relaxing effect of succinylcholine. | [Preparations]
• Bilarcil® (Bayer). Tablets 100 mg.
| [References]
1. Cerf J, Lebrun A, Dierichx J (1962). A new approach to helminthiasis control: The use of an organophosphorus compound. Am J Trop Med Hyg, 11, 514–517.
2. Awadzi K, Gilles HM (1980). The chemotherapy of onchocerciasis, III: a comparative study of diethylcarbamazine DEC and metrifonate. Ann Trop Med Parasitol, 74, 210–217.
3. Moriearty PL, Womack CL, Dick BW, Colliver JA, Robbs RS, Becker RE (1991). Stability of peripheral hematological parameters after chronic acetylcholinesterase inhibition in man. Am J Hematol, 37, 280–282.
4. Cervoni WA, Oliver-Gonzalez J, Kaye S, Slomka MB (1969). Dichlorvos as a single-dose intestinal anthelminthic therapy for man. Am J Trop Med Hyg, 18, 912–919.
5. Chavarria APA, Swartzwelder JC, Villarejos VM, Kotcher E, Arguedas J (1969). Dichlorvos, an effective broad spectrum anthelminthic. Am J Trop Med Hyg, 18, 907–911.
6. Bueding E, Liu CL, Rogers SH (1972). Inhibition by metrifonate and dichlorvos of cholinesterases in schistosomes. Br J Pharmacol, 46, 480–487.
7. Forsyth DM, Rashid C (1967). Treatment of urinary schistosomiasis with trichlorofon. Lancet, ii, 909–912.
8. Feldmeier H, Doehring E, Daffalla AA, Omer AHS, Dietrich M (1982). Efficacy of metrifonate in urinary schistosomiasis: Comparison of reduction of Schistosoma haematobium and S. mansoni eggs. Am J Trop Med Hyg, 31, 1188–1194.
9. Camacho M, Tarrab-Hazdai R, Espinoza B, Arnon R, Agnew A (1994). The amount of acetylcholinesterase on the parasite surface reflects the differential sensitivity of schistosome species to metrifonate. Parasitology, 108, 153–160.
10. Holmstedt B, Nordgren I, Sandoz M, Sundwall A (1978). Metrifonate: Summary of toxicological and pharmacological information available. Arch Toxicol, 41, 3–29.
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