Metrifonate

Chemical compound

P02BB01 (WHO) QP52AB01 (WHO) QP53AF02 (WHO)

Pharmacokinetic dataElimination half-life3 hoursIdentifiers

IUPAC name

(RS)-Dimethyl (2,2,2-trichloro-1-hydroxyethyl)phosphonate

CAS Number

52-68-6^Y

PubChem CID

5853

ChemSpider

5644^N

UNII

DBF2DG4G2K

KEGG

C07971^Y

ChEBI

CHEBI:6908^N

CompTox Dashboard (EPA)

DTXSID0021389

ECHA InfoCard100.000.137

Chemical and physical dataFormulaC₄H₈Cl₃O₄PMolar mass257.43 g·mol⁻¹3D model (JSmol)

Interactive image

ChiralityRacemic mixture

SMILES

COP(=O)(C(C(Cl)(Cl)Cl)O)OC

InChI

InChI=1S/C4H8Cl3O4P/c1-10-12(9,11-2)3(8)4(5,6)7/h3,8H,1-2H3^N
Key:NFACJZMKEDPNKN-UHFFFAOYSA-N^N

^NY (what is this?) (verify)

Metrifonate (INN) or trichlorfon (USAN) is an irreversible organophosphate acetylcholinesterase inhibitor.^[3] It is a prodrug which is activated non-enzymatically into the active agent dichlorvos.

It is used as an insecticide. According to the US Environmental Protection Agency trichlorfon has been used on golf course turf, home lawns, non-food contact areas of food and meat processing plants, ornamental shrubs and plants, and ornamental and baitfish ponds. Used to control caterpillars, white grubs, mole crickets, cattle lice, sod webworms, leaf miners, stink bugs, flies, ants, cockroaches, earwigs, crickets, diving beetle, water scavenger beetle, water boatman backswimmer, water scorpions, giant water bugs and pillbugs.^[4] After reregistration, a number of its uses were voluntarily restricted, and currently, it is used in nonfood areas to control flies, roaches, and ants among other pests. Outdoors it is used on ornamental plants, golf courses, and lawn grass to treat lepidopteran larvae pests, it is also used to treat flies in animal husbandry in areas that are not accessible to animals, it also used to control harvester ants.^[5]

It can be used to treat schistosomiasis^[6] caused by Schistosoma haematobium,^[7] but is no longer commercially available.^[8]

It has been proposed for use in treatment of Alzheimer's disease, but use for that purpose is not currently recommended.^[9]

Bans and restrictions

In the United States, trichlorfon/metrifonate may only be used on nonfood and nonfeed sites.^[10]

Trichlorfon/metrifonate was banned in the EU in 2008 (Regulation (EC) 689/2008) and in Brazil in 2010.^[11]

Trichlorfon/metrifonate was banned in Argentina in 2018,^[12] noting that trichlorvon converts to dichlorvos by metabolism in plants, as well as by biodegradation of the soil.

Trichlorfon/metrifonate was banned in New Zealand in 2011.^[13]

Trichlorfon/metrifonate was banned in India from 2020.^[14]

References

^ "Trichlorfon". Haz-Map. U.S. National Library of Medicine. August 2015. Retrieved 2015-10-13.
^ "Metrifonate". U.S. National Institute of Standards and Technology. Retrieved 2016-09-04.
^ "NLH - Neurological Conditions - Metrifonate for Alzheimer's disease". Archived from the original on 2009-07-19.
^ "Trichlorfon Facts". Pesticides: Reregistration. U.S. Environmental Protection Agency.
^ "Trichlorfon". R.E.D. Facts. U.S. Environmental Protection Agency.
^ "Monographs: Pharmaceutical substances: Metrifonate (Metrifonatum)". The International Pharmacopoeia Fourth Edition. WHO. Archived from the original on June 3, 2016. Retrieved 2015-10-20. (dead link 31 January 2019)
^ "Helminths: Schistosomiasis: Metrifonate". WHO Model Prescribing Information: Drugs Used in Parasitic Diseases - Second Edition. WHO. 1995. Archived from the original on July 15, 2010. Retrieved 2015-10-20.
^ Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams GM, McManus DP (April 2002). "Schistosomiasis" (PDF). The New England Journal of Medicine. 346 (16): 1212–20. doi:10.1056/NEJMra012396. PMID 11961151.
^ López-Arrieta JM, Schneider L (April 2006). López-Arrieta J (ed.). "Metrifonate for Alzheimer's disease". The Cochrane Database of Systematic Reviews (2): CD003155. doi:10.1002/14651858.CD003155.pub3. PMID 16625573.
^ "Reregistration Eligibility Decision Trichlorfon" (PDF). Retrieved 2018-08-09.
^ "Decision Guidance Document Trichlorfon - Rotterdam Convention" (PDF). Retrieved 2018-08-09.
^ "Argentina bans dichlorvos and trichlorfon". Retrieved 2018-08-09.
^ "New Zealand bans trichlorfon". Retrieved 2018-08-09.
^ "Banned Pesticides in India". 2018-01-17. Retrieved 2018-08-09.

Pest control: Insecticides

Carbamates

Inorganic compounds

Insect growth regulators

Other chemicals

Antiparasitics – Anthelmintics (P02) and endectocides (QP54)

Antiplatyhelmintic agents

Antitrematodals
(schistosomicides)

Binds tubulin	benzimidazole Triclabendazole^#
AChE inhibitor	phosphonic acid Metrifonate^‡
Other/unknown	quinoline Arpraziquantel Praziquantel^# Oxamniquine^# phenol Bithionol thiazole Niridazole thioxanthone Hycanthone Lucanthone antimony compounds Stibophen Tartar emetic^‡

Anticestodals
(taeniacides)

Binds tubulin	benzimidazole Albendazole^#
Other/unknown	quinoline Praziquantel^# salicylanilide Niclosamide^# aminoacridine Quinacrine butyrophenone Desaspidin chlorophenol Dichlorophen

Antinematodal agents
(including
macrofilaricides)

Binds tubulin	benzimidazole Mebendazole^# Albendazole^# Tiabendazole Fenbendazole Ciclobendazole Flubendazole
Glutamate-gated chloride channel, GABA receptor	avermectins Abamectin Doramectin Emamectin Eprinomectin Ivermectin^# Selamectin milbemycins Moxidectin Milbemycin oxime
NMDA	tetrahydropyrimidine Pyrantel^# pyrantel pamoate Oxantel Morantel Carbantel Febantel (aka felsantel)
Other/unknown	piperazine Piperazine Diethylcarbamazine^# thiazole Levamisole^# quinolinium Pyrvinium benzylammonium Bephenium naphthalenesulfonate Suramin^# Ascaridole^‡ Hexylresorcinol Santonin^‡ Tribendimidine Tetrachloroethylene^‡

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Acetylcholine metabolism and transport modulators

Enzyme
(modulators)

ChATTooltip Choline acetyltransferase	Inhibitors: 1-(-Benzoylethyl)pyridinium 2-(α-Naphthoyl)ethyltrimethylammonium 3-Chloro-4-stillbazole 4-(1-Naphthylvinyl)pyridine Acetylseco hemicholinium-3 Acryloylcholine AF64A B115 BETA CM-54,903 N,N-Dimethylaminoethylacrylate N,N-Dimethylaminoethylchloroacetate
AChETooltip Acetylcholinesterase	Inhibitors: Reversible: Carbamates: Aldicarb Aminocarb Bendiocarb Bufencarb Carbaryl Carbendazim Carbetamide Carbofuran Carbosulfan Chlorbufam Chloropropham Dimetilan Ethienocarb Ethiofencarb Fenobucarb Formetanate Formparanate Methiocarb Methomyl Metolcarb Miotine Oxamyl Phenmedipham Pinmicarb Pirimicarb Promecarb Propamocarb Propham Propoxur Thiodicarb Thiofanox; Stigmines: Distigmine Eptastigmine Ganstigmine Neostigmine +glycopyrronium bromide Phenserine Physostigmine Pyridostigmine Quilostigmine Rivastigmine Terestigmine; Others: Acotiamide Ambenonium Caffeine Donepezil EA-3990 EA-4056 Edrophonium Galantamine Huperzine A Huprine W Huprine X Huprine Y Ipidacrine Itopride Ladostigil Minaprine Octamethylene-bis(5-dimethylcarbamoxyisoquinolinium bromide) T-1123 T-1152 T-1194 TL-599 TL-1238 Tacrine Zanapezil Irreversible: Organophosphates: 2-Ethoxycarbonyl-1-methylvinyl cyclohexyl methylphosphonate Acephate Armine Azinphos-ethyl Azinphos-methyl BAY-29952 Bensulide Cadusafos Carbophenothion Chlorethoxyfos Chlorfenvinphos Chlorpyrifos Chlorpyrifos-methyl Coumaphos Crotylsarin Cyanophos Cyclosarin (GF) Demephion Demeton Demeton-S-methyl Dialifor Diazinon Dichlorvos Dicrotophos Dicyclohexyl phosphorofluoridate Diisopropylphosphate Diisopropyl fluorophosphate Dimefox Dimethoate Dimethyl 4-(methylthio)phenyl phosphate Dioxathion Disulfoton EA-2012 EA-2054 EA-2098 EA-2192 EA-2613 EA-3148 EA-4352 Echothiophate Ethylsarin (GE) Endothion EPN Ethion Ethoprop Fenamiphos Fenitrothion Fenthion Fluorotabun Fonofos Formothion Fosthiazate GD-42 GH GT-45 GV Guanitoxin Hexaethyl tetraphosphate (HETP) Isofluorophate Isoxathion Leptophos Malaoxon Malathion Mazidox Methamidophos Methidathion Methyl phenkapton Methylfluorophosphonylcholine (MFPCh) Metrifonate Mevinphos Mipafox Monocrotophos MSPI Naled Novichok agent Omethoate Oxydemeton-methyl Paraoxon Parathion Parathion-methyl Phorate Phosalone Phosfolan Phosmet Phosphamidon Phoxim Pirimiphos-methyl Profenofos Prothoate R-16661 Ro 3-0340 Ro 3-0346 Ro 3-0347 Ro 3-0351 Ro 3-0352 Ro 3-0397 Ro 3-0411 Ro 3-0412 Ro 3-0417 Ro 3-0419 Ro 3-0422 Ro 3-0433 Ronnel Sarin (GB) Schradan Soman (GD) Sulfotep (TEDP) Tabun (GA) Tebupirimfos Temefos Terbufos Tetrachlorvinphos Tetraethyl pyrophosphate (TEPP) Triazofos Tribufos Trichlorfon Trichloronate Tricresyl phosphate VE VG VM VP VS VR VX; Others: Demecarium Fasciculins (green mamba toxins) (1, 2, 3, 4) Onchidal (Onchidella binneyi) Methanesulfonyl fluoride Unsorted: α-Pinene α-Viniferin Affinine Affinisine Arisugacin A Bulbocapnine Conodurine Coronaridine Corydaline Corynoline Crimidine Cyclanoline Cymserine Harmaline Kobophenol A Lactucopicrin Lycorine Phosacetim Rosmarinic acid Stercuronium iodide Taspine Tetrahydrocannabinol Ungeremine Ungiminorine Dimethylcarbamoyl fluoride BW284C51 TMTFA 3152 CT Reactivators: Asoxime chloride Methoxime Obidoxime Pralidoxime Trimedoxime bromide
BChETooltip Butyrylcholinesterase	Inhibitors: Affinine Affinisine Conodurine Cymserine Ladostigil Profenamine (ethopropazine) Rivastigmine Tacrine ZINC-12613047 Many of the other AChE inhibitors listed above

Transporter
(modulators)

CHTTooltip Choline transporter	Inhibitors: Hemicholinium-3 (hemicholine) Triethylcholine Enhancers: Coluracetam
VAChTTooltip Vesicular acetylcholine transporter	Inhibitors: Vesamicol

Release
(modulators)

Inhibitors	SNAP-25Tooltip Synaptosomal-associated protein 25 inactivators: Botulinum toxin (A, C, E) VAMPTooltip Vesicle-associated membrane protein inactivators: Botulinum toxin (B, D, F, G) Others: Bungarotoxins (β-bungarotoxin, γ-bungarotoxin)
Enhancers	LPHNTooltip Latrophilin agonists: α-Latrotoxin Others: Atracotoxins (e.g., robustoxin, versutoxin) Crotoxin