Identification
- Summary
Ranolazine is an anti-anginal drug used for the treatment of chronic angina.
- Brand Names
- Aspruzyo Sprinkle, 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
Structure for Ranolazine (DB00243)
- 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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Chronic angina •••••••••••• •••••• Management of Ventricular arrhythmia ••• ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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
Target Actions Organism USodium channel protein inhibitorHumans UInward rectifier potassium channel inhibitorHumans UVoltage gated L-type calcium channel inhibitorHumans NAlpha-1 adrenergic receptors antagonistHumans NBeta-1 adrenergic receptor antagonistHumans 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
Hover over products below to view reaction partners
- 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- 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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Ranolazine may decrease the excretion rate of Abacavir which could result in a higher serum level. Abametapir The serum concentration of Ranolazine can be increased when it is combined with Abametapir. Abatacept The metabolism of Ranolazine can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Ranolazine. Abiraterone The metabolism of Ranolazine can be decreased when combined with Abiraterone. - Food Interactions
- Avoid grapefruit products.
- Take with or without food. The absorption is unaffected by food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Ranolazine hydrochloride F71253DJUN 95635-56-6 RJNSNFZXAZXOFX-UHFFFAOYSA-N - Product Images
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aspruzyo Sprinkle Granule 1000 mg/1 Oral Sun Pharmaceutical Industries, Inc. 2022-02-28 Not applicable US 
Aspruzyo Sprinkle Granule 500 mg/1 Oral Sun Pharmaceutical Industries, Inc. 2022-02-28 Not applicable US Corzyna Tablet, extended release 500 mg Oral Kye Pharmaceuticals Inc. 2021-05-03 Not applicable Canada 
Corzyna Tablet, extended release 1000 mg Oral Kye Pharmaceuticals Inc. 2023-05-24 Not applicable Canada Ranexa Tablet, extended release 500 mg Oral Menarini International Operations Luxembourg S.A. (Miol) 2020-12-16 Not applicable EU 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ranolazine Tablet, film coated, extended release 1000 mg/1 Oral Lupin Pharmaceuticals, Inc. 2019-02-27 Not applicable US Ranolazine Tablet, film coated, extended release 500 mg/1 Oral AvKARE 2020-10-27 Not applicable US Ranolazine Tablet, film coated, extended release 500 mg/1 Oral Proficient Rx LP 2021-08-24 Not applicable US Ranolazine Tablet, extended release 500 mg/1 Oral Sun Pharmaceutical Industries, Inc. 2019-05-28 Not applicable US Ranolazine Tablet, extended release 1000 mg/1 Oral Micro Labs Limited 2020-06-01 Not applicable US
Categories
- ATC Codes
- C01EB18 — Ranolazine
- Drug Categories
- Acetamides
- Antianginal Agents
- BSEP/ABCB11 Substrates
- Cardiac Therapy
- Cardiovascular Agents
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (weak)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- MATE 1 Inhibitors
- MATE 2 Inhibitors
- MATE inhibitors
- Membrane Transport Modulators
- Miscellaneous Cardiac Drugs
- Moderate Risk QTc-Prolonging Agents
- OCT2 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Piperazines
- QTc Prolonging Agents
- Sodium Channel Blockers
- Vasodilating Agents
- 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 show 3 more
- 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
- 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]
- 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]
- Reed M, Nicolas D: Ranolazine . [Article]
- 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]
- 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]
- Jerling M: Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-91. doi: 10.2165/00003088-200645050-00003. [Article]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA approvals [Link]
- FDA approvals [Link]
- Australian Assessment Report [Link]
- FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
- Angina: Mayo clinic [Link]
- RANEXA (ranolazine) Australian report [File]
- External Links
- Human Metabolome Database
- HMDB0014388
- PubChem Compound
- 56959
- PubChem Substance
- 46505145
- ChemSpider
- 51354
- BindingDB
- 50173335
- 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 Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Not Available Chronic Angina 1 4 Completed Supportive Care Hypertrophic Cardiomyopathy (HCM) 1 4 Completed Treatment Angina Pectoris / Coronary Artery Disease (CAD) / Type 2 Diabetes Mellitus 1 4 Completed Treatment Cardiomyopathy / Chest Pain / Dyspnea 1 4 Completed Treatment Cardiovascular Disease (CVD) / End Stage Renal Disease (ESRD) 1
Pharmacoeconomics
- Manufacturers
- Gilead sciences inc
- Packagers
- Atlantic Biologicals Corporation
- DSM Corp.
- Gilead Sciences Inc.
- Dosage Forms
Form Route Strength Granule Oral 1000 mg/1 Granule Oral 500 mg/1 Tablet, extended release Oral 1000 mg Tablet Oral 500.000 mg Tablet, extended release Oral Tablet, film coated, extended release Oral 1000 mg/1 Tablet, film coated, extended release Oral 500 mg/1 Tablet, extended release Oral 375 mg Tablet, extended release Oral 500 mg Tablet, extended release Oral 750 mg Tablet, film coated, extended release Oral 375 mg Tablet, film coated, extended release Oral 500 mg Tablet, film coated, extended release Oral 750 mg Tablet, extended release Oral 100000000 mg Tablet, extended release Oral 50000000 mg Tablet Oral 1000 mg/1 Tablet Oral 500 mg/1 Tablet, extended release Oral 1 g/1 Tablet, extended release Oral 1000 mg/1 Tablet, extended release Oral 500 mg/1 - Prices
Unit description Cost Unit Ranexa 1000 mg 12 Hour tablet 6.89USD tablet Ranexa 1000 mg tablet 6.63USD tablet Ranexa 500 mg 12 Hour tablet 4.06USD tablet Ranexa 500 mg tablet 4.04USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6303607 No 2001-10-16 2019-05-27 US US6479496 No 2002-11-12 2019-05-27 US US6525057 No 2003-02-25 2019-05-27 US US6562826 No 2003-05-13 2019-05-27 US US6620814 No 2003-09-16 2019-05-27 US US6852724 No 2005-02-08 2019-05-27 US US6864258 No 2005-03-08 2019-05-27 US US6617328 No 2003-09-09 2019-05-27 US US6369062 No 2002-04-09 2019-05-27 US US6503911 No 2003-01-07 2019-05-27 US US10898444 No 2021-01-26 2038-01-24 US US11510878 No 2018-01-24 2038-01-24 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source 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/ml MSDS logP 2.07 Australian Assessment Report pKa 2.2 Australian Assessment Report - Predicted Properties
Property Value Source Water Solubility 0.11 mg/mL ALOGPS logP 2.08 ALOGPS logP 2.83 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 13.6 Chemaxon pKa (Strongest Basic) 6.77 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 74.27 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 123.46 m3·mol-1 Chemaxon Polarizability 47.22 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.7425 Blood Brain Barrier - 0.5334 Caco-2 permeable - 0.5853 P-glycoprotein substrate Substrate 0.8667 P-glycoprotein inhibitor I Inhibitor 0.7566 P-glycoprotein inhibitor II Inhibitor 0.7524 Renal organic cation transporter Non-inhibitor 0.7648 CYP450 2C9 substrate Non-substrate 0.7965 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.7456 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.8287 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8155 Ames test Non AMES toxic 0.8529 Carcinogenicity Non-carcinogens 0.9128 Biodegradation Not ready biodegradable 0.9936 Rat acute toxicity 2.3256 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8753 hERG inhibition (predictor II) Inhibitor 0.8775
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 223.7686291 predictedDarkChem Lite v0.1.0 [M-H]- 194.37053 predictedDeepCCS 1.0 (2019) [M+H]+ 223.0475291 predictedDarkChem Lite v0.1.0 [M+H]+ 196.72856 predictedDeepCCS 1.0 (2019) [M+Na]+ 222.5590291 predictedDarkChem Lite v0.1.0 [M+Na]+ 203.81526 predictedDeepCCS 1.0 (2019)
Targets
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- 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
- 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]
- 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]
- Jerling M: Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-91. doi: 10.2165/00003088-200645050-00003. [Article]
- Australian Assessment Report [Link]
- 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
- 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]
- 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]
- 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
- 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]
- 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]
- 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]
- 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:
| Name | UniProt ID |
|---|---|
| Alpha-1A adrenergic receptor | P35348 |
| Alpha-1B adrenergic receptor | P35368 |
| Alpha-1D adrenergic receptor | P25100 |
References
- 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]
- 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]
- 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
- 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]
- 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]
- 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
Unknown
Other/unknown
References
- 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]
- 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]
- 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
- SubstrateInhibitor
- 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
- 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]
- 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]
- Australian Assessment Report [Link]
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
- FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- SubstrateInhibitor
- 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
- 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]
- 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]
- 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
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
- 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
- SubstrateInhibitor
- 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
- 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]
- Reed M, Nicolas D: Ranolazine . [Article]
- 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]
- 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]
- FDA Approved Drug Products: Ranexa (ranolazine) extended-release tablets for oral use [Link]
- 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
- 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
- FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:43