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Record Information
Version2.0
Creation Date2013-04-25 07:56:53 UTC
Update Date2014-12-24 20:26:33 UTC
Accession NumberT3D3878
Identification
Common Name(±)-Methamidophos
ClassSmall Molecule
DescriptionMethamidophos is a highly active, systemic, residual organophosphate insecticide/acaricide/avicide with contact and stomach action. Its mode of action in insects and mammals is through inhibition of acetylcholinesterase. This enzyme is essential in the normal transmission of nerve impulses. Methamidophos is a potent acetylcholinesterase inhibitor. It is particularly effective against chewing and sucking insects and is used to control aphids, flea beetles, worms, whiteflies, thrips, cabbage loopers, Colorado potato beetles, potato tubeworms, armyworms, mites, leafhoppers, and many others. Crop uses include broccoli, Brussel sprouts, cauliflower, grapes, celery, sugar beets, cotton, tobacco, and potatoes. It is used abroad for many vegetables, hops, corn, peaches, and other crops Due to its toxicity, the use of pesticides that contain methamidophos is currently being phased out in Brazil. Methamidophos is highly toxic via oral, dermal and inhalation routes of exposure. Methamidophos was found in dumplings (gyoza) manufactured in China for the Japanese market after a number of consumers became sick.
Compound Type
  • Amide
  • Food Toxin
  • Insecticide
  • Metabolite
  • Organic Compound
  • Organophosphate
  • Pesticide
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(±)-methamidophos
Acephate-met
Amidor
Chevron 9006
Chevron ortho 9006
Filitox
Hamidop
Metamidofos estrella
Metamidophos
Methamidophos
Methyl phosphoramidothioate
Methyl phosphoramidothioate ((MeO)(MeS)P(O)(NH2))
Monitor
Monitor (insecticide)
MTD
O,S-Dimethyl amidothiophosphate
O,S-Dimethyl phosphoramidothioate
O,S-Dimethyl phosphoramidothiolate
O,S-Dimethyl phosphoroamidothioate
O,S-Dimethylphosphoroamidothioate
Ortho monitor
Patrole
Phosphoramidothioic acid, O,S-dimethyl ester
Pillaron
Sniper
Tahmabon
Tamanox
Tamaron
Chemical FormulaC2H8NO2PS
Average Molecular Mass141.129 g/mol
Monoisotopic Mass141.001 g/mol
CAS Registry Number115182-35-9
IUPAC Name[methoxy(methylsulfanyl)phosphoryl]amine
Traditional Nametamaron
SMILESCOP(N)(=O)SC
InChI IdentifierInChI=1/C2H8NO2PS/c1-5-6(3,4)7-2/h1-2H3,(H2,3,4)
InChI KeyInChIKey=NNKVPIKMPCQWCG-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phosphoramidothioic-acid-o,s-diesters. These are organooxygen compounds containing a O,S-diester derivative of phosphoroamidothioic acid. They have the general structure RSP(=O)(OR')(NH2), where R,R' are organyl groups.
KingdomOrganic compounds
Super ClassOrganophosphorus compounds
ClassOrganothiophosphorus compounds
Sub ClassPhosphoramidothioic-acid-O,S-diesters
Direct ParentPhosphoramidothioic-acid-O,S-diesters
Alternative Parents
Substituents
  • Phosphoramidothioic-acid-o,s-diester
  • Sulfenyl compound
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility30.6 g/LALOGPS
logP-0.94ALOGPS
logP-0.32ChemAxon
logS-0.66ALOGPS
pKa (Strongest Acidic)15.57ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.32 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity31.68 m³·mol⁻¹ChemAxon
Polarizability12.07 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-08i4-9300000000-56d4e3bc363cce753683JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0007-7900000000-32e474674de8c15ed60aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0005-9300000000-b1c907e2fd5c6190ef90JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01ot-9000000000-19efb41eb42da7683de1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000f-9700000000-bc4a47915aa2f2d4402fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-9000000000-d2352d752bc864cb342cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4j-9500000000-66b182cec233c6816900JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of Toxicity(±)-Methamidophos is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismMetabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsSymptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB31803
PubChem Compound ID4096
ChEMBL IDNot Available
ChemSpider ID3954
KEGG IDC18667
UniProt IDNot Available
OMIM ID
ChEBI ID38721
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D3878.pdf
General References
  1. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
References
  1. Tacal O, Lockridge O: Methamidophos, dichlorvos, O-methoate and diazinon pesticides used in Turkey make a covalent bond with butyrylcholinesterase detected by mass spectrometry. J Appl Toxicol. 2010 Jul;30(5):469-75. doi: 10.1002/jat.1518. [20229498 ]
General Function:
Urokinase plasminogen activator receptor activity
Specific Function:
Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
Gene Name:
PLAUR
Uniprot ID:
Q03405
Molecular Weight:
36977.62 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.48 uMBSK_BE3C_uPAR_upBioSeek
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]