METRIFONATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C4H8Cl3O4P
Molecular Weight	257.437
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=NFACJZMKEDPNKN-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C4H8Cl3O4P
Molecular Weight	257.437
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://apps.who.int/medicinedocs/en/d/Jh2922e/3.7.2.html
Curator's Comment: Description was created based on several sources including http://pmep.cce.cornell.edu/profiles/extoxnet/pyrethrins-ziram/trichlorfon-ext.html and http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.1999.tb00083.x/pdf

Trichlorfon (Metrifonate), the organophosphorous cholinesterase inhibitor, O,O-dimethylhydroxy-2,2,2-trichlorethyl-phosphonate, has been used sporadically in the treatment of human schistosomiasis for a decade. It has selective and variable schistosomicidal activity against S. haematobium that results from its partial metabolism to a highly active anti-cholinesterase, dichlorvos. Schistosomal cholinesterase is more susceptible to this metabolite than that of the human host, but transient reductions in both plasma and erythrocyte cholinesterase activity are demonstrable at therapeutic dosage. However, despite early concerns about its potential toxicity, metrifonate is well tolerated and has been used effectively and extensively in large-scale control programmes. Its potential to enhance central nervous system cholinergic neurotransmission led to clinical trials for the treatment of people with Alzheimer's disease (AD).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acetylcholinesterase 209 Target ID: CHEMBL3199 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11311445	Inhibitor 8504	1.44 µM [IC50]
Butyrylcholinesterase 45 Target ID: CHEMBL3403 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11311445	Inhibitor 8504	0.22 µM [IC50]
Acetylcholinesterase 209 Target ID: CHEMBL220 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12794390	Inhibitor 8504	525.0 µM [Ki]
Butyrylcholinesterase 45 Target ID: CHEMBL1914 Sources: http://www.ncbi.nlm.nih.gov/pubmed/12794390	Inhibitor 8504	36.7 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary schistosomiasis 3 Sources: http://apps.who.int/medicinedocs/en/d/Jh2922e/3.7.2.html	Curative		Withdrawn	Unknown Approved Use Unknown
Alzheimer’s disease 278 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16625573	Primary		Withdrawn	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Activity profiles of 309 ToxCast™ chemicals evaluated across 292 biochemical targets.	2011-03-28	21251949
Why so few drugs for Alzheimer's disease? Are methods failing drugs?	2010-11	20704560
Expression characteristics of potential biomarker genes in Tra catfish, Pangasianodon hypophthalmus, exposed to trichlorfon.	2010-09	20570226
Acetylcholinesterase biosensor based on Prussian blue-modified electrode for detecting organophosphorous pesticides.	2010-08-15	20466535
Impact of hookworm infection and deworming on anaemia in non-pregnant populations: a systematic review.	2010-07	20500563
Concurrent helminthic infection protects schoolchildren with Plasmodium vivax from anemia.	2010-06-21	20574512
Efficacy study of Prunus amygdalus (almond) nuts in scopolamine-induced amnesia in rats.	2010-06	20871769
Luminescent Mycena: new and noteworthy species.	2010-04-06	20361513
Immunohistological studies on neoplasms of female and male Onchocerca volvulus: filarial origin and absence of Wolbachia from tumor cells.	2010-04	20199697
Impact of environmental chemicals on key transcription regulators and correlation to toxicity end points within EPA's ToxCast program.	2010-03-15	20143881
Mass spectrometric analyses of organophosphate insecticide oxon protein adducts.	2010-01	20056576
Tunga penetrans: painful lesions on the feet-the first imported case from Guinea-bissau.	2010	21209743
Enzyme Inhibition by Molluscicidal Components of Myristica fragrans Houtt. in the Nervous Tissue of Snail Lymnaea acuminata.	2010	21048864
Treatment of urinary schistosomiasis: methodological issues and research needs identified through a Cochrane systematic review.	2009-11	19493363
Ultrasonographic screening of urinary schistosomiasis infected patients in Agulu community, Anambra state, southeast Nigeria.	2009-10-28	19863804
Trichlorfon induces apoptosis in SH-SY5Y neuroblastoma cells via the endoplasmic reticulum?	2009-09-14	19631781
In vitro reactivation of trichlorfon-inhibited butyrylcholinesterase using HI-6, obidoxime, pralidoxime and K048.	2009-06	18825528
Do antenatal parasite infections devalue childhood vaccination?	2009-05-26	19478847
In vivo 1H-magnetic resonance spectroscopy can detect metabolic changes in APP/PS1 mice after donepezil treatment.	2009-04-07	19351388
Have last-observation-carried-forward analyses caused us to favour more toxic dementia therapies over less toxic alternatives? A systematic review.	2009-03-24	19946392
Longitudinal multimodal imaging in mild to moderate Alzheimer disease: a pilot study with memantine.	2008-12	18586865
Improvement of acetylcholinesterase-based assay for organophosphates in way of identification by reactivators.	2008-10-19	18804659
Prize sessions.	2008-10	21593975
The effects of rivastigmine plus selegiline on brain acetylcholinesterase, (Na, K)-, Mg-ATPase activities, antioxidant status, and learning performance of aged rats.	2008-08	19043511
Drugs for treating urinary schistosomiasis.	2008-07-16	18646057
Effect of intermittent preventive treatment of malaria on health and education in schoolchildren: a cluster-randomised, double-blind, placebo-controlled trial.	2008-07-12	18620950
The synergistic effect of concomitant schistosomiasis, hookworm, and trichuris infections on children's anemia burden.	2008-06-04	18523547
Controlling schistosomiasis: significant decrease of anaemia prevalence one year after a single dose of praziquantel in Nigerian schoolchildren.	2008-05-28	18509472
Incident diabetes and pesticide exposure among licensed pesticide applicators: Agricultural Health Study, 1993-2003.	2008-05-15	18343878
Pharmacodynamics of memantine: an update.	2008-03	19305788
Effect of glabridin from Glycyrrhiza glabra on learning and memory in mice.	2008-03	18484526
Lysophospholipase from the human blood fluke, Schistosoma japonicum.	2008-03	17709268
Impact of cholinesterase inhibitors on behavioral and psychological symptoms of Alzheimer's disease: a meta-analysis.	2008	19281064
A comparative study on the relationship between various toxicological endpoints in Caenorhabditis elegans exposed to organophosphorus insecticides.	2008	18569613
Noncholinesterase effects induced by organophosphate pesticides and their relationship to cognitive processes: implication for the action of acylpeptide hydrolase.	2007-12	18049927
Effects of trichlorfon on malondialdehyde and antioxidant system in human erythrocytes.	2007-12	17697763
[Different therapeutic efficacy of pralidoxime chloride PAM-Cl on AChE against acute toxicity of methamidophos, dichlorvos and omethoate].	2007-10	18070496
The effect of trichlorfon on acetylcholinesterase activity and histopathology of cultivated fish Oreochromis niloticus.	2007-09	17055053
Effects of trichlorfon on progesterone production in cultured human granulosa-lutein cells.	2007-08	17329077
Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics.	2007-06	19300564
The PDE4 inhibitor rolipram reverses object memory impairment induced by acute tryptophan depletion in the rat.	2007-06	17265077
Study on the mechanism of trichlorfon-induced inhibition of progesterone synthesis in mouse leydig tumor cells (MLTC-1).	2007-05-05	17350742
Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor.	2007-01	17214506
Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth muscles.	2006-11	17218977
Response from Savioli and colleagues from the Department of Neglected Tropical Diseases, World Health Organization.	2006-06	16789805
Metrifonate for Alzheimer's disease.	2006-04-19	16625573
Neuropsychiatric symptoms as a predictor of caregiver burden in Alzheimer's disease.	2006-03	19412452
Comparative brain cholinesterase-inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid, and metrifonate in mice.	2006	16822217
Inhibition-based determination of metrifonate in liquid and solid samples using the triple integration chemical hydrolysis-pervaporation-enzymic derivatisation.	2001-01-26	18968186
Pharmacokinetics of metrifonate and its rearrangement product dichlorvos in whole blood.	1991-02	1852719

Patents

Sample Use Guides

In Vivo Use Guide

Treatment of urinary schistosomiasis: Adults and children: a dose of 7.5-10 mg/kg on three occasions at intervals of 2 weeks will cure 40-80% of cases. Even when viable worms remain, egg counts after one year are reduced to less than 20% of pre-treatment levels.

Route of Administration: Oral

In Vitro Use Guide

100 ug/ml trichlorfon added at the time of hormonally stimulated resumption of meiosis of follicle cell-enclosed mouse oocytes, 16 h before in vitro ovulation, induced significant rises in first meiotic nondisjunction in oocytes from preantral follicle culture.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 19:21:09 GMT 2025` Edited by `admin` on `Mon Mar 31 19:21:09 GMT 2025`
Record UNII	DBF2DG4G2K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRICHLORFON

Preferred Name

English

METRIFONATE

Official Name

English

DETF

Common Name

English

METRIFONATE [MART.]

Common Name

English

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

Systematic Name

English

METRIFONATE [USP MONOGRAPH]

Common Name

English

TRICHLORFON [IARC]

Common Name

English

TRICHLORFON [USP-RS]

Common Name

English

DIMETHYL (RS)-2,2,2-TRICHLORO-1-HYDROXYETHYLPHOSPHONATE

Systematic Name

English

DIMETHYL (P)-(2,2,2-TRICHLORO-1-HYDROXYETHYL)PHOSPHONATE

Common Name

English

METRIPHONATE

Common Name

English

BAYER-L-1359

Code

English

WEC-50

Code

English

METRIFONATUM [WHO-IP LATIN]

Common Name

English

TRICHLOROFON

Brand Name

English

METRIFONATE [EP IMPURITY]

Common Name

English

TRICLORFON

Common Name

English

METRIFONATE [WHO-IP]

Common Name

English

TRICHLORFON [HSDB]

Common Name

English

BAY-A 9826

Code

English

TRICHLORFON [USAN]

Common Name

English

TRICHLORFON [ISO]

Common Name

English

ENT-19,763

Code

English

metrifonate [INN]

Common Name

English

PHOSPHONIC ACID, (2,2,2-TRICHLORO-1-HYDROXYETHYL)-, DIMETHYL ESTER

Systematic Name

English

Metrifonate [WHO-DD]

Common Name

English

NSC-8923

Code

English

TRICHLORFON [GREEN BOOK]

Common Name

English

TRICHLORFON [MI]

Common Name

English

METRIFONATE [USP IMPURITY]

Common Name

English

BAYER L 1359

Code

English

Classification Tree Code System Code

CFR

21 CFR 520.2520