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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
SynonymLanguageCode
[(Dimethoxyphosphinothioyl)thio]butanedioic acid diethyl esterNot AvailableNot Available
CarbophosNot AvailableNot Available
Diethyl (dimethoxyphosphinothioylthio)succinateNot AvailableNot Available
KarbofosNot AvailableNot Available
MalathionNot AvailableNot Available
MaldisonNot AvailableNot Available
MercaptothionNot AvailableNot Available
O,O-Dimethyl S-(1,2-bis(ethoxycarbonyl)ethyl)Not AvailableNot Available
O,O-Dimethyl S-(1,2-dicarbethoxyethyl) dithiophosphateNot AvailableNot Available
O,O-Dimethyl S-(1,2-dicarbethoxyethyl)phosphorodithioateNot AvailableNot Available
O,O-Dimethyl S-1,2-di(ethoxycarbamyl)ethylNot AvailableNot Available
O,O-Dimethyldithiophosphate diethylmercaptosuccinateNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
Derbac-MSSL
NouryAlfaco
OvideTaro
PriodermNorpharma
Brand mixturesNot Available
Categories
CAS number121-75-5
WeightAverage: 330.358
Monoisotopic: 330.036066232
Chemical FormulaC10H19O6PS2
InChI KeyJXSJBGJIGXNWCI-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
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
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 Solubility0.165ALOGPS
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra1D NMR
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

Targets

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

Enzymes

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

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Drug created on June 13, 2005 07:24 / Updated on May 23, 2014 10:56