Identification

Name
Carbetocin
Accession Number
DB01282
Type
Small Molecule
Groups
Approved, Investigational
Description

Carbetocin is a drug used to control postpartum hemorrhage, bleeding after giving birth. It is an analogue of oxytocin, and its action is similar to that of oxytocin -- it causes contraction of the uterus.

Structure
Thumb
Synonyms
  • 1-Butanoic acid-2-(O-methyl-L-tyrosine)-1-carbaoxytocin
  • 1-Butyric acid-2-(3-(P-methoxyphenyl)-L-alanine)oxytocin
  • Carbetocina
  • Carbetocino
  • Carbetocinum
  • Deamino-2-O-methyltyrosine-1-carbaoxytocin
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Duratocin InjectionLiquid100 mcgIntravenousFerring Pharmaceuticals1999-08-01Not applicableCanada
Categories
UNII
88TWF8015Y
CAS number
37025-55-1
Weight
Average: 988.161
Monoisotopic: 987.484787417
Chemical Formula
C45H69N11O12S
InChI Key
NSTRIRCPWQHTIA-DTRKZRJBSA-N
InChI
InChI=1S/C45H69N11O12S/c1-6-25(4)38-44(66)51-28(15-16-34(46)57)40(62)52-31(21-35(47)58)41(63)54-32(23-69-18-8-10-37(60)50-30(42(64)55-38)20-26-11-13-27(68-5)14-12-26)45(67)56-17-7-9-33(56)43(65)53-29(19-24(2)3)39(61)49-22-36(48)59/h11-14,24-25,28-33,38H,6-10,15-23H2,1-5H3,(H2,46,57)(H2,47,58)(H2,48,59)(H,49,61)(H,50,60)(H,51,66)(H,52,62)(H,53,65)(H,54,63)(H,55,64)/t25-,28-,29-,30-,31-,32-,33-,38-/m0/s1
IUPAC Name
(2S)-2-{[(2S)-1-[(3R,6S,9S,12S,15S)-12-[(2S)-butan-2-yl]-9-(2-carbamoylethyl)-6-(carbamoylmethyl)-15-[(4-methoxyphenyl)methyl]-5,8,11,14,17-pentaoxo-1-thia-4,7,10,13,16-pentaazacycloicosane-3-carbonyl]pyrrolidin-2-yl]formamido}-N-(carbamoylmethyl)-4-methylpentanamide
SMILES
[H][C@]1(NC(=O)[C@H](CC2=CC=C(OC)C=C2)NC(=O)CCCSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)[C@@H](C)CC

Pharmacology

Indication

Used to control postpartum hemorrhage and bleeding after giving birth.

Associated Conditions
Pharmacodynamics

Carbetocin is a drug used to control postpartum hemorrhage, bleeding after giving birth. It is sold under the trade name Duratocin. It is an analogue of oxytocin, and its action is similar to that of oxytocin; it causes contraction of the uterus.

Mechanism of action

Carbetocin binds to oxytocin receptors present on the smooth musculature of the uterus, resulting in rhythmic contractions of the uterus, increased frequency of existing contractions, and increased uterine tone. The oxytocin receptor content of the uterus is very low in the non-pregnant state, and increases during pregnancy, reaching a peak at the time of delivery.

TargetActionsOrganism
AOxytocin receptor
agonist
Human
Absorption

Bioavailability is 80% following intramuscular injection.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

40 minutes

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Carbetocin.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Carbetocin.
AliskirenThe risk or severity of adverse effects can be increased when Carbetocin is combined with Aliskiren.
AmifostineThe risk or severity of adverse effects can be increased when Amifostine is combined with Carbetocin.
AmilorideThe risk or severity of adverse effects can be increased when Amiloride is combined with Carbetocin.
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Carbetocin.
AmlodipineThe risk or severity of adverse effects can be increased when Amlodipine is combined with Carbetocin.
AmobarbitalAmobarbital may increase the hypotensive activities of Carbetocin.
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Carbetocin.
Amyl NitriteThe risk or severity of adverse effects can be increased when Carbetocin is combined with Amyl Nitrite.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015402
KEGG Drug
D07229
PubChem Compound
16681432
PubChem Substance
46509009
ChemSpider
16736854
BindingDB
50044677
ChEBI
59204
ChEMBL
CHEMBL3301668
Therapeutic Targets Database
DAP000269
PharmGKB
PA164743086
Wikipedia
Carbetocin
ATC Codes
H01BB03 — Carbetocin
AHFS Codes
  • 76:00.00 — Oxytocics

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingNot AvailablePostpartum Haemorrhage (PPH)1
2CompletedScreeningPostpartum Haemorrhage (PPH)1
2, 3CompletedPreventionCesarean Section1
3CompletedPreventionDelivery1
3CompletedPreventionPostpartum Haemorrhage (PPH)2
3CompletedPreventionSevere Pre-eclampsia, Postpartum Condition or Complication1
3CompletedTreatmentObstetrics1
3RecruitingPreventionPostpartum Haemorrhage (PPH)1
3RecruitingTreatmentPost Partum Hemorrhage1
3Unknown StatusPreventionPostpartum Haemorrhage (PPH) / Severe Preeclampsia1
4CompletedNot AvailablePostpartum Haemorrhage (PPH)1
4CompletedPreventionBlood Loss / Postpartum Haemorrhage (PPH)1
4CompletedPreventionPostpartum Haemorrhage (PPH)2
4CompletedSupportive CareEffect of Carbetocin on Cardiovascular System / Pregnancy1
4CompletedTreatmentAnemias / Haemorrhage1
4CompletedTreatmentEffects of; Anesthesia, in Pregnancy1
4CompletedTreatmentPost-Partum Hemorrhage / Uterine Atony1
4Not Yet RecruitingPreventionCesarean Section Complications / Hemodynamics Instability1
4Not Yet RecruitingPreventionPost Partum Hemorrhage1
4Not Yet RecruitingTreatmentCesarean Delivery1
4RecruitingDiagnosticCardiac Arrythmias1
4RecruitingPreventionPostpartum Haemorrhage (PPH)3
4RecruitingTreatmentPregnancy1
4Unknown StatusPreventionCarbetocin for prevention of placental retained1
4Unknown StatusTreatmentPostpartum Haemorrhage (PPH) / Uterine Atony1
Not AvailableCompletedBasic ScienceHyperalgesia / Pain NOS / Sensitization, Central1
Not AvailableCompletedTreatmentAnaesthesia / Pregnancy Related1
Not AvailableCompletedTreatmentPostpartum Haemorrhage (PPH)6
Not AvailableNot Yet RecruitingPreventionCesarean Section Complications1
Not AvailableNot Yet RecruitingPreventionPostpartum Haemorrhage (PPH)1
Not AvailableRecruitingPreventionCesarean Section Complications1
Not AvailableRecruitingTreatmentPostpartum Haemorrhage (PPH)2
Not AvailableUnknown StatusTreatmentPostpartum Haemorrhage (PPH)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidIntravenous100 mcg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP-2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0265 mg/mLALOGPS
logP0.14ALOGPS
logP-3.6ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)11.42ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area362.51 Å2ChemAxon
Rotatable Bond Count18ChemAxon
Refractivity250.18 m3·mol-1ChemAxon
Polarizability101 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9806
Blood Brain Barrier-0.9678
Caco-2 permeable-0.774
P-glycoprotein substrateSubstrate0.8748
P-glycoprotein inhibitor IInhibitor0.5541
P-glycoprotein inhibitor IINon-inhibitor0.8748
Renal organic cation transporterNon-inhibitor0.8938
CYP450 2C9 substrateNon-substrate0.8785
CYP450 2D6 substrateNon-substrate0.7363
CYP450 3A4 substrateSubstrate0.6535
CYP450 1A2 substrateNon-inhibitor0.8997
CYP450 2C9 inhibitorNon-inhibitor0.7966
CYP450 2D6 inhibitorNon-inhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.7442
CYP450 3A4 inhibitorNon-inhibitor0.8166
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9196
Ames testNon AMES toxic0.8318
CarcinogenicityNon-carcinogens0.8517
BiodegradationNot ready biodegradable0.9703
Rat acute toxicity3.2094 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9403
hERG inhibition (predictor II)Inhibitor0.6577
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / Leucine and derivatives / Proline and derivatives / Macrolactams / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Pyrrolidinecarboxamides / Anisoles / Phenoxy compounds / N-acylpyrrolidines
show 14 more
Substituents
Alpha-oligopeptide / Cyclic alpha peptide / Leucine or derivatives / Macrolactam / Proline or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Phenoxy compound
show 32 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
heterodetic cyclic peptide (CHEBI:59204)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Vasopressin receptor activity
Specific Function
Receptor for oxytocin. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
Gene Name
OXTR
Uniprot ID
P30559
Uniprot Name
Oxytocin receptor
Molecular Weight
42770.99 Da
References
  1. Engstrom T, Barth T, Melin P, Vilhardt H: Oxytocin receptor binding and uterotonic activity of carbetocin and its metabolites following enzymatic degradation. Eur J Pharmacol. 1998 Aug 21;355(2-3):203-10. [PubMed:9760035]
  2. Gimpl G, Postina R, Fahrenholz F, Reinheimer T: Binding domains of the oxytocin receptor for the selective oxytocin receptor antagonist barusiban in comparison to the agonists oxytocin and carbetocin. Eur J Pharmacol. 2005 Mar 7;510(1-2):9-16. [PubMed:15740719]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on May 17, 2007 10:46 / Updated on December 10, 2018 13:39