Identification
NameDiethylcarbamazine
Accession NumberDB00711  (APRD00918)
TypeSmall Molecule
GroupsApproved, Vet Approved
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
Camin
Carbamazine
Diethylcarbamazin
Diéthylcarbamazine
Diethylcarbamazinum
Dietilcarbamazina
N,N-Diethyl-4-methyl-1-piperazinecarboxamide
External IDs L 84 / RP 3799
Product Ingredients
IngredientUNIICASInChI KeyDetails
Diethylcarbamazine CitrateOS1Z389K8S 1642-54-2PGNKBEARDDELNB-UHFFFAOYSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hetrazan Tab 50mgTablet50 mgOralLederle Cyanamid Canada Inc.1982-05-312000-08-02Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
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 mixturesNot Available
Categories
UNIIV867Q8X3ZD
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
Pharmacology
Indication

Used 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.

Structured Indications Not Available
Pharmacodynamics

Diethylcarbamazine 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 action

The 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
Arachidonate 5-lipoxygenaseProteinyes
inhibitor
HumanP09917 details
Prostaglandin G/H synthase 1Proteinunknown
inhibitor
HumanP23219 details
Related Articles
Absorption

Readily 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 life

Approximately 8 hours.

ClearanceNot Available
Toxicity

Oral 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
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AmodiaquineThe serum concentration of Diethylcarbamazine can be decreased when it is combined with Amodiaquine.Approved
ChloroquineThe serum concentration of Diethylcarbamazine can be decreased when it is combined with Chloroquine.Approved, Vet Approved
HydroxychloroquineThe serum concentration of Diethylcarbamazine can be decreased when it is combined with Hydroxychloroquine.Approved
PrimaquineThe serum concentration of Diethylcarbamazine can be decreased when it is combined with Primaquine.Approved
Food InteractionsNot 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 ReferencesNot Available
External Links
ATC CodesP02CB02 — Diethylcarbamazine
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (65.5 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentLoiasis1
2Active Not RecruitingTreatmentLymphatic Filariasis1
2CompletedTreatmentLymphatic Filariasis1
4CompletedBasic ScienceLoa Loa / Loiasis1
4CompletedTreatmentFilarial; Infestation1
Not AvailableActive Not RecruitingNot AvailableLymphatic Filariasis / Soil Transmitted Helminth Infections1
Not AvailableActive Not RecruitingPreventionLymphatic Filariasis1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lymphatic Filariasis1
Pharmacoeconomics
Manufacturers
  • Lederle laboratories div american cyanamid co
PackagersNot Available
Dosage forms
FormRouteStrength
TabletOral50 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)150-155Kushner, 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 Solubility236.0 mg/mLALOGPS
logP0.9ALOGPS
logP0.092ChemAxon
logS0.07ALOGPS
pKa (Strongest Basic)6.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.79 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity58.28 m3·mol-1ChemAxon
Polarizability22.89 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9746
Blood Brain Barrier+0.9851
Caco-2 permeable+0.5947
P-glycoprotein substrateSubstrate0.7326
P-glycoprotein inhibitor INon-inhibitor0.6368
P-glycoprotein inhibitor IINon-inhibitor0.9745
Renal organic cation transporterNon-inhibitor0.6243
CYP450 2C9 substrateNon-substrate0.8563
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.595
CYP450 1A2 substrateNon-inhibitor0.8168
CYP450 2C9 inhibitorNon-inhibitor0.882
CYP450 2D6 inhibitorNon-inhibitor0.8952
CYP450 2C19 inhibitorNon-inhibitor0.9141
CYP450 3A4 inhibitorNon-inhibitor0.9891
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9614
Ames testNon AMES toxic0.8203
CarcinogenicityNon-carcinogens0.9183
BiodegradationNot ready biodegradable0.85
Rat acute toxicity2.2639 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5
hERG inhibition (predictor II)Non-inhibitor0.7766
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Download (11 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as piperazine carboxamides. These are heterocyclic compounds containing a piperazine ring substituted by one or more carboxamide group.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganoheterocyclic compounds
Sub ClassDiazinanes
Direct ParentPiperazine carboxamides
Alternative ParentsN-methylpiperazines / Ureas / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
SubstituentsPiperazine-1-carboxamide / N-methylpiperazine / N-alkylpiperazine / Tertiary amine / Tertiary aliphatic amine / Urea / Azacycle / Amine / Hydrocarbon derivative / Organic oxide
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsN-methylpiperazine, N-carbamoylpiperazine (CHEBI:4527 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Iron ion binding
Specific Function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Uniprot Name:
Arachidonate 5-lipoxygenase
Molecular Weight:
77982.595 Da
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:3004501 ]
  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:8606397 ]
  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:1886988 ]
  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:10518442 ]
  5. Davidson D, Drafta D: Prolonged pulmonary hypertension caused by platelet-activating factor and leukotriene C4 in the rat lung. J Appl Physiol (1985). 1992 Sep;73(3):955-61. [PubMed:1400062 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Uniprot Name:
Prostaglandin G/H synthase 1
Molecular Weight:
68685.82 Da
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:15932636 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
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
Uniprot Name:
Cholinesterase
Molecular Weight:
68417.575 Da
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:2609206 ]
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:52