Identification

Name
Diethylcarbamazine
Accession Number
DB00711  (APRD00918)
Type
Small Molecule
Groups
Approved, Investigational, 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 Key
Diethylcarbamazine CitrateOS1Z389K8S1642-54-2PGNKBEARDDELNB-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hetrazan Tab 50mgTablet50 mgOralLederle Cyanamid Canada Inc.1982-05-312000-08-02Canada
International/Other Brands
Banocide (GlaxoSmithKline) / Banocide Forte (GlaxoSmithKline) / Carbilazine / Caricide / Cypip / Decet (RND Labs) / Dicarb (Inga) / Diethizine (Pond's Chemical) / Eofil / Ethodryl / Hetrazan (Wyeth) / Notezine (Sanofi-Aventis) / Spatonin / Supatonin (Tanabe Mitsubishi Pharma)
Categories
UNII
V867Q8X3ZD
CAS number
90-89-1
Weight
Average: 199.2932
Monoisotopic: 199.168462309
Chemical Formula
C10H21N3O
InChI Key
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

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.

TargetActionsOrganism
AArachidonate 5-lipoxygenase
inhibitor
Human
UProstaglandin G/H synthase 1
inhibitor
Human
Absorption

Readily absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Partially metabolized to diethylcarbamazine N-oxide.

Route of elimination
Not Available
Half life

Approximately 8 hours.

Clearance
Not 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
Pathways
Not 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, Investigational
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 Interactions
Not 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 References
Not Available
External Links
Human Metabolome Database
HMDB14849
KEGG Drug
D00803
KEGG Compound
C07968
PubChem Compound
3052
PubChem Substance
46506830
ChemSpider
2944
BindingDB
50024883
ChEBI
4527
ChEMBL
CHEMBL684
Therapeutic Targets Database
DAP000914
PharmGKB
PA164748883
Wikipedia
Diethylcarbamazine
ATC Codes
P02CB02 — Diethylcarbamazine
MSDS
Download (65.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentLymphatic Filariasis1
2CompletedTreatmentLoiasis1
2CompletedTreatmentLymphatic Filariasis1
4CompletedBasic ScienceLoa Loa / Loiasis1
4CompletedTreatmentFilarial; Infestation1
Not AvailableActive Not RecruitingPreventionLymphatic Filariasis1
Not AvailableCompletedNot AvailableLymphatic Filariasis / Soil Transmitted Helminth Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lymphatic Filariasis1

Pharmacoeconomics

Manufacturers
  • Lederle laboratories div american cyanamid co
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as piperazine carboxamides. These are heterocyclic compounds containing a piperazine ring substituted by one or more carboxamide group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
Piperazine carboxamides
Alternative Parents
N-methylpiperazines / Ureas / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Piperazine-1-carboxamide / N-alkylpiperazine / N-methylpiperazine / Carbonic acid derivative / Tertiary amine / Tertiary aliphatic amine / Urea / Azacycle / Amine / Hydrocarbon derivative
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
N-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 gas...
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 December 01, 2017 17:18