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

Details

Stereochemistry ABSOLUTE
Molecular Formula 2C27H36N2O5.H2O4S
Molecular Weight 1035.249
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of IVABRADINE HEMISULFATE

SMILES

OS(O)(=O)=O.COC1=C(OC)C=C2[C@@H](CN(C)CCCN3CCC4=CC(OC)=C(OC)C=C4CC3=O)CC2=C1.COC5=C(OC)C=C6[C@@H](CN(C)CCCN7CCC8=CC(OC)=C(OC)C=C8CC7=O)CC6=C5

InChI

InChIKey=AMRKLKWJQKOGOF-ITEXDBGESA-N
InChI=1S/2C27H36N2O5.H2O4S/c2*1-28(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;1-5(2,3)4/h2*12-14,16,21H,6-11,15,17H2,1-5H3;(H2,1,2,3,4)/t2*21-;/m11./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
Molecular Formula H2O4S
Molecular Weight 98.078
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
3913
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
471
Targets

Targets

Primary TargetPharmacologyConditionPotency
Blocker
537
 2.05 µM [IC50]
Blocker
537
 2.29 µM [IC50]
Blocker
537
 2.51 µM [IC50]
Blocker
537
 2.15 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8429
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

2015
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
1737

inhibitor
1587
substrate
1037
substrate
1217
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461

CYP2C18
10

CYP2C19
1478

CYP2E1
882

CYP2A6
707

CYP2B6
810

CYP2C8
911
P-gp
1537

BCRP
561

OATP1B1
406

OATP1B3
350

OCT1
327

CYP1A2
1054

CYP2A6
543

CYP2C8
693

CYP2C19
991

CYP2E1
667
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2A6
739
 no
CYP2B6
1001
 no
CYP2C18
13
 no
CYP2C19
1553
 no
CYP2C8
965
 no
CYP2E1
970
 no
CYP3A4
1925
 yes
P-gp
1650
 yes
S 18982
7
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 no [Km 310 uM]
BCRP
561
 no
BCRP
561
 no
S 18982
7
CYP1A2
1054
 no
CYP2A6
543
 no
CYP2C19
991
 no
CYP2C8
693
 no
CYP2C9
1037
 no
CYP2D6
1217
 no
CYP2E1
667
 no
OATP1B1
406
 no
OATP1B1
406
 no
S 18982
7
OATP1B3
350
 no
OATP1B3
350
 no
S 18982
7
OCT1
327
 no
OCT1
327
 no
S 18982
7
CYP3A4
1737
 yes
S 18982
7
P-gp
1537
 yes
S 18982
7
CYP3A4
1737
 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
1647
hERG
1647
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
A single intravenous dose of ivabradine, a novel I(f) inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction.
2003
Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure.
2004 Apr 6
Pharmacokinetics-pharmacodynamics during drug development--an example from Servier: ivabradine.
2004 Mar-Apr
I(f) channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities.
2004 May
Current and future treatment strategies for refractory angina.
2004 Oct
Efficacy and safety of a metabolic modulator drug in chronic stable angina: review of evidence from clinical trials.
2004 Sep
Heart rate reduction: a potential target for the treatment of myocardial ischaemia.
2004 Sep-Oct
[From ischaemia to heart failure: heart rate--actor or stamper?].
2004 Sep-Oct
If at first you don't succeed try ... a new target in the treatment of angina.
2005 Dec
Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina.
2005 Dec
Chronic heart rate reduction remodels ion channel transcripts in the mouse sinoatrial node but not in the ventricle.
2005 Dec 14
[The best of clinical pharmacology in 2004].
2005 Jan
Cardiac pacemaker I(f) current and its inhibition by heart rate-reducing agents.
2005 Jul
Physiology and pharmacology of the cardiac pacemaker ("funny") current.
2005 Jul
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
Impact of increased heart rate on clinical outcomes in hypertension: implications for antihypertensive drug therapy.
2006
Bradycardic and proarrhythmic properties of sinus node inhibitors.
2006 Apr
Properties of ivabradine-induced block of HCN1 and HCN4 pacemaker channels.
2006 Apr 15
[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
Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise.
2006 Feb
[The best of clinical cardiovascular pharmacology in 2005].
2006 Jan
Serious workings of the funny current.
2006 Jan-Apr
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
The discovery of the selective I(f) current inhibitor ivabradine. A new therapeutic approach to ischemic heart disease.
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
Heart rate lowering by inhibition of the pacemaker current: a new therapeutic perspective in cardiovascular disease.
2006 Oct
Perspectives of I(f) inhibition by ivabradine in cardiology.
2007
Clinical results of I(f) current inhibition by ivabradine.
2007
Molecular regulation and pharmacology of pacemaker channels.
2007
Heart rate reduction via selective 'funny' channel blockers.
2007 Apr
Cellular mechanisms underlying the pharmacological induction of phosphenes.
2007 Feb
Use-dependent inhibition of hHCN4 by ivabradine and relationship with reduction in pacemaker activity.
2007 Jan
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
[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
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
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 Sat Dec 16 15:04:35 GMT 2023
Edited
by admin
on Sat Dec 16 15:04:35 GMT 2023
Record UNII
F646VH2WJO
Record Status Validated (UNII)
Record Version
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Name Type Language
IVABRADINE HEMISULFATE
Common Name English
2H-3-BENZAZEPIN-2-ONE, 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-, SULFATE (2:1)
Systematic Name English
Code System Code Type Description
CAS
1422274-66-5
Created by admin on Sat Dec 16 15:04:35 GMT 2023 , Edited by admin on Sat Dec 16 15:04:35 GMT 2023
NON-SPECIFIC STOICHIOMETRY
FDA UNII
F646VH2WJO
Created by admin on Sat Dec 16 15:04:35 GMT 2023 , Edited by admin on Sat Dec 16 15:04:35 GMT 2023
PRIMARY
PUBCHEM
134694287
Created by admin on Sat Dec 16 15:04:35 GMT 2023 , Edited by admin on Sat Dec 16 15:04:35 GMT 2023
PRIMARY
Related Record Type Details
Structure of IVABRADINE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of IVABRADINE
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