U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C27H36N2O5
Molecular Weight 468.5851
Optical Activity ( + )
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IVABRADINE

SMILES

COC1=C(OC)C=C2[C@@H](CN(C)CCCN3CCC4=CC(OC)=C(OC)C=C4CC3=O)CC2=C1

InChI

InChIKey=ACRHBAYQBXXRTO-OAQYLSRUSA-N
InChI=1S/C27H36N2O5/c1-28(17-21-11-20-14-25(33-4)26(34-5)16-22(20)21)8-6-9-29-10-7-18-12-23(31-2)24(32-3)13-19(18)15-27(29)30/h12-14,16,21H,6-11,15,17H2,1-5H3/t21-/m1/s1

HIDE SMILES / InChI
Molecular Formula C27H36N2O5
Molecular Weight 468.5851
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16451297

Ivabradine (CORLANOR®) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If-current, resulting in heart rate reduction at concentrations that do not affect other cardiac ionic currents. Specific heart-rate lowering with ivabradine (CORLANOR®) reduces myocardial oxygen demand, simultaneously improving oxygen supply. It has no negative inotropic or lusitropic effects, preserving ventricular contractility, and does not change any major electrophysiological parameters unrelated to heart rate.

CNS Activity

CNS Active
3828
Curator's Comment: Ivabradine (CORLANOR®) can also inhibit the retinal current Ih. Ih is involved in curtailing retinal responses to bright light stimuli. Under triggering circumstances (e.g., rapid changes in luminosity), partial inhibition of Ih by ivabradine (CORLANOR®) may underlie the luminous phenomena experienced by patients. Luminous phenomena (phosphenes) are described as a transient enhanced brightness in a limited area of the visual field.

Originator

Approval Year

2015
463
Targets

Targets

Primary TargetPharmacologyConditionPotency
Blocker
534
 2.05 µM [IC50]
Blocker
534
 2.29 µM [IC50]
Blocker
534
 2.51 µM [IC50]
Blocker
534
 2.15 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8360
CORLANOR

Approved Use

Corlanor is indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use. Corlanor (ivabradine) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction ≤ 35%, who are in sinus rhythm with resting heart rate ≥ 70 beats per minute and either are on maximally tolerated doses of beta-blockers or have a contraindication to beta-blocker use.

Launch Date

1.429056E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
35.98 ng/mL
EXPERIMENT
https://doi.org/10.1016/j.apsb.2012.01.004
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IVABRADINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
171.19 μg × h/mL
EXPERIMENT
https://doi.org/10.1016/j.apsb.2012.01.004
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IVABRADINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.03 h
EXPERIMENT
https://doi.org/10.1016/j.apsb.2012.01.004
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
IVABRADINE blood
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
10 mg 2 times / day steady, oral
Highest studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
unhealthy, 18–70 years
n = 9
Health Status: unhealthy
Condition: asthma
Age Group: 18–70 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
Other AEs: Nausea, Vision disorders...
Other AEs:
Nausea (1 patient)
Vision disorders (2 patients)
Abdominal pain (1 patient)
Leg pain (1 patient)
Fatigue (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
150 mg single, oral
Overdose
Dose: 150 mg
Route: oral
Route: single
Dose: 150 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
unhealthy, 19 years
n = 1
Health Status: unhealthy
Age Group: 19 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
Other AEs: Dizziness, Nausea...
Other AEs:
Dizziness (1 patient)
Nausea (1 patient)
Vomiting (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
250 mg single, oral
Overdose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/26856350
unknown, 26 years
n = 1
Health Status: unknown
Age Group: 26 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/26856350
Sources:
https://pubmed.ncbi.nlm.nih.gov/26856350
10 mg 2 times / day steady, oral
Highest studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/23755867
healthy, 27.7 years
n = 9
Health Status: healthy
Age Group: 27.7 years
Sex: M
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/23755867
Sources:
https://pubmed.ncbi.nlm.nih.gov/23755867
280 mg single, oral
Overdose
Dose: 280 mg
Route: oral
Route: single
Dose: 280 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/24711296
unhealthy, 47 years
n = 1
Health Status: unhealthy
Age Group: 47 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/24711296
Other AEs: Drowsiness...
Other AEs:
Drowsiness (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/24711296
10 mg 1 times / day multiple, intravenous
Dose: 10 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
unhealthy, 61 years (range: 59 - 67 years)
n = 14
Health Status: unhealthy
Condition: low cardiac output syndrome
Age Group: 61 years (range: 59 - 67 years)
Sex: M+F
Population Size: 14
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
Disc. AE: Bradyarrhythmia, Heart rate decreased...
Other AEs: Pulmonary capillary wedge pressure, Sustained ventricular tachycardia...
AEs leading to
discontinuation/dose reduction:
Bradyarrhythmia (1 patient)
Heart rate decreased (3 patients)
Other AEs:
Pulmonary capillary wedge pressure (5 patients)
Sustained ventricular tachycardia (1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
unhealthy, adult
n = 5477
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 5477
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
Disc. AE: Atrial fibrillation, Heart rate increased...
AEs leading to
discontinuation/dose reduction:
Atrial fibrillation (2.5%)
Heart rate increased (0.5%)
Bradycardia (0.4%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 1 patient
10 mg 2 times / day steady, oral
Highest studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
unhealthy, 18–70 years
n = 9
Health Status: unhealthy
Condition: asthma
Age Group: 18–70 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
Fatigue 1 patient
10 mg 2 times / day steady, oral
Highest studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
unhealthy, 18–70 years
n = 9
Health Status: unhealthy
Condition: asthma
Age Group: 18–70 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
Leg pain 1 patient
10 mg 2 times / day steady, oral
Highest studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
unhealthy, 18–70 years
n = 9
Health Status: unhealthy
Condition: asthma
Age Group: 18–70 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
Nausea 1 patient
10 mg 2 times / day steady, oral
Highest studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
unhealthy, 18–70 years
n = 9
Health Status: unhealthy
Condition: asthma
Age Group: 18–70 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
Vision disorders 2 patients
10 mg 2 times / day steady, oral
Highest studied dose
Dose: 10 mg, 2 times / day
Route: oral
Route: steady
Dose: 10 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
unhealthy, 18–70 years
n = 9
Health Status: unhealthy
Condition: asthma
Age Group: 18–70 years
Sex: M+F
Population Size: 9
Sources:
https://pubmed.ncbi.nlm.nih.gov/18341671
Dizziness 1 patient
150 mg single, oral
Overdose
Dose: 150 mg
Route: oral
Route: single
Dose: 150 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
unhealthy, 19 years
n = 1
Health Status: unhealthy
Age Group: 19 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
Nausea 1 patient
150 mg single, oral
Overdose
Dose: 150 mg
Route: oral
Route: single
Dose: 150 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
unhealthy, 19 years
n = 1
Health Status: unhealthy
Age Group: 19 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
Vomiting 1 patient
150 mg single, oral
Overdose
Dose: 150 mg
Route: oral
Route: single
Dose: 150 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
unhealthy, 19 years
n = 1
Health Status: unhealthy
Age Group: 19 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/32322492
Drowsiness 1 patient
280 mg single, oral
Overdose
Dose: 280 mg
Route: oral
Route: single
Dose: 280 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/24711296
unhealthy, 47 years
n = 1
Health Status: unhealthy
Age Group: 47 years
Sex: M
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/24711296
Sustained ventricular tachycardia 1 patient
10 mg 1 times / day multiple, intravenous
Dose: 10 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
unhealthy, 61 years (range: 59 - 67 years)
n = 14
Health Status: unhealthy
Condition: low cardiac output syndrome
Age Group: 61 years (range: 59 - 67 years)
Sex: M+F
Population Size: 14
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
Bradyarrhythmia 1 patient
Disc. AE
10 mg 1 times / day multiple, intravenous
Dose: 10 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
unhealthy, 61 years (range: 59 - 67 years)
n = 14
Health Status: unhealthy
Condition: low cardiac output syndrome
Age Group: 61 years (range: 59 - 67 years)
Sex: M+F
Population Size: 14
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
Heart rate decreased 3 patients
Disc. AE
10 mg 1 times / day multiple, intravenous
Dose: 10 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
unhealthy, 61 years (range: 59 - 67 years)
n = 14
Health Status: unhealthy
Condition: low cardiac output syndrome
Age Group: 61 years (range: 59 - 67 years)
Sex: M+F
Population Size: 14
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
Pulmonary capillary wedge pressure 5 patients
10 mg 1 times / day multiple, intravenous
Dose: 10 mg, 1 times / day
Route: intravenous
Route: multiple
Dose: 10 mg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
unhealthy, 61 years (range: 59 - 67 years)
n = 14
Health Status: unhealthy
Condition: low cardiac output syndrome
Age Group: 61 years (range: 59 - 67 years)
Sex: M+F
Population Size: 14
Sources:
https://pubmed.ncbi.nlm.nih.gov/30115103
Bradycardia 0.4%
Disc. AE
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
unhealthy, adult
n = 5477
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 5477
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
Heart rate increased 0.5%
Disc. AE
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
unhealthy, adult
n = 5477
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 5477
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
Atrial fibrillation 2.5%
Disc. AE
5 mg 2 times / day steady, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
unhealthy, adult
n = 5477
Health Status: unhealthy
Age Group: adult
Sex: M+F
Population Size: 5477
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000MedR.pdf
Page: p. 171
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1709

inhibitor
1579
substrate
1010
substrate
1193
inhibitor
1599

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1437

CYP2C18
10

CYP2C19
1463

CYP2E1
876

CYP2A6
704

CYP2B6
799

CYP2C8
901
P-gp
1527

BCRP
555

OATP1B1
403

OATP1B3
347

OCT1
322

CYP1A2
1032

CYP2A6
523

CYP2C8
688

CYP2C19
985

CYP2E1
648
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2A6
736
 no
CYP2B6
985
 no
CYP2C18
13
 no
CYP2C19
1537
 no
CYP2C8
955
 no
CYP2E1
964
 no
CYP3A4
1909
 yes
P-gp
1626
 yes
S 18982
7
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1527
 no [Km 310 uM]
BCRP
555
 no
BCRP
555
 no
S 18982
7
CYP1A2
1032
 no
CYP2A6
523
 no
CYP2C19
985
 no
CYP2C8
688
 no
CYP2C9
1010
 no
CYP2D6
1193
 no
CYP2E1
648
 no
OATP1B1
403
 no
OATP1B1
403
 no
S 18982
7
OATP1B3
347
 no
OATP1B3
347
 no
S 18982
7
OCT1
322
 no
OCT1
322
 no
S 18982
7
CYP3A4
1709
 yes
S 18982
7
P-gp
1527
 yes
S 18982
7
CYP3A4
1709
 yes
yes (co-administration study)
Comment: After coadministration of ivabradine with the CYP3A4 inducer St. John’s Wort (Hypericum perforatum) peak and total systemic exposures were reduced ~2-fold.
Page: 6.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1632
hERG
1632
S 18982
7
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:85966
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85966
ChemicalBook
CB41178988
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB41178988
MolPort
MolPort-003-986-484
https://www.molport.com/shop/molecule-link/MolPort-003-986-484
MolPort
MolPort-046-861-860
https://www.molport.com/shop/molecule-link/MolPort-046-861-860
ZINC
ZINC000003805768
http://zinc15.docking.org/substances/ZINC000003805768
PubMed

PubMed

TitleDatePubMed
[Ivabradin (coraxan). One more new approach to fighting myocardial ischemia in patients with ischemic heart disease].
2006
[Why it is necessary to reduce heart rate in the treatment of stable angina?].
2006
[Ivabradine--the first selective and specific I(f) inhibitor, novel preparation for treatment of stable angina].
2006
Future directions: what data do we need?
2006
Heart rate slowing for myocardial dysfunction/heart failure.
2006
Novel If current inhibitor ivabradine: safety considerations.
2006
Heart rate slowing versus other pharmacological antianginal strategies.
2006
Clinical effect of 'pure' heart rate slowing with a prototype If current inhibitor: placebo-controlled experience with ivabradine.
2006
Clinical perspectives of heart rate slowing for coronary event reduction and heart failure.
2006
Heart rate reduction by pharmacological If current inhibition.
2006
If current inhibition: cellular basis and physiology.
2006
[A new medicine for treatment of stable angina pectoris].
2006
[Heart rate reduction as a therapeutic strategy: novel options].
2006 Dec
Comparison of a beta-blocker and an If current inhibitor in rabbits with myocardial infarction.
2006 Dec
[New drugs; ivabradine].
2006 Dec 2
Selective and specific I(f) inhibition: new perspectives for the treatment of stable angina.
2006 Jun
[Possibilities of reducing heart rate by I(f)-channel inhibitors].
2006 Mar 22
Anti-ischaemic effect of ivabradine.
2006 May
Ivabradine: a selective If current inhibitor in the treatment of stable angina.
2006 Nov
Rationale and design of a randomized, double-blind, placebo-controlled trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction: the morBidity-mortality EvAlUaTion of the I(f) inhibitor ivabradine in patients with coronary disease and left ventricULar dysfunction (BEAUTIFUL) study.
2006 Nov
[Ivabradine--a medical alternative for patients with chronic stable angina pectoris].
2006 Nov 13
Heart rate lowering by inhibition of the pacemaker current: a new therapeutic perspective in cardiovascular disease.
2006 Oct
Lack of pharmacokinetic interaction between omeprazole or lansoprazole and ivabradine in healthy volunteers: an open-label, randomized, crossover, pharmacokinetic interaction clinical trial.
2006 Oct
Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial.
2006 Oct
Perspectives of I(f) inhibition by ivabradine in cardiology.
2007
Clinical results of I(f) current inhibition by ivabradine.
2007
If inhibition by Ivabradine. Foreword.
2007
Long-term safety and efficacy of ivabradine in patients with chronic stable angina.
2007
Molecular regulation and pharmacology of pacemaker channels.
2007
Antianginal efficacy and safety of ivabradine compared with amlodipine in patients with stable effort angina pectoris: a 3-month randomised, double-blind, multicentre, noninferiority trial.
2007
I(f) current and heart rate control.
2007 Apr
Ivabradine: new drug. Best avoided in stable angina.
2007 Apr
Conversion of post-systolic wall thickening into ejectional thickening by selective heart rate reduction during myocardial stunning.
2007 Apr
Selective inhibition of the pacemaker channel I(f) improves symptoms in severe dilated cardiomyopathy.
2007 Apr
Heart rate reduction via selective 'funny' channel blockers.
2007 Apr
Symptom improvement in postural orthostatic tachycardia syndrome with the sinus node blocker ivabradine.
2007 Dec
Cellular mechanisms underlying the pharmacological induction of phosphenes.
2007 Feb
Heart rate reduction by inhibition of If or by beta-blockade has different effects on postsystolic wall thickening.
2007 Feb
Use-dependent inhibition of hHCN4 by ivabradine and relationship with reduction in pacemaker activity.
2007 Jan
Heart failure management. Interview with Karl Swedberg.
2007 Jan 9
Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen.
2007 Jul
[Selective and specific reduction in the heart rate: a promising direction in the creation of new cardiovascular drugs].
2007 Jul-Aug
Ivabradine: a new strategy for management of stable angina.
2007 Jun
[Heart rate as a cardiovascular risk factor: potential clinical benefit with ivabradine].
2007 May 30
The heart rate-lowering agent ivabradine inhibits the pacemaker current I(f) in human atrial myocytes.
2007 Nov
Heart rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine.
2007 Oct 27
I f inhibition with ivabradine : electrophysiological effects and safety.
2008
Ivabradine as an alternative therapeutic trial in the therapy of inappropriate sinus tachycardia: a case report.
2008
Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents.
2008 Apr
Effect of long-term heart rate reduction by If current inhibition on pressure overload-induced heart failure in rats.
2008 Jan
Patents

Patents

JP2007112797A
7
US7361649
7
US7361650
7
US7384932
7

Sample Use Guides

In Vivo Use Guide
The recommended starting dose of CORLANOR® is 5 mg twice daily with meals.
Route of Administration: Oral
In Vitro Use Guide
The potential subtype-specificity of the sinus node inhibitors cilobradine, ivabradine, and zatebradine using cyclic nucleotide-gated cation (HCN) channels was tested. All three substances blocked the slow inward current through HCN1, HCN2, HCN3, and HCN4 human channels. There was no subtype-specificity for the steady-state block, with mean IC50 values of 0.99, 2.25, and 1.96 microM for cilobradine, ivabradine, and zatebradine, respectively.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:30:01 UTC 2023
Edited
by admin
on Wed Jul 05 23:30:01 UTC 2023
Record UNII
3H48L0LPZQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IVABRADINE
DASH   EMA EPAR   INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
S-16257
Code English
Ivabradine [WHO-DD]
Common Name English
IVABRADINE [MI]
Common Name English
IVABRADINE [EMA EPAR]
Common Name English
IVABRADINE [MART.]
Common Name English
IVABRADINE [ORANGE BOOK]
Common Name English
3-(3-((((7S)-3,4-DIMETHOXYBICYCLO(4.2.0)OCTA-1,3,5-TRIEN-7-YL)METHYL)METHYLAMINO)PROPYL)-1,3,4,5-TETRAHYDRO-7,8-DIMETHOXY-2H-3-BENZAZEPIN-2-ONE
Systematic Name English
IVABRADINE [USAN]
Common Name English
ivabradine [INN]
Common Name English
Classification Tree Code System Code
WHO-ATC C07FX06
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
FDA ORPHAN DRUG 511915
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
NCI_THESAURUS C47793
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
WHO-ATC C07FX05
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
WHO-VATC QC01EB17
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
FDA ORPHAN DRUG 631818
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
WHO-ATC C01EB17
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
NDF-RT N0000191544
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
Code System Code Type Description
DAILYMED
3H48L0LPZQ
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
IUPHAR
2357
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
NCI_THESAURUS
C65995
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
CHEBI
85969
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
EPA CompTox
DTXSID2048240
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
ChEMBL
CHEMBL471737
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
SMS_ID
100000085462
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
PUBCHEM
132999
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
NDF-RT
N0000191546
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY Hyperpolarization-activated Cyclic Nucleotide-gated Channel Antagonists [MoA]
CAS
155974-00-8
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
DRUG BANK
DB09083
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
USAN
BC-97
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
CHEBI
85966
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
EVMPD
SUB08357MIG
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
INN
7523
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
MERCK INDEX
M6564
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY Merck Index
FDA UNII
3H48L0LPZQ
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
WIKIPEDIA
IVABRADINE
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
DRUG CENTRAL
3312
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY
RXCUI
1649480
Created by admin on Wed Jul 05 23:30:01 UTC 2023 , Edited by admin on Wed Jul 05 23:30:01 UTC 2023
PRIMARY RxNorm
Related Record Type Details
Structure of IVABRADINE HEMISULFATE
SALT/SOLVATE -> PARENT
Structure of IVABRADINE
EXCRETED UNCHANGED
About 4% of unchanged drug was recovered either in urine or in feces, suggesting hepatic metabolism as the major route of elimination. Radioactivity associated with metabolites was excreted to a similar degree in feces (around 45%) and urine (around 37%).
FECAL; URINE
Structure of IVABRADINE ADIPATE
SALT/SOLVATE -> PARENT
Structure of IVABRADINE HYDROBROMIDE
SALT/SOLVATE -> PARENT
Structure of IVABRADINE SULFATE
SALT/SOLVATE -> PARENT
Structure of IVABRADINE OXALATE
SALT/SOLVATE -> PARENT
POTASSIUM/SODIUM HYPERPOLARIZATION-ACTIVATED CYCLIC NUCLEOTIDE-GATED CHANNEL 4
TARGET -> INHIBITOR
IC50
Structure of IVABRADINE HYDROCHLORIDE
SALT/SOLVATE -> PARENT
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Related Record Type Details
Structure of N-DEMETHYLIVABRADINE
METABOLITE ACTIVE -> PARENT
20 mg repeated oral doses in eighteen healthy male volunteers; IVABRADINE 85 + 46 ng/mL
Cmax
PLASMA
Related Record Type Details
Structure of IVABRADINE
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC ORAL ADMINISTRATION

Tmax PHARMACOKINETIC ORAL ADMINISTRATION

NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966