Identification

Summary

Ranolazine is an anti-anginal drug used for the treatment of chronic angina.

Brand Names
Ranexa
Generic Name
Ranolazine
DrugBank Accession Number
DB00243
Background

Chronic angina is a common cardiovascular condition affecting millions worldwide and causes significant disability while interfering with daily activities.11 Ranolazine is a well-tolerated piperazine derivative used for the management of this condition, offering relief from uncomfortable and debilitating symptoms.17 With a mechanism of action different from drugs used to treat the same condition, ranolazine is a promising anti-anginal therapy. It was originally approved by the FDA in 2006.15

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 427.5365
Monoisotopic: 427.247106559
Chemical Formula
C24H33N3O4
Synonyms
  • Ranolazina
  • Ranolazine
External IDs
  • CVT-303
  • RS-43285-003

Pharmacology

Indication

Ranolazine is indicated for the treatment of chronic angina. It can be used alone or in conjunction with nitrates, beta-blockers, angiotensin receptor blockers, anti-platelet drugs, calcium channel blockers, lipid-lowering drugs, and ACE inhibitors.17

Ranolazine has also been used off-label for the treatment of certain arrhythmias, including ventricular tachycardia, however, this use is not strongly supported by scientific evidence.3 Ranolazine has also been studied for the treatment of acute coronary syndrome, microvascular coronary dysfunction, arrhythmia, and glycemic control, which are not yet approved indications.1,17

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Ranolazine exerts both antianginal and ischemic effects independent from lowering heart rate or blood pressure.9,17 It blocks IKr, the rapid portion of the delayed rectifier potassium current, and prolongs the QTc interval in a dose-dependent fashion. The Ikr is important for cardiac repolarization.17 Ranolazine exerts its therapeutic effects without negative chronotropic, dromotropic, or inotropic actions neither at rest, nor during exercise.1

Mechanism of action

Myocardial ischemia exerts effects on adenosine triphosphate flux, leading to a decrease in the energy available for contraction and relaxation of the heart muscle. Electrolyte balance of sodium and potassium is necessary for maintaining normal cardiac contraction and relaxation. Disruption of adequate sodium and potassium electrolyte balance leads to excessively high concentrations of sodium and calcium, which likely interferes with oxygen supply to the heart muscle. This imbalance eventually leads to angina symptoms of chest pain or pressure, nausea, and dizziness, among others.11,18

The mechanism of action for ranolazine is not fully understood. At therapeutic concentrations, it can inhibit the cardiac late sodium 205 current (INa), which may affect the electrolyte balance in the myocardium, relieving angina symptoms. The clinical significance this inhibition in the treatment of angina symptoms is not yet confirmed.17

Ranolazine inhibits sodium and potassium ion channel currents.1 It has been shown to exert weak activity on L-type calcium channels making it a weak direct vasodilator and exerts minimal direct effects on atrioventricular nodal conduction.2 Some additional mechanisms have been elucidated. Ranolazine exerts antagonistic activity towards the alpha 1 and beta 1 adrenergic receptors and inhibition of fatty acid oxidation.1,12

TargetActionsOrganism
USodium channel protein
inhibitor
Humans
UInward rectifier potassium channel
inhibitor
Humans
UVoltage gated L-type calcium channel
inhibitor
Humans
NAlpha-1 adrenergic receptors
antagonist
Humans
NBeta-1 adrenergic receptor
antagonist
Humans
UFatty acid
other/unknown
Absorption

The time to reach peak serum concentration is quite variable but has been observed to be in the range of 2-6 hours, with steady-state within 3 days.1 The FDA indicates a Tmax of 3-5 hours.17 The average steady-state Cmax is about 2600 ng/mL. Absorption of ranolazine is not significantly affected by food consumption.3 The bioavailability of ranolazine taken in the tablet form compared to that from a solution of ranolazine is about 76%.17

Volume of distribution

The mean apparent volume of distribution of ranolazine is reported to be 53.2 L16 and the average steady-state volume of distribution is estimated to range from 85 to 180 L.6

Protein binding

Approximately 62% of the administered dose of ranolazine is bound to plasma proteins.4,17 Ranolazine appears to have a higher binding affinity for alpha-1 acid glycoprotein.13,16

Metabolism

Ranolazine is rapidly heavily metabolized in the liver an gastrointestinal tract through the activity of the CYP3A4 enzyme with minor contributions from CYP2D6.1,2,17 More than 40 ranolazine metabolites have been found in plasma and more than 100 metabolites have been identified in the urine.4

Ranolazine and some of its metabolites are known to weakly inhibit CYP3A4. However, the activity of the metabolites of ranolazine has not been fully elucidated.16

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Route of elimination

From the administered dose, about 3/4 of the dose is excreted renally, while 1/4 of the dose is excreted in the feces. An estimated 5% of an ingested dose is excreted as unchanged drug.1,17

Half-life

The apparent terminal half-life of ranolazine is 7 hours.13,17

Clearance

The reported clearance rate of orally administered ranolazine is of 45 L/h when administered at a dose of 500 mg twice daily.6 The clearance rate of ranolazine is dose-dependent and renal impairment can increase ranolazine serum concentration by 40-50%.4

Adverse Effects
Adverseeffects
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Toxicity

The reported LD50 of oral ranolazine in the rat is 980 mg/kg.MSDS High oral doses of ranolazine have led to dizziness, nausea, and vomiting. These effects have been shown to be dose related. High intravenous doses can cause diplopia, confusion, paresthesia, in addition to syncope. In the case of an overdose, provide supportive therapy accompanied by continuous ECG monitoring for QT interval prolongation.17

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirRanolazine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Ranolazine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Ranolazine can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Ranolazine.
AbirateroneThe metabolism of Ranolazine can be decreased when combined with Abiraterone.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Ranolazine.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Ranolazine.
AceclofenacAceclofenac may decrease the excretion rate of Ranolazine which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Ranolazine which could result in a higher serum level.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Ranolazine.
Interactions
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Food Interactions
  • Avoid grapefruit products.
  • Take with or without food. The absorption is unaffected by food.

Products

Products2
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Product Ingredients
IngredientUNIICASInChI Key
Ranolazine hydrochlorideF71253DJUN95635-56-6RJNSNFZXAZXOFX-UHFFFAOYSA-N
Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
CorzynaTablet, extended release500 mgOralKye Pharmaceuticals Inc.2021-05-03Not applicableCanada flag
CorzynaTablet, extended release1000 mgOralKye Pharmaceuticals Inc.Not applicableNot applicableCanada flag
RanexaTablet, extended release375 mgOralMenarini International Operations Luxembourg S.A. (Miol)2020-12-16Not applicableEU flag
RanexaTablet, extended release375 mgOralMenarini International Operations Luxembourg S.A. (Miol)2020-12-16Not applicableEU flag
RanexaTablet, extended release750 mgOralMenarini International Operations Luxembourg S.A. (Miol)2020-12-16Not applicableEU flag
RanexaTablet, film coated, extended release500 mg/1OralGilead Sciences2006-01-27Not applicableUS flag61958 100120180907 15195 1vtc5i
RanexaTablet, film coated, extended release500 mg/1OralAphena Pharma Solutions Tennessee, Inc.2006-01-27Not applicableUS flag
RanexaTablet, extended release500 mgOralMenarini International Operations Luxembourg S.A. (Miol)2020-12-16Not applicableEU flag
RanexaTablet, extended release500 mgOralMenarini International Operations Luxembourg S.A. (Miol)2020-12-16Not applicableEU flag
RanexaTablet, film coated, extended release500 mg/1OralGilead Palo Alto, Inc.2006-01-272013-03-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RanolazineTablet, extended release500 mg/1OralSun Pharmaceutical Industries, Inc.2019-05-28Not applicableUS flag
RanolazineTablet, film coated, extended release1000 mg/1OralScieGen Pharmaceuticals, Inc2019-06-04Not applicableUS flag
RanolazineTablet, film coated, extended release500 mg/1OralPraxgen Pharmaceuticals LLC2020-04-01Not applicableUS flag
RanolazineTablet, film coated, extended release500 mg/1OralAphena Pharma Solutions - Tennessee, LLC2019-06-04Not applicableUS flag
RanolazineTablet, film coated, extended release1000 mg/1OralAscend Laboratories, LLC2020-12-02Not applicableUS flag
RanolazineTablet, film coated, extended release500 mg/1OralAphena Pharma Solutions - Tennessee, LLC2020-10-27Not applicableUS flag
RanolazineTablet, film coated, extended release500 mg/1OralGlenmark Pharmaceuticals Inc., USA2019-07-05Not applicableUS flag
RanolazineTablet, film coated, extended release1000 mg/1OralGolden State Medical Supply2019-06-04Not applicableUS flag
RanolazineTablet, extended release1000 mg/1OralAjanta Pharma USA Inc.2019-08-23Not applicableUS flag
RanolazineTablet, film coated, extended release500 mg/1OralLupin Pharmaceuticals, Inc.2019-02-27Not applicableUS flag

Categories

ATC Codes
C01EB18 — Ranolazine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Anisoles
Direct Parent
Anisoles
Alternative Parents
m-Xylenes / Phenoxy compounds / Methoxybenzenes / N-alkylpiperazines / Alkyl aryl ethers / Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids
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Substituents
1,2-aminoalcohol / 1,4-diazinane / Alcohol / Alkyl aryl ether / Amine / Anisole / Aromatic heteromonocyclic compound / Azacycle / Carboximidic acid / Carboximidic acid derivative
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid amide, secondary alcohol, aromatic amide, N-alkylpiperazine, monomethoxybenzene (CHEBI:87690)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
A6IEZ5M406
CAS number
95635-55-5
InChI Key
XKLMZUWKNUAPSZ-UHFFFAOYSA-N
InChI
InChI=1S/C24H33N3O4/c1-18-7-6-8-19(2)24(18)25-23(29)16-27-13-11-26(12-14-27)15-20(28)17-31-22-10-5-4-9-21(22)30-3/h4-10,20,28H,11-17H2,1-3H3,(H,25,29)
IUPAC Name
N-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide
SMILES
COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1

References

Synthesis Reference

Gilla Goverdhan, Anumula Raghupathi, Reddy Aalla, Sampath Kurella, Srinivas Vurimidi, Himabindu Ghanta, Mahesh Reddy.(2019).Improved Process for Ranolazine. Organic Process Research & Development 2009, 13, 1, 67-72

US20110151258
General References
  1. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  2. Saad M, Mahmoud A, Elgendy IY, Richard Conti C: Ranolazine in Cardiac Arrhythmia. Clin Cardiol. 2016 Mar;39(3):170-8. doi: 10.1002/clc.22476. Epub 2015 Oct 13. [Article]
  3. Reed M, Nicolas D: Ranolazine . [Article]
  4. Mezincescu A, Karthikeyan VJ, Nadar SK: Ranolazine: A true pluripotent cardiovascular drug or jack of all trades, master of none? Sultan Qaboos Univ Med J. 2018 Feb;18(1):e13-e23. doi: 10.18295/squmj.2018.18.01.003. Epub 2018 Apr 4. [Article]
  5. Codolosa JN, Acharjee S, Figueredo VM: Update on ranolazine in the management of angina. Vasc Health Risk Manag. 2014 Jun 24;10:353-62. doi: 10.2147/VHRM.S40477. eCollection 2014. [Article]
  6. Jerling M: Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-91. doi: 10.2165/00003088-200645050-00003. [Article]
  7. Thomas D, Karle CA, Kiehn J: The cardiac hERG/IKr potassium channel as pharmacological target: structure, function, regulation, and clinical applications. Curr Pharm Des. 2006;12(18):2271-83. doi: 10.2174/138161206777585102. [Article]
  8. Balestrini S, Sisodiya SM: Pharmacogenomics in epilepsy. Neurosci Lett. 2018 Feb 22;667:27-39. doi: 10.1016/j.neulet.2017.01.014. Epub 2017 Jan 10. [Article]
  9. Gomberg-Maitland M, Schilz R, Mediratta A, Addetia K, Coslet S, Thomeas V, Gillies H, Oudiz RJ: Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulm Circ. 2015 Dec;5(4):691-700. doi: 10.1086/683813. [Article]
  10. Zweiker R, Aichinger J, Metzler B, Lang I, Wallner E, Delle-Karth G: Ranolazine: impact on quality of life in patients with stable angina pectoris, results from an observational study in Austria - the ARETHA AT study. Wien Klin Wochenschr. 2019 Apr;131(7-8):165-173. doi: 10.1007/s00508-019-1481-x. Epub 2019 Apr 8. [Article]
  11. Reddy BM, Weintraub HS, Schwartzbard AZ: Ranolazine: a new approach to treating an old problem. Tex Heart Inst J. 2010;37(6):641-7. [Article]
  12. Bhandari B, Subramanian L: Ranolazine, a partial fatty acid oxidation inhibitor, its potential benefit in angina and other cardiovascular disorders. Recent Pat Cardiovasc Drug Discov. 2007 Jan;2(1):35-9. doi: 10.2174/157489007779606095. [Article]
  13. Chaitman BR: Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006 May 23;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500. [Article]
  14. FDA approvals [Link]
  15. FDA approvals [Link]
  16. Australian Assessment Report [Link]
  17. FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
  18. Angina: Mayo clinic [Link]
  19. RANEXA (ranolazine) Australian report [File]
Human Metabolome Database
HMDB0014388
PubChem Compound
56959
PubChem Substance
46505145
ChemSpider
51354
BindingDB
50173335
RxNav
35829
ChEBI
87690
ChEMBL
CHEMBL1404
Therapeutic Targets Database
DAP000875
PharmGKB
PA164746007
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ranolazine
FDA label
Download (153 KB)
MSDS
Download (52.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableChronic Angina1
4CompletedSupportive CareHypertrophic Cardiomyopathy (HCM)1
4CompletedTreatmentAngina Pectoris / Coronary Artery Disease (CAD) / Type 2 Diabetes Mellitus1
4CompletedTreatmentCardiomyopathy / Chest Pain / Dyspnea1
4CompletedTreatmentCardiovascular Disease (CVD) / End Stage Renal Disease (ESRD)1
4CompletedTreatmentChronic Stable Angina Pectoris1
4CompletedTreatmentLeft Ventricular Diastolic Dysfunction / Pulmonary Hypertension (PH)1
4CompletedTreatmentMicrovascular Angina1
4CompletedTreatmentMyocardial Ischemia / Myocardial Perfusion Imaging1
4CompletedTreatmentPulmonary Hypertension (PH)2

Pharmacoeconomics

Manufacturers
  • Gilead sciences inc
Packagers
  • Atlantic Biologicals Corporation
  • DSM Corp.
  • Gilead Sciences Inc.
Dosage Forms
FormRouteStrength
Tablet, extended releaseOral1000 mg
Tablet, extended releaseOral
Tablet, film coated, extended releaseOral1000 mg/1
Tablet, film coated, extended releaseOral500 mg/1
Tablet, extended releaseOral375 mg
Tablet, extended releaseOral500 mg
Tablet, extended releaseOral750 mg
Tablet, film coated, extended releaseOral375 mg
Tablet, film coated, extended releaseOral500 mg
Tablet, film coated, extended releaseOral750 mg
TabletOral1000 mg/1
TabletOral500 mg/1
Tablet, extended releaseOral1 g/1
Tablet, extended releaseOral1000 mg/1
Tablet, extended releaseOral500 mg/1
Prices
Unit descriptionCostUnit
Ranexa 1000 mg 12 Hour tablet6.89USD tablet
Ranexa 1000 mg tablet6.63USD tablet
Ranexa 500 mg 12 Hour tablet4.06USD tablet
Ranexa 500 mg tablet4.04USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6303607No2001-10-162019-05-27US flag
US6479496No2002-11-122019-05-27US flag
US6525057No2003-02-252019-05-27US flag
US6562826No2003-05-132019-05-27US flag
US6620814No2003-09-162019-05-27US flag
US6852724No2005-02-082019-05-27US flag
US6864258No2005-03-082019-05-27US flag
US6617328No2003-09-092019-05-27US flag
US6369062No2002-04-092019-05-27US flag
US6503911No2003-01-072019-05-27US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)120-124 https://s3-us-west-2.amazonaws.com/drugbank/msds/DB00243.pdf?1550621114
boiling point (°C)624.1 https://pubchem.ncbi.nlm.nih.gov/compound/Ranolazine
water solubility<1 mg/mlMSDS
logP2.07Australian Assessment Report
pKa2.2Australian Assessment Report
Predicted Properties
PropertyValueSource
Water Solubility0.11 mg/mLALOGPS
logP2.08ALOGPS
logP2.83ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)13.6ChemAxon
pKa (Strongest Basic)7.17ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.27 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity123.46 m3·mol-1ChemAxon
Polarizability47.22 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.7425
Blood Brain Barrier-0.5334
Caco-2 permeable-0.5853
P-glycoprotein substrateSubstrate0.8667
P-glycoprotein inhibitor IInhibitor0.7566
P-glycoprotein inhibitor IIInhibitor0.7524
Renal organic cation transporterNon-inhibitor0.7648
CYP450 2C9 substrateNon-substrate0.7965
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7456
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.8287
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8155
Ames testNon AMES toxic0.8529
CarcinogenicityNon-carcinogens0.9128
BiodegradationNot ready biodegradable0.9936
Rat acute toxicity2.3256 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8753
hERG inhibition (predictor II)Inhibitor0.8775
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0010900000-41c6c10d624710416f8e
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-1321900000-58e490b47155b2267ecc
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-1320900000-9a6cdfcd606e98d38452
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-0320900000-ab04122e7d0d6e7c3690
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-5951300000-885e790d3cd4d8746c02

Targets

Drugtargets2
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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Learn more
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Ranolazine administered at normal therapeutic doses can inhibit the cardiac late sodium 205 current (INa), according to the FDA label.
General Function
Voltage-gated sodium channel activity
Specific Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a...

Components:
References
  1. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  2. Saad M, Mahmoud A, Elgendy IY, Richard Conti C: Ranolazine in Cardiac Arrhythmia. Clin Cardiol. 2016 Mar;39(3):170-8. doi: 10.1002/clc.22476. Epub 2015 Oct 13. [Article]
  3. Jerling M: Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-91. doi: 10.2165/00003088-200645050-00003. [Article]
  4. Australian Assessment Report [Link]
  5. FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Inward rectifier potassium channel activity
Specific Function
Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable...

Components:
References
  1. Saad M, Mahmoud A, Elgendy IY, Richard Conti C: Ranolazine in Cardiac Arrhythmia. Clin Cardiol. 2016 Mar;39(3):170-8. doi: 10.1002/clc.22476. Epub 2015 Oct 13. [Article]
  2. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  3. FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
References
  1. Saad M, Mahmoud A, Elgendy IY, Richard Conti C: Ranolazine in Cardiac Arrhythmia. Clin Cardiol. 2016 Mar;39(3):170-8. doi: 10.1002/clc.22476. Epub 2015 Oct 13. [Article]
  2. Peters CH, Sokolov S, Rajamani S, Ruben PC: Effects of the antianginal drug, ranolazine, on the brain sodium channel Na(V)1.2 and its modulation by extracellular protons. Br J Pharmacol. 2013 Jun;169(3):704-16. doi: 10.1111/bph.12150. [Article]
  3. Fredj S, Sampson KJ, Liu H, Kass RS: Molecular basis of ranolazine block of LQT-3 mutant sodium channels: evidence for site of action. Br J Pharmacol. 2006 May;148(1):16-24. doi: 10.1038/sj.bjp.0706709. [Article]
  4. Neshatian L, Strege PR, Rhee PL, Kraichely RE, Mazzone A, Bernard CE, Cima RR, Larson DW, Dozois EJ, Kline CF, Mohler PJ, Beyder A, Farrugia G: Ranolazine inhibits voltage-gated mechanosensitive sodium channels in human colon circular smooth muscle cells. Am J Physiol Gastrointest Liver Physiol. 2015 Sep 15;309(6):G506-12. doi: 10.1152/ajpgi.00051.2015. Epub 2015 Jul 16. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Curator comments
Ranolazine has demonstrated α1 adrenergic antagonist action in animal models and human arteries.
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...

Components:
References
  1. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  2. Virsolvy A, Farah C, Pertuit N, Kong L, Lacampagne A, Reboul C, Aimond F, Richard S: Antagonism of Nav channels and alpha1-adrenergic receptors contributes to vascular smooth muscle effects of ranolazine. Sci Rep. 2015 Dec 10;5:17969. doi: 10.1038/srep17969. [Article]
  3. Zhao G, Walsh E, Shryock JC, Messina E, Wu Y, Zeng D, Xu X, Ochoa M, Baker SP, Hintze TH, Belardinelli L: Antiadrenergic and hemodynamic effects of ranolazine in conscious dogs. J Cardiovasc Pharmacol. 2011 Jun;57(6):639-47. doi: 10.1097/FJC.0b013e31821458e8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Curator comments
Ranolazine has demonstrated B1 antagonist activity in animal models.
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...
Gene Name
ADRB1
Uniprot ID
P08588
Uniprot Name
Beta-1 adrenergic receptor
Molecular Weight
51322.1 Da
References
  1. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  2. Zhao G, Walsh E, Shryock JC, Messina E, Wu Y, Zeng D, Xu X, Ochoa M, Baker SP, Hintze TH, Belardinelli L: Antiadrenergic and hemodynamic effects of ranolazine in conscious dogs. J Cardiovasc Pharmacol. 2011 Jun;57(6):639-47. doi: 10.1097/FJC.0b013e31821458e8. [Article]
  3. Letienne R, Vie B, Puech A, Vieu S, Le Grand B, John GW: Evidence that ranolazine behaves as a weak beta1- and beta2-adrenoceptor antagonist in the rat [correction of cat] cardiovascular system. Naunyn Schmiedebergs Arch Pharmacol. 2001 Apr;363(4):464-71. doi: 10.1007/s002100000378. [Article]
6. Fatty acid
Kind
Group
Organism
Not Available
Pharmacological action
Unknown
Actions
Other/unknown
Curator comments
Ranolazine interrupts the beta-oxidation of fatty acids. The concentration of ranolazine needed to inhibit fatty-acid β-oxidation is at least ten times higher than the therapeutic concentration (<10 µM).
References
  1. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  2. Reddy BM, Weintraub HS, Schwartzbard AZ: Ranolazine: a new approach to treating an old problem. Tex Heart Inst J. 2010;37(6):641-7. [Article]
  3. Bhandari B, Subramanian L: Ranolazine, a partial fatty acid oxidation inhibitor, its potential benefit in angina and other cardiovascular disorders. Recent Pat Cardiovasc Drug Discov. 2007 Jan;2(1):35-9. doi: 10.2174/157489007779606095. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  2. Codolosa JN, Acharjee S, Figueredo VM: Update on ranolazine in the management of angina. Vasc Health Risk Manag. 2014 Jun 24;10:353-62. doi: 10.2147/VHRM.S40477. eCollection 2014. [Article]
  3. Australian Assessment Report [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  5. FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196. [Article]
  2. Codolosa JN, Acharjee S, Figueredo VM: Update on ranolazine in the management of angina. Vasc Health Risk Manag. 2014 Jun 24;10:353-62. doi: 10.2147/VHRM.S40477. eCollection 2014. [Article]
  3. FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Chaitman BR: Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006 May 23;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500. [Article]
  2. Australian Assessment Report [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Saad M, Mahmoud A, Elgendy IY, Richard Conti C: Ranolazine in Cardiac Arrhythmia. Clin Cardiol. 2016 Mar;39(3):170-8. doi: 10.1002/clc.22476. Epub 2015 Oct 13. [Article]
  2. Reed M, Nicolas D: Ranolazine . [Article]
  3. Codolosa JN, Acharjee S, Figueredo VM: Update on ranolazine in the management of angina. Vasc Health Risk Manag. 2014 Jun 24;10:353-62. doi: 10.2147/VHRM.S40477. eCollection 2014. [Article]
  4. Montanari F, Ecker GF: Prediction of drug-ABC-transporter interaction--Recent advances and future challenges. Adv Drug Deliv Rev. 2015 Jun 23;86:17-26. doi: 10.1016/j.addr.2015.03.001. Epub 2015 Mar 11. [Article]
  5. FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
  6. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da
References
  1. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]

Drug created at June 13, 2005 13:24 / Updated at December 08, 2021 01:57