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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=CC2=C(C=C1OC)[C@@H](CN(C)CCCN3CCC4=CC(OC)=C(OC)C=C4CC3=O)C2

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

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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
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
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 ng × h/mL
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
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
OverviewDrug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no [Km 310 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
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
PubMed

PubMed

TitleDatePubMed
New agent ivabradine (Procoralan) for treatment of chronic stable angina.
2005 Sep-Oct
[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 I(f) channel inhibition: an alternative for treating coronary artery disease?].
2006 Feb
Evolving treatment strategies for chronic refractory angina.
2006 Feb
[The best of clinical cardiovascular pharmacology in 2005].
2006 Jan
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
Therapeutic effects of I(f) blockade: evidence and perspective.
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
Preclinical results with I(f) current inhibition by ivabradine.
2007
The funny current: cellular basis for the control of heart rate.
2007
If inhibition by Ivabradine. Foreword.
2007
Molecular regulation and pharmacology of pacemaker channels.
2007
I(f) current and heart rate control.
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
[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
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

Sample Use Guides

The recommended starting dose of CORLANOR® is 5 mg twice daily with meals.
Route of Administration: Oral
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 Mon Mar 31 18:16:53 GMT 2025
Edited
by admin
on Mon Mar 31 18:16:53 GMT 2025
Record UNII
3H48L0LPZQ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IVABRADINE [EMA EPAR]
Preferred Name English
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 [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 Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
FDA ORPHAN DRUG 511915
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
NCI_THESAURUS C47793
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
WHO-ATC C07FX05
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
WHO-VATC QC01EB17
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
FDA ORPHAN DRUG 631818
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
WHO-ATC C01EB17
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
NDF-RT N0000191544
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
Code System Code Type Description
DAILYMED
3H48L0LPZQ
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
IUPHAR
2357
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
NCI_THESAURUS
C65995
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
CHEBI
85969
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
EPA CompTox
DTXSID2048240
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
ChEMBL
CHEMBL471737
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
SMS_ID
100000085462
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
PUBCHEM
132999
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
NDF-RT
N0000191546
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY Hyperpolarization-activated Cyclic Nucleotide-gated Channel Antagonists [MoA]
CAS
155974-00-8
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
DRUG BANK
DB09083
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
USAN
BC-97
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
CHEBI
85966
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
EVMPD
SUB08357MIG
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
INN
7523
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
MERCK INDEX
m6564
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY Merck Index
FDA UNII
3H48L0LPZQ
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
WIKIPEDIA
IVABRADINE
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
DRUG CENTRAL
3312
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY
RXCUI
1649480
Created by admin on Mon Mar 31 18:16:53 GMT 2025 , Edited by admin on Mon Mar 31 18:16:53 GMT 2025
PRIMARY RxNorm
Related Record Type Details
SALT/SOLVATE -> PARENT
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
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
Related Record Type Details
METABOLITE ACTIVE -> PARENT
20 mg repeated oral doses in eighteen healthy male volunteers; IVABRADINE 85 + 46 ng/mL
Cmax
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC ORAL ADMINISTRATION

Tmax PHARMACOKINETIC ORAL ADMINISTRATION