IVABRADINE

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 Search

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
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206143Orig1s002lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1 7 Target ID: CHEMBL1795171 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206143Orig1s002lbl.pdf	Blocker 555	2.05 µM [IC50]
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2 7 Target ID: CHEMBL1795172 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206143Orig1s002lbl.pdf	Blocker 555	2.29 µM [IC50]
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 7 Target ID: CHEMBL1795173 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206143Orig1s002lbl.pdf	Blocker 555	2.51 µM [IC50]
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 14 Target ID: CHEMBL1250417 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206143Orig1s002lbl.pdf	Blocker 555	2.15 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic heart failure 21 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/206143Orig1s002lbl.pdf	Palliative		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
171.19 ng × 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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	substrate 1193	substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 CYP2C18 10 CYP2C19 2057 CYP2E1 1060 CYP2A6 879 CYP2B6 926 CYP2C8 1057	P-gp 2052 BCRP 697 OATP1B1 503 OATP1B3 435 OCT1 393 CYP1A2 1197 CYP2A6 626 CYP2C8 810 CYP2C19 1119 CYP2E1 729

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
CYP2B6 1160	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
CYP2C18 13	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
CYP2C8 1117	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
CYP2E1 1146	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=97 Page: 97.0	yes
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000ClinPharmR.pdf#page=29 Page: 29.0	yes	S 18982 7

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=87 Page: 87.0	no [Km 310 uM]
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
BCRP 697	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=99 Page: 99.0	no	S 18982 7
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=90 Page: 90.0	no
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=90 Page: 90.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=90 Page: 90.0	no
CYP2C8 810	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=90 Page: 90.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=90 Page: 90.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=90 Page: 90.0	no
CYP2E1 729	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=90 Page: 90.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
OATP1B1 503	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=99 Page: 99.0	no	S 18982 7
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
OATP1B3 435	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=99 Page: 99.0	no	S 18982 7
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=98 Page: 98.0	no
OCT1 393	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=99 Page: 99.0	no	S 18982 7
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000ClinPharmR.pdf#page=29 Page: 29.0	yes	S 18982 7
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000ClinPharmR.pdf#page=29 Page: 29.0	yes	S 18982 7
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000ClinPharmR.pdf#page=6 Page: 6.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=57 Page: 57.0
hERG 2263	inhibitor 2237 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=57 Page: 57.0		S 18982 7

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
New agent ivabradine (Procoralan) for treatment of chronic stable angina.	2005 Sep-Oct	16307166
[Ivabradin (coraxan). One more new approach to fighting myocardial ischemia in patients with ischemic heart disease].	2006	17076230
[Why it is necessary to reduce heart rate in the treatment of stable angina?].	2006	17047624
[Ivabradine--the first selective and specific I(f) inhibitor, novel preparation for treatment of stable angina].	2006	17047598
Future directions: what data do we need?	2006	16936476
Heart rate slowing for myocardial dysfunction/heart failure.	2006	16936475
Novel If current inhibitor ivabradine: safety considerations.	2006	16936474
Heart rate slowing versus other pharmacological antianginal strategies.	2006	16936473
Clinical effect of 'pure' heart rate slowing with a prototype If current inhibitor: placebo-controlled experience with ivabradine.	2006	16936472
Clinical perspectives of heart rate slowing for coronary event reduction and heart failure.	2006	16936471
Heart rate reduction by pharmacological If current inhibition.	2006	16936470
If current inhibition: cellular basis and physiology.	2006	16936469
[A new medicine for treatment of stable angina pectoris].	2006	16889061
[Heart rate reduction as a therapeutic strategy: novel options].	2006 Dec	17077980
Comparison of a beta-blocker and an If current inhibitor in rabbits with myocardial infarction.	2006 Dec	17043621
[New drugs; ivabradine].	2006 Dec 2	17205941
[Selective I(f) channel inhibition: an alternative for treating coronary artery disease?].	2006 Feb	16502273
Evolving treatment strategies for chronic refractory angina.	2006 Feb	16448320
[The best of clinical cardiovascular pharmacology in 2005].	2006 Jan	16479971
Selective and specific I(f) inhibition: new perspectives for the treatment of stable angina.	2006 Jun	16732707
[Possibilities of reducing heart rate by I(f)-channel inhibitors].	2006 Mar 22	16802542
Anti-ischaemic effect of ivabradine.	2006 May	16644235
Therapeutic effects of I(f) blockade: evidence and perspective.	2006 May	16621590
Ivabradine: a selective If current inhibitor in the treatment of stable angina.	2006 Nov	18221092
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	17070146
[Ivabradine--a medical alternative for patients with chronic stable angina pectoris].	2006 Nov 13	17125651
Heart rate lowering by inhibition of the pacemaker current: a new therapeutic perspective in cardiovascular disease.	2006 Oct	17073608
Lack of pharmacokinetic interaction between omeprazole or lansoprazole and ivabradine in healthy volunteers: an open-label, randomized, crossover, pharmacokinetic interaction clinical trial.	2006 Oct	16988209
Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial.	2006 Oct	16988208
Perspectives of I(f) inhibition by ivabradine in cardiology.	2007	17999563
Clinical results of I(f) current inhibition by ivabradine.	2007	17999562
Preclinical results with I(f) current inhibition by ivabradine.	2007	17999561
The funny current: cellular basis for the control of heart rate.	2007	17999560
If inhibition by Ivabradine. Foreword.	2007	17999558
Molecular regulation and pharmacology of pacemaker channels.	2007	17692005
I(f) current and heart rate control.	2007 Apr	17546262
Selective inhibition of the pacemaker channel I(f) improves symptoms in severe dilated cardiomyopathy.	2007 Apr	17323011
Heart rate reduction via selective 'funny' channel blockers.	2007 Apr	17267284
Symptom improvement in postural orthostatic tachycardia syndrome with the sinus node blocker ivabradine.	2007 Dec	17951266
Cellular mechanisms underlying the pharmacological induction of phosphenes.	2007 Feb	17211458
Heart rate reduction by inhibition of If or by beta-blockade has different effects on postsystolic wall thickening.	2007 Feb	17179940
Use-dependent inhibition of hHCN4 by ivabradine and relationship with reduction in pacemaker activity.	2007 Jan	17128289
[Selective and specific reduction in the heart rate: a promising direction in the creation of new cardiovascular drugs].	2007 Jul-Aug	18078045
Ivabradine: a new strategy for management of stable angina.	2007 Jun	17639836
[Heart rate as a cardiovascular risk factor: potential clinical benefit with ivabradine].	2007 May 30	17645051
Heart rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine.	2007 Oct 27	17989604
I f inhibition with ivabradine : electrophysiological effects and safety.	2008	18217787
Ivabradine as an alternative therapeutic trial in the therapy of inappropriate sinus tachycardia: a case report.	2008	18057886
Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents.	2008 Apr	18223669
Effect of long-term heart rate reduction by If current inhibition on pressure overload-induced heart failure in rats.	2008 Jan	17901295

Patents

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 `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)`
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Name

Type

Language

IVABRADINE [EMA EPAR]

Preferred Name

English

IVABRADINE

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