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Identification
NameMalathion
Accession NumberDB00772  (APRD01081)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Malathion is a parasympathomimetic organophosphate compound that is used as an insecticide for the treatment of head lice. Malathion is an irreversible cholinesterase inhibitor and has low human toxicity.

Structure
Thumb
Synonyms
[(Dimethoxyphosphinothioyl)thio]butanedioic acid diethyl ester
Carbophos
Diethyl (dimethoxyphosphinothioylthio)succinate
Karbofos
Malathion
Maldison
Mercaptothion
O,O-Dimethyl S-(1,2-bis(ethoxycarbonyl)ethyl)
O,O-Dimethyl S-(1,2-dicarbethoxyethyl) dithiophosphate
O,O-Dimethyl S-(1,2-dicarbethoxyethyl)phosphorodithioate
O,O-Dimethyl S-1,2-di(ethoxycarbamyl)ethyl
O,O-Dimethyldithiophosphate diethylmercaptosuccinate
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Malathionlotion.005 g/mLtopicalTaro Pharmaceuticals U.S.A., Inc.2009-08-02Not applicableUs
Ovidelotion.005 g/mLtopicalTARO PHARMACEUTICALS USA, INC.1982-08-02Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Malathionlotion.005 g/mLtopicalSuven Life Sciences Limited2014-02-20Not applicableUs
Malathionlotion.0005 g/mLtopicalTaro Pharmaceuticals U.S.A., Inc.2014-01-31Not applicableUs
Malathion Lotion, 0.5%lotion5 mg/mLtopicalKaralex Pharma, Llc, Woodcliff Lake, Nj 076772009-05-13Not applicableUs
Ovidelotion.0005 g/mLtopicalTaro Pharmaceuticals U.S.A., Inc.2014-01-31Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Derbac-MSSL
NouryAlfaco
PriodermNorpharma
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIU5N7SU872W
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)-λ⁵-phosphanyl]sulfanyl}butanedioate
SMILES
CCOC(=O)CC(SP(=S)(OC)OC)C(=O)OCC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as fatty acid esters. These are carboxylic ester derivatives of a fatty acid.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acid esters
Direct ParentFatty acid esters
Alternative Parents
Substituents
  • Fatty acid ester
  • Dithiophosphate s-ester
  • Dithiophosphate ester
  • Dicarboxylic acid or derivatives
  • Organic dithiophosphate
  • Carboxylic acid ester
  • Sulfenyl compound
  • Organothiophosphorus compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
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.
Related Articles
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
Not Available
MalaoxonDetails
Malathion
Not Available
Malathion dicarboxylic acidDetails
Malathion
Not Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9031
Blood Brain Barrier+0.9236
Caco-2 permeable-0.5579
P-glycoprotein substrateNon-substrate0.7901
P-glycoprotein inhibitor INon-inhibitor0.6817
P-glycoprotein inhibitor IINon-inhibitor0.9522
Renal organic cation transporterNon-inhibitor0.9414
CYP450 2C9 substrateNon-substrate0.8308
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.6132
CYP450 1A2 substrateNon-inhibitor0.8415
CYP450 2C9 inhibitorNon-inhibitor0.7963
CYP450 2D6 inhibitorNon-inhibitor0.9114
CYP450 2C19 inhibitorNon-inhibitor0.748
CYP450 3A4 inhibitorNon-inhibitor0.5673
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8504
Ames testNon AMES toxic0.9132
CarcinogenicityCarcinogens 0.6261
BiodegradationNot ready biodegradable0.8429
Rat acute toxicity3.0259 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9228
hERG inhibition (predictor II)Non-inhibitor0.8641
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Synerx pharma llc
  • Taro pharmaceuticals north america inc
Packagers
Dosage forms
FormRouteStrength
Lotiontopical5 mg/mL
Lotiontopical.0005 g/mL
Lotiontopical.005 g/mL
Prices
Unit descriptionCostUnit
Ovide 0.5% Lotion 59ml Bottle180.8USD bottle
Ovide 0.5% lotion2.95USD ml
Malathion 0.5% lotion2.65USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7560445 No2007-02-012027-02-01Us
US7977324 No2006-08-142026-08-14Us
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 Solubility0.165 mg/mLALOGPS
logP2.67ALOGPS
logP1.86ChemAxon
logS-3.3ALOGPS
pKa (Strongest Basic)-6.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area71.06 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity78.18 m3·mol-1ChemAxon
Polarizability31.66 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (10.5 KB)
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-004i-8900000000-c6bc16fae6e217410d40View in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
References
Synthesis Reference

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

US4367180
General References
  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:74508 ]
  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:17720683 ]
  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:16914134 ]
External Links
ATC CodesP03AX03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (133 KB)
MSDSDownload (57.9 KB)
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  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:17016423 ]
  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:16782587 ]
  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:17364237 ]
  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:16716398 ]
  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:10592235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on July 27, 2016 01:55