Identification
NameRegadenoson
Accession NumberDB06213
TypeSmall Molecule
GroupsApproved
Description

Regadenoson is an A2A adenosine receptor agonist that causes coronary vasodilation and used for myocardial perfusion imagining. Manufactured by Astellas and FDA approved April 10, 2008.

Structure
Thumb
Synonyms
Regadenoson anhydrous
External IDs CVT-3146
Product Ingredients
IngredientUNIICASInChI KeyDetails
Regadenoson monohydrate2XLN4Y044H 875148-45-1CDQVVPUXSPZONN-WPPLYIOHSA-NDetails
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LexiscanInjection, solution.08 mg/mLIntravenousAstellas Pharma Inc2008-04-10Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNII7AXV542LZ4
CAS number313348-27-5
WeightAverage: 390.354
Monoisotopic: 390.140015726
Chemical FormulaC15H18N8O5
InChI KeyLZPZPHGJDAGEJZ-AKAIJSEGSA-N
InChI
InChI=1S/C15H18N8O5/c1-17-13(27)6-2-19-23(3-6)15-20-11(16)8-12(21-15)22(5-18-8)14-10(26)9(25)7(4-24)28-14/h2-3,5,7,9-10,14,24-26H,4H2,1H3,(H,17,27)(H2,16,20,21)/t7-,9-,10-,14-/m1/s1
IUPAC Name
1-{6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-9H-purin-2-yl}-N-methyl-1H-pyrazole-4-carboxamide
SMILES
CNC(=O)C1=CN(N=C1)C1=NC2=C(N=CN2[C@@H]2O[[email protected]](CO)[C@@H](O)[[email protected]]2O)C(N)=N1
Pharmacology
Indication

Diagnostic agent for radionuclide myocardial perfusion imaging (MPI)

Structured Indications Not Available
Pharmacodynamics

Regadenoson rapidly increases coronary blood flow (CBF) which is sustained for a short duration. Mean average peak velocity increased to greater than twice baseline by 30 seconds and decreased to less than twice the baseline level within 10 minutes. Myocardial uptake of the radiopharmaceutical is proportional to (CBF). Regadenoson increases blood flow in normal coronary arteries but not in stenotic (blocked) arteries. The significance of this finding is that stenotic arteries will take up less of the radiopharmaceutical than normal coronary arteries, resulting in a signal that is less intense in these areas.

Mechanism of action

Regadenoson is an selective low-affinity (Ki= 1.3 µM) A2A receptor agonist that mimics the effects of adenosine in causing coronary vasodilatation and increasing myocardial blood flow. It is a very weak agonist of the A1 adenosine receptor (Ki > 16.5 µM). Furthermore, it has negligible affinity to A2B and A3 adenosine receptors. Regadenoson is undergoing trials for use in pharmacological stress tests. Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the A-V node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome.

TargetKindPharmacological actionActionsOrganismUniProt ID
Adenosine receptor A2aProteinyes
agonist
HumanP29274 details
Related Articles
Absorption

The pharmacokinetic profile of regadenoson is best described by a 3-compartment model. T max, injection = 1 to 3 minutes; Onset of pharmacodynamic response = 1 to 3 minutes;
E max 12.3 ng/mL

Volume of distribution

Central compartment: 11.5 L; Steady state: 78.7 L

Protein bindingNot Available
Metabolism

The metabolism of regadenoson is unknown in humans. The cytochrome P450 enzyme system is not likely to be involved with the metabolism of regadenoson.

Route of elimination

58% of total regadenoson eliminate is via renal excretion

Half life

Initial phase: 2-4 minutes; Intermediate phase: 30 minutes (this phase coincides with a loss of the pharmacodynamic effect); Terminal phase: 2 hours

Clearance

Average plasma renal clearance = 450 mL/min. As this value is larger than the glomerular filtration rate, this suggests occurrence of renal tubular secretion.

Toxicity

The most common (incidence ≥ 5%) adverse reactions to regadenoson are dyspnea, headache, flushing, chest discomfort, dizziness, angina pectoris, chest pain, and nausea. MTD (male, supine position): 20 µg/kg; MTD (male, standing position): 10 µg/kg;

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
AminophyllineAminophylline may decrease the vasodilatory activities of Regadenoson.Approved
CaffeineCaffeine may decrease the vasodilatory activities of Regadenoson.Approved
DipyridamoleThe risk or severity of adverse effects can be increased when Dipyridamole is combined with Regadenoson.Approved
TheophyllineTheophylline may decrease the vasodilatory activities of Regadenoson.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Mitka M: New stress test agents reduce adverse effects. JAMA. 2008 May 14;299(18):2140. doi: 10.1001/jama.299.18.2140. [PubMed:18477777 ]
  2. Lieu HD, Shryock JC, von Mering GO, Gordi T, Blackburn B, Olmsted AW, Belardinelli L, Kerensky RA: Regadenoson, a selective A2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl Cardiol. 2007 Jul;14(4):514-20. [PubMed:17679059 ]
  3. Zoghbi GJ, Iskandrian AE: Selective adenosine agonists and myocardial perfusion imaging. J Nucl Cardiol. 2012 Feb;19(1):126-41. doi: 10.1007/s12350-011-9474-9. [PubMed:22130964 ]
External Links
ATC CodesC01EB21 — Regadenoson
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (176 KB)
MSDSDownload (479 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedDiagnosticIschaemic Heart Diseases1
0RecruitingDiagnosticBlood Brain Barrier Defect1
1CompletedNot AvailableHealthy Volunteers1
1CompletedDiagnosticCoronary Artery Disease1
1CompletedTreatmentSickle Cell Disorders1
1Not Yet RecruitingTreatmentLung Transplant1
2CompletedDiagnosticCoronary Artery Disease1
2CompletedDiagnosticCoronary Artery Disease / Nonvalvular Atrial Fibrillation1
2CompletedDiagnosticMyocardial Ischemia1
2RecruitingBasic ScienceRetinal Artery Occlusions1
2RecruitingDiagnosticCardiovascular Disease (CVD) / Coronary Artery Disease1
2RecruitingTreatmentSickle Cell Disorders1
2TerminatedDiagnosticCoronary Artery Disease / Heart Diseases1
2WithdrawnDiagnosticCoronary Artery Disease1
3CompletedNot AvailableCoronary Artery Disease1
3CompletedDiagnosticCoronary Artery Disease3
4CompletedDiagnosticAcute Graft Rejection / Cardiac Transplant / Chronic Graft Rejection1
4CompletedDiagnosticAsthma Bronchial / Coronary Artery Disease / Pulmonary Disease, Chronic Obstructive1
4CompletedDiagnosticCoronary Artery Disease1
4CompletedDiagnosticCoronary Artery Disease / Diabetes, Diabetes Mellitus Type 11
4CompletedDiagnosticCoronary Artery Disease / Kidney Diseases1
4CompletedDiagnosticIschaemic Heart Diseases1
4CompletedDiagnosticMyocardial Blood Flow Reserve1
4RecruitingDiagnosticCoronary Artery Disease2
4RecruitingDiagnosticDiastolic Heart Failure / Heart Failure, Diastolic / Heart Failure, Left-Sided / Hypertensive1
4RecruitingDiagnosticTransient ischemia attacks1
4TerminatedDiagnosticAnginal Pain / Asthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD) / Coronary Artery Disease1
Not AvailableCompletedNot AvailableCoronary Artery Disease / Type 2 Diabetes Mellitus1
Not AvailableCompletedDiagnosticBMI >30 kg/m2 / Decreased Vascular Flow / Endothelial Dysfunction1
Not AvailableCompletedDiagnosticCardiac Function1
Not AvailableCompletedDiagnosticCoronary Artery Disease2
Not AvailableCompletedDiagnosticCoronary Artery Disease / Myocardial Ischemia1
Not AvailableCompletedDiagnosticCoronary Artery Disease / Myocardial Perfusion Abnormalities1
Not AvailableCompletedDiagnosticCoronary Heart Disease (CHD)1
Not AvailableEnrolling by InvitationDiagnosticLeft Ventricular Systolic Dysfunction / Sudden Cardiac Death1
Not AvailableNot Yet RecruitingTreatmentPulmonary Hypertension (PH)1
Not AvailableRecruitingNot AvailableCoronary Artery Disease1
Not AvailableRecruitingNot AvailableCoronary Artery Disease / Coronary Microvascular Disease1
Not AvailableRecruitingBasic ScienceCAD / Coronary Artery Disease1
Not AvailableRecruitingDiagnosticCoronary Artery Disease1
Not AvailableRecruitingDiagnosticCoronary Heart Disease (CHD)1
Not AvailableRecruitingDiagnosticSickle Cell Disorders1
Not AvailableRecruitingHealth Services ResearchMRI Scans1
Not AvailableUnknown StatusDiagnosticCoronary Artery Disease / Myocardial Perfusion Abnormalities1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous.08 mg/mL
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6403567 No2002-04-102022-04-10Us
US6642210 No1999-06-222019-06-22Us
US7144872 No1999-06-222019-06-22Us
US7183264 No1999-06-222019-06-22Us
US7582617 No1999-06-222019-06-22Us
US7655636 No1999-06-222019-06-22Us
US7655637 No1999-06-222019-06-22Us
US7683037 No1999-06-222019-06-22Us
US8106029 No1999-06-222019-06-22Us
US8106183 No2007-02-022027-02-02Us
US8133879 No1999-06-222019-06-22Us
US8183226 No1999-06-222019-06-22Us
US8470801 No1999-06-222019-06-22Us
US8536150 No1999-06-222019-06-22Us
US9045519 No1999-06-222019-06-22Us
US9085601 No2007-02-022027-02-02Us
US9289446 No1999-06-222019-06-22Us
Properties
StateLiquid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.85 mg/mLALOGPS
logP-0.89ALOGPS
logP-2.3ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)12.37ChemAxon
pKa (Strongest Basic)1.63ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area186.46 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity95.48 m3·mol-1ChemAxon
Polarizability37.48 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.7551
Caco-2 permeable-0.7753
P-glycoprotein substrateNon-substrate0.6036
P-glycoprotein inhibitor INon-inhibitor0.9328
P-glycoprotein inhibitor IINon-inhibitor0.9762
Renal organic cation transporterNon-inhibitor0.9423
CYP450 2C9 substrateNon-substrate0.8795
CYP450 2D6 substrateNon-substrate0.8433
CYP450 3A4 substrateSubstrate0.5052
CYP450 1A2 substrateNon-inhibitor0.8108
CYP450 2C9 inhibitorNon-inhibitor0.9275
CYP450 2D6 inhibitorNon-inhibitor0.9568
CYP450 2C19 inhibitorNon-inhibitor0.9373
CYP450 3A4 inhibitorNon-inhibitor0.9626
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9931
Ames testNon AMES toxic0.6997
CarcinogenicityNon-carcinogens0.8987
BiodegradationNot ready biodegradable0.9669
Rat acute toxicity2.2022 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.964
hERG inhibition (predictor II)Non-inhibitor0.8999
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as purine nucleosides. These are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety.
KingdomChemical entities
Super ClassOrganic compounds
ClassNucleosides, nucleotides, and analogues
Sub ClassPurine nucleosides
Direct ParentPurine nucleosides
Alternative ParentsGlycosylamines / 6-aminopurines / Pentoses / Pyrazole-4-carboxamides / Aminopyrimidines and derivatives / Primary aromatic amines / Imidolactams / N-substituted imidazoles / Vinylogous amides / Heteroaromatic compounds
SubstituentsPurine nucleoside / Glycosyl compound / N-glycosyl compound / 6-aminopurine / Pentose monosaccharide / Imidazopyrimidine / Purine / Pyrazole-4-carboxamide / Aminopyrimidine / N-substituted imidazole
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Identical protein binding
Specific Function:
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
ADORA2A
Uniprot ID:
P29274
Uniprot Name:
Adenosine receptor A2a
Molecular Weight:
44706.925 Da
References
  1. Zoghbi GJ, Iskandrian AE: Selective adenosine agonists and myocardial perfusion imaging. J Nucl Cardiol. 2012 Feb;19(1):126-41. doi: 10.1007/s12350-011-9474-9. [PubMed:22130964 ]
Drug created on March 19, 2008 10:17 / Updated on July 27, 2017 16:03