You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
Di├ęthylcarbamazineFrenchINN
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 KeyRCKMWOKWVGPNJF-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
Not Available
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 point150-155Kushner, S. and Brancone, L.; US. Patent 2,467,893; April 19,1949; assigned to American Cyanamid Company. Kushner, S. and Brancone, L.; US. Patent 2,467,895; April 19, 1949; assigned to American Cyanamid Company.
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 Reference

Kushner, S. and Brancone, L.; US. Patent 2,467,893; April 19,1949; assigned to American
Cyanamid Company.
Kushner, S. and Brancone, L.; US. Patent 2,467,895; April 19, 1949; assigned to American
Cyanamid Company.

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

Targets

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

Enzymes

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
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on April 14, 2014 10:28