Identification

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Name
Ranolazine
Accession Number
DB00243  (APRD01300)
Type
Small Molecule
Groups
Approved, Investigational
Description

Ranolazine is an acetanilide and piperazine derivative that inhibits the late sodium current.4 It is presented as a racemic form in a ration 1:1 with no inter-conversion.9 The ranolazine product as found today was developed by Lupin Ltd and approved by the FDA in 2013.7 However, the original ranolazine product was developed by CV Therapeutics Inc, FDA approved in 20068 and EMA approved in 2008.4

Structure
Thumb
Synonyms
  • Ranolazina
  • Ranolazine
External IDs
CVT-303 / RS-43285-003
Product Ingredients
IngredientUNIICASInChI Key
Ranolazine hydrochlorideF71253DJUN95635-56-6RJNSNFZXAZXOFX-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RanexaTablet, film coated, extended release1000 mg/1OralGilead Palo Alto, Inc.2007-02-122011-05-31Us
RanexaTablet, film coated, extended release1000 mg/1OralGilead Sciences, Inc.2007-02-12Not applicableUs61958 1004 01 nlmimage10 32431978
RanexaTablet, film coated, extended release500 mg/1OralGilead Sciences, Inc.2006-01-27Not applicableUs61958 100320180907 15195 18u0tsx
RanexaTablet, film coated, extended release500 mg/1OralGilead Palo Alto, Inc.2006-01-272013-03-31Us
RanexaTablet, film coated, extended release500 mg/1OralCardinal Health2007-02-122013-03-31Us61958 1001 01 nlmimage10 e31c7193
RanexaTablet, film coated, extended release1000 mg/1OralGilead Sciences2007-02-12Not applicableUs
RanexaTablet, film coated, extended release500 mg/1OralAphena Pharma Solutions Tennessee, Inc.2006-01-27Not applicableUs
RanexaTablet, film coated, extended release500 mg/1OralGilead Sciences2006-01-27Not applicableUs61958 100120180907 15195 1vtc5i
RanexaTablet, film coated, extended release500 mg/1OralCardinal Health2006-01-272015-12-31Us61958 1003 01 nlmimage10 a83ed476
RanexaTablet, film coated, extended release500 mg/1OralCarilion Materials Management2006-01-27Not applicableUs68151 500420180907 15195 f63t8y
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
RanolazineTablet, film coated, extended release500 mg/1OralGlenmark Pharmaceuticals Inc., USA2019-07-05Not applicableUs
RanolazineTablet, extended release1 g/1OralAmerigen Pharmaceuticals Inc.2019-10-29Not applicableUs
RanolazineTablet, film coated, extended release1000 mg/1OralScieGen Pharmaceuticals, Inc2019-06-04Not applicableUs
RanolazineTablet, extended release500 mg/1OralSun Pharmaceutical Industries, Inc.2019-05-28Not applicableUs
RanolazineTablet, extended release1000 mg/1OralViona Pharmaceuticals Inc2019-09-10Not applicableUs
RanolazineTablet, extended release500 mg/1OralAmerigen Pharmaceuticals Inc.2019-10-29Not applicableUs
RanolazineTablet, film coated, extended release500 mg/1OralAphena Pharma Solutions - Tennessee, LLC2019-06-04Not applicableUs
RanolazineTablet, film coated, extended release500 mg/1OralScieGen Pharmaceuticals, Inc2019-06-04Not applicableUs
RanolazineTablet, film coated, extended release1000 mg/1OralCipla USA Inc.2019-05-28Not applicableUs
RanolazineTablet, extended release500 mg/1OralViona Pharmaceuticals Inc2019-09-10Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
A6IEZ5M406
CAS number
95635-55-5
Weight
Average: 427.5365
Monoisotopic: 427.247106559
Chemical Formula
C24H33N3O4
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

Pharmacology

Indication

Ranolazine is approved as a second-line agent in the management of chronic stable angina pectoris that is refractory to conventional anti-ischemic therapy.2

Ranolazine has also been used off-label for the treatment of some arrhythmias such as ventricular tachycardia, however, this use does not have a lot of supporting evidence.3

The use of ranolazine has been researched in the treatment of acute coronary syndrome, microvascular coronary dysfunction, arrhythmia, and glycemic control.1

Associated Conditions
Pharmacodynamics

The inhibition of the late phase sodium current can reduce the upregulated level of cytosolic calcium. The presence of intracellular calcium overload is key for the reduction of left ventricular relaxation causing ventricular tachycardia.1

The effects of ranolazine on the rectifying potassium current results in prolonged QTc and transmural dispersion of repolarization without inducing ventricular arrhythmias or torsade de pointes as this effect is contrary to the effect towards the sodium channels.2

It has been reported that ranolazine exerts significant depression of the action potential amplitude in atrial myocytes. The inhibition of sodium channels as well as potassium rectifiers produces an opposite reaction, the end effect is highly dependent on the cell type and the degree of contribution of these currents. It is known that sodium channels are greater in M cells and Purkinje fibers in which ranolazine can produce significant shortening of action potential duration. On the same point, ranolazine can produce prolonged action potential duration on epicardial cells and this combined effect on the three cells is the key point for the protective effect against ventricular arrhythmias.2

The effect of ranolazine towards fatty acid was thought to be the main mechanism of action of this therapeutic agent as the reduction of fatty acid oxidation will in order, enhance glucose oxidation, reduce production of lactic acid and improve heart function.3 However, this mechanism of action was later shown to not be the major therapeutic effect-causing mechanism.

In clinical trials for stable angina (MARISA) the use of ranolazine significantly increases the exercise duration while having a negligible effect on heart rate and blood pressure. As well, in other clinical trials (CARISA) the time to angina symptoms and time to ischemia were significantly increased while the angina attacks and nitroglycerin use was reduced by about 7 days in the ranolazine-treated patients.3

Mechanism of action

Ranolazine acts by inhibiting sodium and potassium ion channel currents. This effect is obtained as a result of the inhibition of peak and late sodium channels which in order increases myocardial function.1 The effect of ranolazine in sodium channels is being reported to be tissue-specific as well as frequency- and voltage-dependent for which ranolazine has been proven to be more potent in the setting of tachycardia.2

As well, ranolazine inhibits delayed rectifier potassium currents with an inhibitory concentration of 11.5 microM which in order prolongs the ventricular action potential duration. As well, ranolazine has been shown to have a small activity towards L-type calcium channels making it a weak direct vasodilator and presents a minimal direct effect on atrioventricular nodal conduction.2

In order, the effect of ranolazine is obtained via a combination between the inhibition of the delayed rectifier potassium currents and the inward sodium current inhibition.1

Some other mechanisms have been elucidated in which ranolazine presents antagonistic activity towards the alpha1- and beta1-adrenergic in animal models as well as an inhibitory profile against fatty acid oxidation.1

TargetActionsOrganism
ASodium channel protein
inhibitor
Humans
AInward rectifier potassium channel
inhibitor
Humans
NVoltage gated L-type calcium channel
inhibitor
Humans
NAlpha-1 adrenergic receptors
antagonist
Humans
NBeta-1 adrenergic receptor
antagonist
Humans
NFatty acid
other/unknown
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
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Absorption

The time to reach peak serum concentration is very variable but it has been suggested to be of 2-6 hours and to reach steady-state within 3 days.1 The absorption of ranolazine is not modified by food consumption.3 The bioavailability of ranolazine is reported to be of about 73% counting both the unchanged form and the metabolites. After multiple administration of a dose of 500 mg, the reported Cmax and AUC were 1770 ng/ml and 13700 ng.h/ml respectively.9

Volume of distribution

The mean apparent volume of distribution of ranolazine is reported to be of 53.2 L9 and the mean steady-state volume of distribution is of about 180L.10

Protein binding

In the human body, about 62% of the administered dose of ranolazine is bound to proteins.4 From the studies related to binding in plasma proteins, ranolazine seems to have a higher affinity for alpha-1 acid glycoprotein.10

Metabolism

Ranolazine is greatly metabolized in the liver an intestine via the activity of cytochrome P450, from which the isoform CYP3A4 presents the main role and CYP2D6 presents minor importance.1 The metabolism of ranolazine has reported more than 40 metabolites in plasma and more than 100 metabolites in urine.4

From the observed metabolism, there are 4 major metabolites from which RS-88390, as well as the unchanged drug, are known to weakly inhibit CYP3A4. However, the activity of the metabolites of ranolazine has not been fully elucidated.9

Route of elimination

From the administered dose, about 75% is excreted renally.1 From this eliminated dose, only about 5% is represented by the unchanged drug.4

Half life

Due to the short half-life of the immediate release formulation of ranolazine (1.4-1.9 hours), it was required the generation of an extended-release formulation which presented an approximate steady-state half-life of 7-9 hours.1

Clearance

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

Toxicity

The reported LD50 of oral ranolazine in the rat is of 980 mg/kg.MSDS Overdose oral administration of ranolazine is observed as an increase in dizziness, nausea, and vomiting while intravenous administration can also produce diplopia, paresthesia, confusion, and syncope. In events of overdose, ECG monitoring is recommended.Label

Ranolazine was shown to lack genotoxic and carcinogenic potential. However, fertility studies reported an increased incidence of misshapen sternebrae and reduced ossification of pelvic and cranial bones.Label

Affected organisms
  • Humans and other mammals
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
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Ranolazine.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Ranolazine.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Ranolazine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Ranolazine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Ranolazine.
5-methoxy-N,N-dimethyltryptamineThe metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Ranolazine.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Ranolazine.
AbacavirRanolazine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Ranolazine.
AbexinostatThe risk or severity of QTc prolongation can be increased when Ranolazine is combined with Abexinostat.
Additional Data Available
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    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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Food Interactions
  • Grapefruit and grapefruit juice should be avoided throughout treatment.
  • Take without regard to meals.

References

Synthesis Reference
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. [PubMed:26979079]
  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. [PubMed:26459200]
  3. Reed M, Nicolas D: Ranolazine . [PubMed:29939605]
  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. [PubMed:29666676]
  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. [PubMed:25028555]
  6. Jerling M: Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-91. doi: 10.2165/00003088-200645050-00003. [PubMed:16640453]
  7. FDA approvals [Link]
  8. FDA approvals [Link]
  9. Australian Assessment Report [Link]
  10. RANEXA (ranolazine) Australian report [File]
External Links
Human Metabolome Database
HMDB0014388
PubChem Compound
56959
PubChem Substance
46505145
ChemSpider
51354
BindingDB
50173335
ChEBI
87690
ChEMBL
CHEMBL1404
Therapeutic Targets Database
DAP000875
PharmGKB
PA164746007
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ranolazine
ATC Codes
C01EB18 — Ranolazine
FDA label
Download (153 KB)
MSDS
Download (52.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableType 2 Diabetes Mellitus2
1CompletedOtherDrug-induced QT Interval Prolongation / Pharmacodynamics / Pharmacokinetics1
1CompletedTreatmentDrug-induced Surface ECG Changes1
1CompletedTreatmentMyotonia Congenita / Myotonia Congenita (Enrollment Complete) / Myotonic Dystrophy 1 / Paramyotonia Congenita1
1CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
1CompletedTreatmentType 2 Diabetes Mellitus1
1RecruitingTreatmentHealthy Male Individuals1
1TerminatedTreatmentSevere Renal Impairment1
2CompletedNot AvailableDiastolic Heart Failure1
2CompletedTreatmentAnginal Pain1
2CompletedTreatmentAtrial Fibrillation (AF)1
2CompletedTreatmentLong qt Syndrome1
2CompletedTreatmentMicrovascular Angina1
2CompletedTreatmentMyocardial Ischemia1
2CompletedTreatmentPersistent Atrial Fibrillation1
2CompletedTreatmentType 2 Diabetes Mellitus1
2RecruitingPreventionLong QT Syndrome Type 31
2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2RecruitingTreatmentHCM - Hypertrophic Non-Obstructive Cardiomyopathy1
2RecruitingTreatmentMyocardial Ischemia / Ventricular Premature Complexes1
2TerminatedNot AvailableAtherosclerotic Coronary Vascular Disease1
2TerminatedPreventionAcute Coronary Syndromes (ACS)1
2TerminatedTreatmentAnginal Pain1
2TerminatedTreatmentAtrial Fibrillation (AF) / Heart Failure1
2Unknown StatusTreatmentCongestive Cardiomyopathy1
2, 3CompletedTreatmentAcute Myocardial Ischemia / Coronary Artery Disease1
2, 3TerminatedTreatmentDiarrhoea Predominant Irritable Bowel Syndrome1
2, 3WithdrawnTreatmentAtrial Fibrillation (AF) / Recurrences1
3CompletedNot AvailableAnginal Pain / Coronary Artery Disease / Type 2 Diabetes Mellitus / Type I Diabetes1
3CompletedTreatmentAngina Pectoris / Coronary Artery Disease1
3CompletedTreatmentAnginal Pain1
3CompletedTreatmentAnginal Pain / Pulmonary Arterial Hypertension (PAH)1
3CompletedTreatmentHeart Failure / Ischaemic Cardiomyopathy / Nonischemic Cardiomyopathy1
3CompletedTreatmentMyocardial Ischemia1
3CompletedTreatmentArrhythmia of ventricular origin / Sudden Cardiac Death1
3CompletedTreatmentType 2 Diabetes Mellitus3
3Not Yet RecruitingPreventionCoronary Artery Disease1
3TerminatedTreatmentHeart; Dysfunction Postoperative, Cardiac Surgery1
3Unknown StatusTreatmentAtrial Fibrillation (AF)1
4CompletedNot AvailableChronic Angina1
4CompletedSupportive CareHypertrophic Cardiomyopathy1
4CompletedTreatmentAngina Pectoris / Coronary Artery Disease / Type 2 Diabetes Mellitus1
4CompletedTreatmentCardiovascular Heart Disease / End-Stage Renal Disease (ESRD)1
4CompletedTreatmentChest Pain / Dyspnea / Prophylaxis of cardiomyopathy1
4CompletedTreatmentChronic Stable Angina Pectoris1
4CompletedTreatmentDiastolic Left Ventricular Dysfunction / Pulmonary Hypertension (PH)1
4CompletedTreatmentMetabolic Syndromes / Stable Angina (SA)1
4CompletedTreatmentMicrovascular Angina1
4CompletedTreatmentMyocardial Ischemia / Myocardial Perfusion Imaging1
4CompletedTreatmentPulmonary Hypertension (PH)2
4Not Yet RecruitingPreventionMyocardial Stunning1
4Not Yet RecruitingTreatmentCoronary Artery Disease1
4RecruitingTreatmentAnginal Pain1
4TerminatedTreatmentCoronary Artery Disease / Pain / Peripheral Nervous System Diseases / Polyneuropathies1
4TerminatedTreatmentDiabetic Peripheral Neuropathic Pain (DPN)1
4Unknown StatusDiagnosticCoronary Artery Disease1
4Unknown StatusSupportive CareIschemic Mitral Regurgitation1
4Unknown StatusTreatmentAnginal Pain / Coronary Artery Disease / Metabolic Syndromes1
4Unknown StatusTreatmentAtrial Fibrillation (AF) / Chronic Stable Angina Pectoris / Coronary Artery Disease / Ventricular Tachycardia (VT)1
4Unknown StatusTreatmentIschemic Heart Disease1
4Unknown StatusTreatmentPremature Ventricular Beats1
4WithdrawnTreatmentAngina Pectoris / Coronary Artery Disease / Type 2 Diabetes Mellitus1
4WithdrawnTreatmentAnginal Pain / Peripheral Arterial Disease (PAD)1
4WithdrawnTreatmentArteriosclerosis / Chronic Stable Angina Pectoris / Coronary Artery Disease / Myocardial Ischemia1
Not AvailableCompletedNot AvailableArrhythmia1
Not AvailableCompletedDiagnosticAdenocarcinoma of the Prostate / Bone Metastases / Soft Tissue Metastases / Stage IIA Prostate Cancer / Stage IIB Prostate Cancer / Stage III Prostate Cancer / Stage IV Prostate Cancer1
Not AvailableCompletedPreventionAtrial Fibrillation New Onset / Hemorrhage / Medical Care; Complications, Late Effect of Complications / Prolonged QT Interval / Ventricular Tachycardia (VT)1
Not AvailableCompletedTreatmentAnginal Pain1
Not AvailableCompletedTreatmentMicrovascular Coronary Dysfunction (MCD)1
Not AvailableCompletedTreatmentPeripheral Arterial Disease (PAD)1
Not AvailableRecruitingTreatmentCoronary Artery Disease / Coronary Microcirculation / Ischaemia / Myocardial Diseases1
Not AvailableTerminatedSupportive CareProphylaxis of cardiomyopathy1
Not AvailableTerminatedTreatmentDiastolic Heart Failure / Echocardiography / Ranolazine / Tissue Doppler Ultrasound1
Not AvailableUnknown StatusNot AvailableAnginal Pain / Heart Diseases1
Not AvailableUnknown StatusTreatmentHeart Failure With Preserved Ejection Fraction (HFpEF)1
Not AvailableWithdrawnNot AvailableIschaemic Myocardial Dysfunction / Severe Coronary Artery Disease1
Not AvailableWithdrawnOtherSilent Myocardial Ischemia / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
  • Gilead sciences inc
Packagers
  • Atlantic Biologicals Corporation
  • DSM Corp.
  • Gilead Sciences Inc.
Dosage forms
FormRouteStrength
Tablet, film coated, extended releaseOral1000 mg/1
Tablet, film coated, extended releaseOral500 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)
US6303607No2001-10-162019-05-27Us
US6479496No2002-11-122019-05-27Us
US6525057No2003-02-252019-05-27Us
US6562826No2003-05-132019-05-27Us
US6620814No2003-09-162019-05-27Us
US6852724No2005-02-082019-05-27Us
US6864258No2005-03-082019-05-27Us
US6617328No2003-09-092019-05-27Us
US6369062No2002-04-092019-05-27Us
US6503911No2003-01-072019-05-27Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)120-124 ºC'MSDS'
boiling point (°C)624.1 ºC at 760 mmHgLookChem
water solubility<1 mg/ml'MSDS'
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

Taxonomy

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
Phenoxy compound / Anisole / M-xylene / Xylene / Methoxybenzene / Alkyl aryl ether / N-alkylpiperazine / Monocyclic benzene moiety / 1,4-diazinane / Piperazine
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
monocarboxylic acid amide, secondary alcohol, aromatic amide, N-alkylpiperazine, monomethoxybenzene (CHEBI:87690)

Targets

Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. [PubMed:26979079]
  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. [PubMed:26459200]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
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. [PubMed:26459200]
Kind
Protein group
Organism
Humans
Pharmacological action
No
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. [PubMed:26459200]
  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. [PubMed:23472826]
  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. [PubMed:16520744]
  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. [PubMed:26185330]
Kind
Protein group
Organism
Humans
Pharmacological action
No
Actions
Antagonist
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. [PubMed:26979079]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
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. [PubMed:26979079]
6. Fatty acid
Kind
Group
Organism
Not Available
Pharmacological action
No
Actions
Other/unknown
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. [PubMed:26979079]

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. [PubMed:26979079]
  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. [PubMed:25028555]
  3. Australian Assessment Report [Link]
  4. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [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. [PubMed:26979079]
  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. [PubMed:25028555]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. 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. [PubMed:29666676]
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. [PubMed:16717165]
  2. RANEXA (ranolazine) Australian report [File]

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. [PubMed:24014644]
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. [PubMed:26459200]
  2. Reed M, Nicolas D: Ranolazine . [PubMed:29939605]
  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. [PubMed:25028555]

Drug created on June 13, 2005 07:24 / Updated on December 02, 2019 05:19