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=C(OC)C=C2[C@@H](CN(C)CCCN3CCC4=CC(OC)=C(OC)C=C4CC3=O)CC2=C1
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1795171 |
2.05 µM [IC50] | ||
Target ID: CHEMBL1795172 |
2.29 µM [IC50] | ||
Target ID: CHEMBL1795173 |
2.51 µM [IC50] | ||
Target ID: CHEMBL1250417 |
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 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
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 |
Doses
Dose | Population | Adverse 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: |
unhealthy, 18–70 years n = 9 Health Status: unhealthy Condition: asthma Age Group: 18–70 years Sex: M+F Population Size: 9 Sources: |
Other AEs: Nausea, Vision disorders... Other AEs: Nausea (1 patient) Sources: Vision disorders (2 patients) Abdominal pain (1 patient) Leg pain (1 patient) Fatigue (1 patient) |
150 mg single, oral Overdose |
unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: |
Other AEs: Dizziness, Nausea... Other AEs: Dizziness (1 patient) Sources: Nausea (1 patient) Vomiting (1 patient) |
250 mg single, oral Overdose |
unknown, 26 years n = 1 Health Status: unknown Age Group: 26 years Sex: F Population Size: 1 Sources: |
|
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: |
healthy, 27.7 years n = 9 Health Status: healthy Age Group: 27.7 years Sex: M Population Size: 9 Sources: |
|
280 mg single, oral Overdose |
unhealthy, 47 years n = 1 Health Status: unhealthy Age Group: 47 years Sex: M Population Size: 1 Sources: |
Other AEs: Drowsiness... |
10 mg 1 times / day multiple, intravenous Dose: 10 mg, 1 times / day Route: intravenous Route: multiple Dose: 10 mg, 1 times / day Sources: |
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: |
Disc. AE: Bradyarrhythmia, Heart rate decreased... Other AEs: Pulmonary capillary wedge pressure, Sustained ventricular tachycardia... AEs leading to discontinuation/dose reduction: Bradyarrhythmia (1 patient) Other AEs:Heart rate decreased (3 patients) Pulmonary capillary wedge pressure (5 patients) Sources: Sustained ventricular tachycardia (1 patient) |
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: Page: p. 171 |
unhealthy, adult n = 5477 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 5477 Sources: Page: p. 171 |
Disc. AE: Atrial fibrillation, Heart rate increased... AEs leading to discontinuation/dose reduction: Atrial fibrillation (2.5%) Sources: Page: p. 171Heart rate increased (0.5%) Bradycardia (0.4%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
unhealthy, 18–70 years n = 9 Health Status: unhealthy Condition: asthma Age Group: 18–70 years Sex: M+F Population Size: 9 Sources: |
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: |
unhealthy, 18–70 years n = 9 Health Status: unhealthy Condition: asthma Age Group: 18–70 years Sex: M+F Population Size: 9 Sources: |
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: |
unhealthy, 18–70 years n = 9 Health Status: unhealthy Condition: asthma Age Group: 18–70 years Sex: M+F Population Size: 9 Sources: |
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: |
unhealthy, 18–70 years n = 9 Health Status: unhealthy Condition: asthma Age Group: 18–70 years Sex: M+F Population Size: 9 Sources: |
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: |
unhealthy, 18–70 years n = 9 Health Status: unhealthy Condition: asthma Age Group: 18–70 years Sex: M+F Population Size: 9 Sources: |
Dizziness | 1 patient | 150 mg single, oral Overdose |
unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: |
Nausea | 1 patient | 150 mg single, oral Overdose |
unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: |
Vomiting | 1 patient | 150 mg single, oral Overdose |
unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: |
Drowsiness | 1 patient | 280 mg single, oral Overdose |
unhealthy, 47 years n = 1 Health Status: unhealthy Age Group: 47 years Sex: M Population Size: 1 Sources: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: |
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: Page: p. 171 |
unhealthy, adult n = 5477 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 5477 Sources: 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: Page: p. 171 |
unhealthy, adult n = 5477 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 5477 Sources: 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: Page: p. 171 |
unhealthy, adult n = 5477 Health Status: unhealthy Age Group: adult Sex: M+F Population Size: 5477 Sources: Page: p. 171 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=57 Page: 57.0 |
||||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206143Orig1s000PharmR.pdf#page=57 Page: 57.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Effects of heart rate reduction with ivabradine on exercise-induced myocardial ischemia and stunning. | 2001 Dec |
|
An identifiability analysis of a parent-metabolite pharmacokinetic model for ivabradine. | 2001 Feb |
|
Optimal design of a population pharmacodynamic experiment for ivabradine. | 2001 Jan |
|
Sinus tachyarrhythmias and the specific bradycardic agents: a marriage made in heaven? | 2003 Jun |
|
Current and future treatment strategies for refractory angina. | 2004 Oct |
|
Heart rate reduction: a potential target for the treatment of myocardial ischaemia. | 2004 Sep-Oct |
|
[Heart rate and experimental myocardial ischaemia]. | 2004 Sep-Oct |
|
[Selection and pharmacological characterisation of Procoralan, a selective inhibitor of the pacemaker If current]. | 2004 Sep-Oct |
|
[From ischaemia to heart failure: heart rate--actor or stamper?]. | 2004 Sep-Oct |
|
Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. | 2005 Dec |
|
[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 |
|
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 |
|
[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 |
|
Funny channels in the control of cardiac rhythm and mode of action of selective blockers. | 2006 May |
|
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 |
|
Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial. | 2006 Oct |
|
Clinical results of I(f) current inhibition by ivabradine. | 2007 |
|
Molecular regulation and pharmacology of pacemaker channels. | 2007 |
|
Symptom improvement in postural orthostatic tachycardia syndrome with the sinus node blocker ivabradine. | 2007 Dec |
|
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 |
|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16387796
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
Edited
Sat Dec 16 18:17:17 GMT 2023
by
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on
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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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