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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:21 UTC
HMDB IDHMDB14388
Secondary Accession NumbersNone
Metabolite Identification
Common NameRanolazine
DescriptionRanolazine is only found in individuals that have used or taken this drug. It is an antianginal medication. On January 31, 2006, ranolazine was approved for use in the United States by the FDA for the treatment of chronic angina. [Wikipedia]The mechanism of action of ranolazine is unknown. It does not increase the rate-pressure product, a measure of myocardial work, at maximal exercise. In vitro studies suggest that ranolazine is a P-gp inhibitor. Ranolazine is believed to have its effects via altering the trans-cellular late sodium current. It is by altering the intracellular sodium level that ranolazine affects the sodium-dependent calcium channels during myocardial ischemia. Thus, ranolazine indirectly prevents the calcium overload that causes cardiac ischemia.
Structure
Thumb
Synonyms
ValueSource
RanexaKegg
(-)-RanolazineHMDB
Ranolazine 2HCLHMDB
Chemical FormulaC24H33N3O4
Average Molecular Weight427.5365
Monoisotopic Molecular Weight427.247106559
IUPAC NameN-(2,6-dimethylphenyl)-2-{4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl}acetamide
Traditional Nameranolazine
CAS Registry Number142387-99-3
SMILES
COC1=CC=CC=C1OCC(O)CN1CCN(CC(=O)NC2=C(C)C=CC=C2C)CC1
InChI Identifier
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)
InChI KeyInChIKey=XKLMZUWKNUAPSZ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • N-arylamide
  • N-piperazineacetamide
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • N-alkylpiperazine
  • Alkyl aryl ether
  • Benzenoid
  • Piperazine
  • 1,4-diazinane
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxamide group
  • 1,2-aminoalcohol
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Enzyme Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.10e-01 g/LNot Available
LogP1.6Not Available
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00243
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00243
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00243
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID51354
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkRanolazine
NuGOwiki LinkHMDB14388
Metagene LinkHMDB14388
METLIN IDNot Available
PubChem Compound56959
PDB IDNot Available
ChEBI ID441382
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Hale SL, Kloner RA: Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55. [17220471 ]
  2. Chaitman BR, Pepine CJ, Parker JO, Skopal J, Chumakova G, Kuch J, Wang W, Skettino SL, Wolff AA: Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):309-16. [14734593 ]
  3. Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L: Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006 Aug 1;48(3):566-75. Epub 2006 Jun 15. [16875985 ]
  4. Fraser H, Belardinelli L, Wang L, Light PE, McVeigh JJ, Clanachan AS: Ranolazine decreases diastolic calcium accumulation caused by ATX-II or ischemia in rat hearts. J Mol Cell Cardiol. 2006 Dec;41(6):1031-8. Epub 2006 Oct 5. [17027025 ]
  5. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E: Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007 Apr 25;297(16):1775-83. [17456819 ]

Enzymes

General function:
Involved in monooxygenase 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
General function:
Involved in ion channel activity
Specific function:
This protein 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 sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular weight:
226937.5
References
  1. Hale SL, Kloner RA: Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic myocardial dysfunction in the rabbit. J Cardiovasc Pharmacol Ther. 2006 Dec;11(4):249-55. [17220471 ]
  2. Rajamani S, Shryock JC, Belardinelli L: Block of tetrodotoxin-sensitive, Na(V)1.7 and tetrodotoxin-resistant, Na(V)1.8, Na+ channels by ranolazine. Channels (Austin). 2008 Nov-Dec;2(6):449-60. Epub 2008 Nov 7. [19077543 ]
General function:
Involved in ion 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 sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular weight:
226340.1
References
  1. Rajamani S, Shryock JC, Belardinelli L: Block of tetrodotoxin-sensitive, Na(V)1.7 and tetrodotoxin-resistant, Na(V)1.8, Na+ channels by ranolazine. Channels (Austin). 2008 Nov-Dec;2(6):449-60. Epub 2008 Nov 7. [19077543 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]