IVABRADINE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H36N2O5.ClH
Molecular Weight	505.046
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.COC1=CC2=C(C=C1OC)[C@@H](CN(C)CCCN3CCC4=C(CC3=O)C=C(OC)C(OC)=C4)C2

InChI

InChIKey=HLUKNZUABFFNQS-ZMBIFBSDSA-N

InChI=1S/C27H36N2O5.ClH/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;1H/t21-;/m1./s1

HIDE SMILES / InChI

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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
Clinical trial simulation using therapeutic effect modeling: application to ivabradine efficacy in patients with angina pectoris.	2002 Aug	12518708
Differential effects of heart rate reduction and beta-blockade on left ventricular relaxation during exercise.	2002 Feb	11788417
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	14631136
Contributions of heart rate and contractility to myocardial oxygen balance during exercise.	2003 Feb	12399255
Anti-ischemic effects of ivabradine, a selective heart rate-reducing agent, in exercise-induced myocardial ischemia in pigs.	2003 Nov	14576519
Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease.	2004	15301560
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	14981003
Drug insight: If inhibitors as specific heart-rate-reducing agents.	2004 Dec	16265314
Effect of graded heart rate reduction with ivabradine on myocardial oxygen consumption and diastolic time in exercising dogs.	2004 Jan	14569053
I(f) channel inhibitor ivabradine lowers heart rate in mice with enhanced sympathoadrenergic activities.	2004 May	15066901
Heart rate reduction: a potential target for the treatment of myocardial ischaemia.	2004 Sep-Oct	15648303
[Heart rate and experimental myocardial ischaemia].	2004 Sep-Oct	15648302
[Selection and pharmacological characterisation of Procoralan, a selective inhibitor of the pacemaker If current].	2004 Sep-Oct	15648301
If at first you don't succeed try ... a new target in the treatment of angina.	2005 Dec	16219649
Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina.	2005 Dec	16214830
Chronic heart rate reduction remodels ion channel transcripts in the mouse sinoatrial node but not in the ventricle.	2005 Dec 14	16219869
[The best of clinical pharmacology in 2004].	2005 Jan	15714864
Cardiac pacemaker I(f) current and its inhibition by heart rate-reducing agents.	2005 Jul	16004681
Physiology and pharmacology of the cardiac pacemaker ("funny") current.	2005 Jul	15963351
The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides.	2005 Jul 22	15923185
[Ivabradine -- a novel approach for heart rate lowering].	2005 Jun 17	15942839
New agent ivabradine (Procoralan) for treatment of chronic stable angina.	2005 Sep-Oct	16307166
Novel If current inhibitor ivabradine: safety considerations.	2006	16936474
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
Impact of increased heart rate on clinical outcomes in hypertension: implications for antihypertensive drug therapy.	2006	16451089
Bradycardic and proarrhythmic properties of sinus node inhibitors.	2006 Apr	16387796
Properties of ivabradine-induced block of HCN1 and HCN4 pacemaker channels.	2006 Apr 15	16484306
[Heart rate reduction as a therapeutic strategy: novel options].	2006 Dec	17077980
[New drugs; ivabradine].	2006 Dec 2	17205941
Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina.	2006 Feb	16451297
Evolving treatment strategies for chronic refractory angina.	2006 Feb	16448320
Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise.	2006 Feb	16433867
[The best of clinical cardiovascular pharmacology in 2005].	2006 Jan	16479971
[The discovery of the selective If current inhibitor ivabradine (Procoralan): a new therapeutic approach to ischemic heart disease].	2006 Jan	16386229
Serious workings of the funny current.	2006 Jan-Apr	15975637
Therapeutic effects of I(f) blockade: evidence and perspective.	2006 May	16621590
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
Heart rate lowering by inhibition of the pacemaker current: a new therapeutic perspective in cardiovascular disease.	2006 Oct	17073608
Preclinical results with I(f) current inhibition by ivabradine.	2007	17999561
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	17335297
Conversion of post-systolic wall thickening into ejectional thickening by selective heart rate reduction during myocardial stunning.	2007 Apr	17376788
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
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
Heart failure management. Interview with Karl Swedberg.	2007 Jan 9	17369884
Ivabradine: a new strategy for management of stable angina.	2007 Jun	17639836
I f inhibition with ivabradine : electrophysiological effects and safety.	2008	18217787

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 19:27:01 GMT 2025` Edited by `admin` on `Mon Mar 31 19:27:01 GMT 2025`
Record UNII	TP19837BZK
Record Status	`Validated (UNII)`
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Name

Type

Language

IVABRADINE HYDROCHLORIDE

Official Name

English

CORLANOR

Preferred Name

English

IVABRADINE HYDROCHLORIDE [USAN]

Common Name

English

IVABRADINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

S-16257-2

Code

English

Ivabradine hydrochloride [WHO-DD]

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-, HYDROCHLORIDE (1:1)

Systematic Name

English

IVABRADINE HYDROCHLORIDE [JAN]

Common Name

English

AMG 998

Code

English

CORLENTOR

Brand Name

English

IVABRADINE HYDROCHLORIDE [EMA EPAR]

Common Name

English

IVABRADINE HYDROCHLORIDE [MI]

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 HYDROCHLORIDE

Systematic Name

English

PROCORALAN

Brand Name

English

IVABRADINE HCL

Common Name

English

AMG-998

Code

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

PROCORALAN (AUTHORIZED: ANGINA PECTORIS)