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Identification
NameMalathion
Accession NumberDB00772  (APRD01081)
Typesmall molecule
Groupsapproved, investigational
Description

A wide spectrum aliphatic organophosphate insecticide widely used for both domestic and commercial agricultural purposes. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CarbophosNot AvailableNot Available
MaldisonNot AvailableNot Available
MercaptothionNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Derbac-MNot Available
OvideNot Available
PriodermNot Available
Quellada-MNot Available
Brand mixturesNot Available
Categories
CAS number121-75-5
WeightAverage: 330.358
Monoisotopic: 330.036066232
Chemical FormulaC10H19O6PS2
InChI KeyInChIKey=JXSJBGJIGXNWCI-UHFFFAOYSA-N
InChI
InChI=1S/C10H19O6PS2/c1-5-15-9(11)7-8(10(12)16-6-2)19-17(18,13-3)14-4/h8H,5-7H2,1-4H3
IUPAC Name
1,4-diethyl 2-{[dimethoxy(sulfanylidene)-$l^{5}-phosphanyl]sulfanyl}butanedioate
SMILES
CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC
Mass Specshow(10.5 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassDicarboxylic Acids and Derivatives
Direct parentDicarboxylic Acids and Derivatives
Alternative parentsFatty Acid Esters; Organic Phosphonic Acids and Derivatives; Carboxylic Acid Esters; Organothiophosphorus Compounds; Ethers; Enolates; Polyamines
Substituentsphosphonic acid derivative; carboxylic acid ester; organothiophosphorus compound; polyamine; ether; enolate
Classification descriptionThis compound belongs to the dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.
Pharmacology
IndicationFor patients infected with Pediculus humanus capitis (head lice and their ova) of the scalp hair.
PharmacodynamicsMalathion is an organophosphate insecticide commonly used to control mosquitos and other flying insects. Pharmaceutically, malathion is used to eliminate head lice. The principal toxicological effect of malathion is cholinesterase inhibition, due primarily to malaoxon and to phosphorus thionate impurities.
Mechanism of actionMalathion is a nonsystemic, wide-spectrum organophosphate insecticide. It inhibits acetylcholinesterase activity of most eukaryotes. Malathion is toxic to aquatic organisms, but has a relatively low toxicity for birds and mammals. The major metabolites of malathion are mono- and di-carboxylic acid derivatives, and malaoxon is a minor metabolite. However, it is malaoxon that is the strongest cholinesterase inhibitor. Cholinesterases catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation. Because of its essential function, chemicals that interfere with the action of cholinesterase are potent neurotoxins, causing muscle spasms and ultimately death.
AbsorptionMalathion in an acetone vehicle has been reported to be absorbed through normal human skin only to the extent of 8% of the applied dose. Absorption may be increased when malathion is applied to damaged skin. Malathion is rapidly and effectively absorbed by practically all routes including the gastrointestinal tract, skin, mucous membranes, and lungs. However, it is readily excreted in the urine, and does not accumulate in organs or tissues.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

The major metabolites of malathion are the diacid and monoacid metabolites, namely, malathion dicarboxylic acid (DCA) and malathion monocarboxylic acid (MCA). Malaoxon, the active cholinesterase-inhibiting metabolite of malathion, is a minor metabolite. Both malathion and malaoxon are detoxified by carboxyesterases leading to polar, water-soluble compounds that are excreted.

SubstrateEnzymesProduct
Malathion
    MalaoxonDetails
    Malathion
      Malathion dicarboxylic acidDetails
      Malathion
        Malathion monocarboxylic acidDetails
        Route of eliminationNot Available
        Half life8-24 hours
        ClearanceNot Available
        ToxicityMalathion is slightly toxic via the oral route, with reported oral LD50 values of 1000 mg/kg to greater than 10,000 mg/kg in the rat. It is also slightly toxic via the dermal route, with reported dermal LD50 values of greater than 4000 mg/kg in rats. Moderate poisoning can result in chest tightness, difficulty breathing, bradycardia, tachycardia, tremor/ataxia, blurred vision, and confusion. Severe, life-threatening signs include coma, seizures, respiratory arrest, and paralysis. Malathion may also be irritating to the skin and eyes.
        Affected organisms
        • Head lice
        PathwaysNot Available
        SNP Mediated EffectsNot Available
        SNP Mediated Adverse Drug ReactionsNot Available
        ADMET
        Predicted ADMET features
        Property Value Probability
        Human Intestinal Absorption + 0.9031
        Blood Brain Barrier + 0.9236
        Caco-2 permeable - 0.5579
        P-glycoprotein substrate Non-substrate 0.7901
        P-glycoprotein inhibitor I Non-inhibitor 0.6817
        P-glycoprotein inhibitor II Non-inhibitor 0.9522
        Renal organic cation transporter Non-inhibitor 0.9414
        CYP450 2C9 substrate Non-substrate 0.8308
        CYP450 2D6 substrate Non-substrate 0.9116
        CYP450 3A4 substrate Non-substrate 0.6132
        CYP450 1A2 substrate Non-inhibitor 0.8415
        CYP450 2C9 substrate Non-inhibitor 0.7963
        CYP450 2D6 substrate Non-inhibitor 0.9114
        CYP450 2C19 substrate Non-inhibitor 0.748
        CYP450 3A4 substrate Non-inhibitor 0.5673
        CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8504
        Ames test Non AMES toxic 0.9132
        Carcinogenicity Carcinogens 0.6261
        Biodegradation Not ready biodegradable 0.8429
        Rat acute toxicity 3.0259 LD50, mol/kg Not applicable
        hERG inhibition (predictor I) Weak inhibitor 0.9228
        hERG inhibition (predictor II) Non-inhibitor 0.8641
        Pharmacoeconomics
        Manufacturers
        • Synerx pharma llc
        • Taro pharmaceuticals north america inc
        Packagers
        Dosage forms
        FormRouteStrength
        LotionTopical
        Prices
        Unit descriptionCostUnit
        Ovide 0.5% Lotion 59ml Bottle180.8USDbottle
        Ovide 0.5% lotion2.95USDml
        Malathion 0.5% lotion2.65USDml
        DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
        Patents
        CountryPatent NumberApprovedExpires (estimated)
        United States75604452007-02-012027-02-01
        Properties
        Stateliquid
        Experimental Properties
        PropertyValueSource
        melting point2.8 °CPhysProp
        boiling point156-157 °C at 7.00E-01 mm HgPhysProp
        water solubility143 mg/L (at 20 °C)BOWMAN,BT & SANS,WW (1983)
        logP2.36HANSCH,C ET AL. (1995)
        Predicted Properties
        PropertyValueSource
        water solubility1.65e-01 g/lALOGPS
        logP2.67ALOGPS
        logP1.86ChemAxon
        logS-3.3ALOGPS
        pKa (strongest basic)-6.8ChemAxon
        physiological charge0ChemAxon
        hydrogen acceptor count2ChemAxon
        hydrogen donor count0ChemAxon
        polar surface area71.06ChemAxon
        rotatable bond count11ChemAxon
        refractivity78.18ChemAxon
        polarizability31.66ChemAxon
        number of rings0ChemAxon
        bioavailability1ChemAxon
        rule of fiveYesChemAxon
        Ghose filterYesChemAxon
        Veber's ruleNoChemAxon
        MDDR-like ruleNoChemAxon
        Spectra
        SpectraNot Available
        References
        Synthesis Reference

        Noel Rouy, Georges Gros, “Process for the preparation of malathion.” U.S. Patent US4367180, issued August, 1969.

        US4367180
        General Reference
        1. Baker EL Jr, Warren M, Zack M, Dobbin RD, Miles JW, Miller S, Alderman L, Teeters WR: Epidemic malathion poisoning in Pakistan malaria workers. Lancet. 1978 Jan 7;1(8054):31-4. Pubmed
        2. Bonner MR, Coble J, Blair A, Beane Freeman LE, Hoppin JA, Sandler DP, Alavanja MC: Malathion exposure and the incidence of cancer in the agricultural health study. Am J Epidemiol. 2007 Nov 1;166(9):1023-34. Epub 2007 Aug 23. Pubmed
        3. Edwards JW, Lee SG, Heath LM, Pisaniello DL: Worker exposure and a risk assessment of malathion and fenthion used in the control of Mediterranean fruit fly in South Australia. Environ Res. 2007 Jan;103(1):38-45. Epub 2006 Aug 17. Pubmed
        External Links
        ResourceLink
        KEGG DrugD00534
        KEGG CompoundC07497
        PubChem Compound4004
        PubChem Substance46505287
        ChemSpider3864
        BindingDB50240924
        ChEBI6651
        ChEMBLCHEMBL1200468
        Therapeutic Targets DatabaseDAP000895
        PharmGKBPA164748092
        RxListhttp://www.rxlist.com/cgi/generic3/ovide.htm
        Drugs.comhttp://www.drugs.com/cdi/malathion.html
        WikipediaMalathion
        ATC CodesP03AX03
        AHFS CodesNot Available
        PDB EntriesNot Available
        FDA labelshow(133 KB)
        MSDSshow(57.9 KB)
        Interactions
        Drug InteractionsSearched, but no interactions found.
        Food InteractionsNot Available

        1. Cholinesterase

        Kind: protein

        Organism: Human

        Pharmacological action: yes

        Actions: inhibitor

        Components

        Name UniProt ID Details
        Cholinesterase P06276 Details

        References:

        1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
        2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
        3. Ramos ZR, Fortunato JJ, Agostinho FR, Martins MR, Correa M, Schetinger MR, Dal-Pizzol F, Quevedo J: Influence of malathion on acetylcholinesterase activity in rats submitted to a forced swimming test. Neurotox Res. 2006 Jun;9(4):285-90. Pubmed
        4. Ahmed M, Rocha JB, Mazzanti CM, Morsch AL, Cargnelutti D, Correa M, Loro V, Morsch VM, Schetinger MR: Malathion, carbofuran and paraquat inhibit Bungarus sindanus (krait) venom acetylcholinesterase and human serum butyrylcholinesterase in vitro. Ecotoxicology. 2007 May;16(4):363-9. Epub 2007 Mar 16. Pubmed
        5. da Silva AP, Meotti FC, Santos AR, Farina M: Lactational exposure to malathion inhibits brain acetylcholinesterase in mice. Neurotoxicology. 2006 Dec;27(6):1101-5. Epub 2006 Apr 28. Pubmed
        6. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

        1. Cytochrome P450 1A2

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 1A2 P05177 Details

        References:

        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        2. Cytochrome P450 2B6

        Kind: protein

        Organism: Human

        Pharmacological action: unknown

        Actions: substrate

        Components

        Name UniProt ID Details
        Cytochrome P450 2B6 P20813 Details

        References:

        1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

        Comments
        Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12