Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C27H36N2O5.BrH |
| Molecular Weight | 549.497 |
| Optical Activity | ( + ) |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Br.COC1=CC2=C(C=C1OC)[C@@H](CN(C)CCCN3CCC4=CC(OC)=C(OC)C=C4CC3=O)C2
InChI
InChIKey=ZVSIMBFKBQCPEX-ZMBIFBSDSA-N
InChI=1S/C27H36N2O5.BrH/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
| Molecular Formula | BrH |
| Molecular Weight | 80.912 |
| 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 |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/16451297
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
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 2.05 µM [IC50] | |||
| 2.29 µM [IC50] | |||
| 2.51 µM [IC50] | |||
| 2.15 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Palliative | CORLANOR Approved UseCorlanor 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 Date2015 |
Cmax
| 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 |
T1/2
| 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 |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes | ||||
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical 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. 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 |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents. | 2008-04 |
|
| Effect of long-term heart rate reduction by If current inhibition on pressure overload-induced heart failure in rats. | 2008-01 |
|
| 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 |
|
| [Selective and specific reduction in the heart rate: a promising direction in the creation of new cardiovascular drugs]. | 2007-12-15 |
|
| Symptom improvement in postural orthostatic tachycardia syndrome with the sinus node blocker ivabradine. | 2007-12 |
|
| The heart rate-lowering agent ivabradine inhibits the pacemaker current I(f) in human atrial myocytes. | 2007-11 |
|
| Heart rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine. | 2007-10-27 |
|
| Modulation of rate by autonomic agonists in SAN cells involves changes in diastolic depolarization and the pacemaker current. | 2007-07 |
|
| Preservation of coronary reserve by ivabradine-induced reduction in heart rate in infarcted rats is associated with decrease in perivascular collagen. | 2007-07 |
|
| Ivabradine: a new strategy for management of stable angina. | 2007-06 |
|
| [Heart rate as a cardiovascular risk factor: potential clinical benefit with ivabradine]. | 2007-05-30 |
|
| I(f) current and heart rate control. | 2007-04 |
|
| Ivabradine: new drug. Best avoided in stable angina. | 2007-04 |
|
| Conversion of post-systolic wall thickening into ejectional thickening by selective heart rate reduction during myocardial stunning. | 2007-04 |
|
| Selective inhibition of the pacemaker channel I(f) improves symptoms in severe dilated cardiomyopathy. | 2007-04 |
|
| Heart rate reduction via selective 'funny' channel blockers. | 2007-04 |
|
| Cellular mechanisms underlying the pharmacological induction of phosphenes. | 2007-02 |
|
| Heart rate reduction by inhibition of If or by beta-blockade has different effects on postsystolic wall thickening. | 2007-02 |
|
| Heart failure management. Interview with Karl Swedberg. | 2007-01-09 |
|
| Use-dependent inhibition of hHCN4 by ivabradine and relationship with reduction in pacemaker activity. | 2007-01 |
|
| 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 |
|
| 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 |
|
| [New drugs; ivabradine]. | 2006-12-02 |
|
| [Heart rate reduction as a therapeutic strategy: novel options]. | 2006-12 |
|
| Comparison of a beta-blocker and an If current inhibitor in rabbits with myocardial infarction. | 2006-12 |
|
| [Ivabradine--a medical alternative for patients with chronic stable angina pectoris]. | 2006-11-13 |
|
| Ivabradine: a selective If current inhibitor in the treatment of stable angina. | 2006-11 |
|
| 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. | 2006-11 |
|
| Heart rate lowering by inhibition of the pacemaker current: a new therapeutic perspective in cardiovascular disease. | 2006-10 |
|
| Lack of pharmacokinetic interaction between omeprazole or lansoprazole and ivabradine in healthy volunteers: an open-label, randomized, crossover, pharmacokinetic interaction clinical trial. | 2006-10 |
|
| Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial. | 2006-10 |
|
| [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 |
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
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on
Edited
Wed Apr 02 10:33:58 GMT 2025
by
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on
Wed Apr 02 10:33:58 GMT 2025
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| Record UNII |
XS8A2GK8EV
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| Record Status |
Validated (UNII)
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| Record Version |
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