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Identification
NameDiethylcarbamazine
Accession NumberDB00711  (APRD00918)
Typesmall molecule
Groupsapproved
Description

An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CarbamazineNot AvailableIS
DiethylcarbamazinGermanINN
DiéthylcarbamazineFrenchINN
DiethylcarbamazinumLatinINN
DietilcarbamazinaSpanishINN
Salts
Name/CAS Structure Properties
Diethylcarbamazine Citrate
Thumb Not applicable DBSALT000975
Brand names
NameCompany
BanocideGlaxoSmithKline
Banocide ForteGlaxoSmithKline
CarbilazineNot Available
CaricideNot Available
CypipNot Available
DecetRND Labs
DicarbInga
DiethizinePond's Chemical
EofilNot Available
EthodrylNot Available
HetrazanWyeth
NotezineSanofi-Aventis
SpatoninNot Available
SupatoninTanabe Mitsubishi Pharma
Brand mixtures
Brand NameIngredients
Cetrezol-DDiethylcarbamazine and Cetirizine
Cetrezol-D ForteDiethylcarbamazine and Cetirizine
Decet-BDDiethylcarbamazine and Cetirizine
Filaribits Plus 180/136mg Chewable TabletDiethylcarbamazine citrate + Oxibendazole
TrozanDiethylcarbamazine and Cetirizine
Categories
CAS number90-89-1
WeightAverage: 199.2932
Monoisotopic: 199.168462309
Chemical FormulaC10H21N3O
InChI KeyInChIKey=RCKMWOKWVGPNJF-UHFFFAOYSA-N
InChI
InChI=1S/C10H21N3O/c1-4-12(5-2)10(14)13-8-6-11(3)7-9-13/h4-9H2,1-3H3
IUPAC Name
N,N-diethyl-4-methylpiperazine-1-carboxamide
SMILES
CCN(CC)C(=O)N1CCN(C)CC1
Mass Specshow(11 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPiperazines
SubclassPiperazine Carboxylic Acids and Derivatives
Direct parentPiperazine Carboxamides
Alternative parentsDiazinanes; Tertiary Amines; Polyamines
Substituents1,4-diazinane; tertiary amine; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the piperazine carboxamides. These are heterocyclic compounds containing a piperazine ring substituted by one or more carboxamide group.
Pharmacology
IndicationUsed for the treatment of individual patients with certain filarial diseases including tropical pulmonary eosinophilia, loiasis, and lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori.
PharmacodynamicsDiethylcarbamazine is an anthelmintic drug that does not resemble other antiparasitic compounds. It is a synthetic organic compound which is highly specific for several parasites and does not contain any toxic metallic elements. Diethylcarbamazine continues to be the mainstay for treatment of patients with lymphatic filariasis and loiasis.
Mechanism of actionThe mechanism of action of diethylcarbamazine is thought to involve sensitizing the microfilariae to phagocytosis. One study showed that diethylcarbamazine's activity against Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway. It confirmed the important role of the arachidonic acid metabolic pathway in diethylcarbamazine's mechanism of action in vivo and showes that in addition to its effects on the 5-lipoxygenase pathway, it targets the cyclooxygenase pathway and COX-1.
AbsorptionReadily absorbed following oral administration.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Partially metabolized to diethylcarbamazine N-oxide.

SubstrateEnzymesProduct
Diethylcarbamazine
    diethylcarbamazine N-oxideDetails
    Route of eliminationNot Available
    Half lifeApproximately 8 hours.
    ClearanceNot Available
    ToxicityOral LD50 in rat and mouse is 1400 mg/kg and 660 mg/kg, respectively.
    Affected organisms
    • Humans and other mammals
    • Parasitic nematodes and other roundworms
    PathwaysNot Available
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9746
    Blood Brain Barrier + 0.9851
    Caco-2 permeable + 0.5947
    P-glycoprotein substrate Substrate 0.7326
    P-glycoprotein inhibitor I Non-inhibitor 0.6368
    P-glycoprotein inhibitor II Non-inhibitor 0.9745
    Renal organic cation transporter Non-inhibitor 0.6243
    CYP450 2C9 substrate Non-substrate 0.8563
    CYP450 2D6 substrate Non-substrate 0.9116
    CYP450 3A4 substrate Non-substrate 0.595
    CYP450 1A2 substrate Non-inhibitor 0.8168
    CYP450 2C9 substrate Non-inhibitor 0.882
    CYP450 2D6 substrate Non-inhibitor 0.8952
    CYP450 2C19 substrate Non-inhibitor 0.9141
    CYP450 3A4 substrate Non-inhibitor 0.9891
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9614
    Ames test Non AMES toxic 0.8203
    Carcinogenicity Non-carcinogens 0.9183
    Biodegradation Not ready biodegradable 0.85
    Rat acute toxicity 2.2639 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.5
    hERG inhibition (predictor II) Non-inhibitor 0.7766
    Pharmacoeconomics
    Manufacturers
    • Lederle laboratories div american cyanamid co
    PackagersNot Available
    Dosage formsNot Available
    PricesNot Available
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point48 °CPhysProp
    water solubility63.7 mg/mL at 25 °CMEYLAN,WM et al. (1996)
    logP0.1Not Available
    Predicted Properties
    PropertyValueSource
    water solubility2.36e+02 g/lALOGPS
    logP0.9ALOGPS
    logP0.092ChemAxon
    logS0.07ALOGPS
    pKa (strongest basic)6.9ChemAxon
    physiological charge0ChemAxon
    hydrogen acceptor count2ChemAxon
    hydrogen donor count0ChemAxon
    polar surface area26.79ChemAxon
    rotatable bond count2ChemAxon
    refractivity58.28ChemAxon
    polarizability22.89ChemAxon
    number of rings1ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleYesChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis ReferenceNot Available
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG DrugD00803
    KEGG CompoundC07968
    PubChem Compound3052
    PubChem Substance46506830
    ChemSpider2944
    BindingDB50024883
    Therapeutic Targets DatabaseDAP000914
    PharmGKBPA164748883
    Drug Product Database346667
    WikipediaDiethylcarbamazine
    ATC CodesP02CB02
    AHFS CodesNot Available
    PDB EntriesNot Available
    FDA labelNot Available
    MSDSshow(65.5 KB)
    Interactions
    Drug InteractionsNot Available
    Food InteractionsNot Available

    1. Arachidonate 5-lipoxygenase

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Arachidonate 5-lipoxygenase P09917 Details

    References:

    1. Bach MK, Brashler JR: Inhibition of the leukotriene synthetase of rat basophil leukemia cells by diethylcarbamazine, and synergism between diethylcarbamazine and piriprost, a 5-lipoxygenase inhibitor. Biochem Pharmacol. 1986 Feb 1;35(3):425-33. Pubmed
    2. Cernak I, Savic J, Malicevic Z, Zunic G, Radosevic P, Ivanovic I: Leukotrienes in the pathogenesis of pulmonary blast injury. J Trauma. 1996 Mar;40(3 Suppl):S148-51. Pubmed
    3. Gross NJ, Holloway NO, Narine KR: Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis. Radiat Res. 1991 Sep;127(3):317-24. Pubmed
    4. Zunic G, Cernak I, Malicevic Z, Savic J: Inhibition of leukotriene formation by diethylcarbamazine modifies the acid-base balance in the rabbits with blast injuries of the lungs. Vojnosanit Pregl. 1999 May-Jun;56(3):243-7. Pubmed
    5. Davidson D, Drafta D: Prolonged pulmonary hypertension caused by platelet-activating factor and leukotriene C4 in the rat lung. J Appl Physiol. 1992 Sep;73(3):955-61. Pubmed
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

    2. Prostaglandin G/H synthase 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Prostaglandin G/H synthase 1 P23219 Details

    References:

    1. McGarry HF, Plant LD, Taylor MJ: Diethylcarbamazine activity against Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway. Filaria J. 2005 Jun 2;4:4. Pubmed

    1. Cholinesterase

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cholinesterase P06276 Details

    References:

    1. Fujimaki Y, Sakamoto M, Shimada M, Kimura E, Aoki Y: Diethylcarbamazine: inhibitory effect on acetylcholinesterase of Dirofilaria immitis and Brugia pahangi. Southeast Asian J Trop Med Public Health. 1989 Jun;20(2):179-82. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11