Identification

Name
Regadenoson
Accession Number
DB06213
Type
Small Molecule
Groups
Approved, Investigational
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
  • Regadenoson anhydrous
External IDs
CVT-3146
Product Ingredients
IngredientUNIICASInChI Key
Regadenoson monohydrate2XLN4Y044H875148-45-1CDQVVPUXSPZONN-WPPLYIOHSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LexiscanInjection, solution0.08 mg/1mLIntravenousAstellas Pharma Inc2008-04-10Not applicableUs
Categories
UNII
7AXV542LZ4
CAS number
313348-27-5
Weight
Average: 390.354
Monoisotopic: 390.140015726
Chemical Formula
C15H18N8O5
InChI Key
LZPZPHGJDAGEJZ-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[C@H](CO)[C@@H](O)[C@H]2O)C(N)=N1

Pharmacology

Indication

Diagnostic agent for radionuclide myocardial perfusion imaging (MPI)

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.

TargetActionsOrganism
AAdenosine receptor A2a
agonist
Human
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 binding
Not 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
3-isobutyl-1-methyl-7H-xanthine3-isobutyl-1-methyl-7H-xanthine may decrease the vasodilatory activities of Regadenoson.
6-O-benzylguanine6-O-benzylguanine may decrease the vasodilatory activities of Regadenoson.
7-Deazaguanine7-Deazaguanine may decrease the vasodilatory activities of Regadenoson.
7,9-Dimethylguanine7,9-Dimethylguanine may decrease the vasodilatory activities of Regadenoson.
8-azaguanine8-azaguanine may decrease the vasodilatory activities of Regadenoson.
8-chlorotheophylline8-chlorotheophylline may decrease the vasodilatory activities of Regadenoson.
9-Deazaguanine9-Deazaguanine may decrease the vasodilatory activities of Regadenoson.
9-Methylguanine9-Methylguanine may decrease the vasodilatory activities of Regadenoson.
AcefyllineAcefylline may decrease the vasodilatory activities of Regadenoson.
AminophyllineAminophylline may decrease the vasodilatory activities of Regadenoson.
Food Interactions
Not Available

References

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
KEGG Drug
D05711
PubChem Compound
219024
PubChem Substance
175427061
ChemSpider
189859
BindingDB
50119132
ChEBI
135613
ChEMBL
CHEMBL317052
PharmGKB
PA166129536
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Regadenoson
ATC Codes
C01EB21 — Regadenoson
FDA label
Download (176 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedDiagnosticBlood Brain Barrier Defect1
0CompletedDiagnosticIschaemic Heart Diseases1
0TerminatedDiagnosticAnginal Pain / Asthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD) / Coronary Artery Disease1
1Active Not RecruitingDiagnosticHeart Diseases1
1CompletedNot AvailableHealthy Volunteers1
1CompletedDiagnosticCoronary Artery Disease1
1CompletedTreatmentSickle Cell Disorders1
1RecruitingTreatmentLung Transplant1
2CompletedDiagnosticCardiovascular Disease (CVD) / Coronary Artery Disease1
2CompletedDiagnosticCoronary Artery Disease1
2CompletedDiagnosticCoronary Artery Disease / Nonvalvular Atrial Fibrillation1
2CompletedDiagnosticMyocardial Ischemia1
2CompletedTreatmentSickle Cell Disorders1
2RecruitingBasic ScienceRetinal Artery Occlusions1
2TerminatedDiagnosticCoronary Artery Disease / Heart Diseases1
2TerminatedTreatmentMicrovascular coronary artery disease1
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 Disease2
4CompletedDiagnosticCoronary Artery Disease / Diabetes, Diabetes Mellitus Type 11
4CompletedDiagnosticCoronary Artery Disease / Kidney Diseases1
4CompletedDiagnosticIschaemic Heart Diseases1
4CompletedDiagnosticMyocardial Blood Flow Reserve1
4Not Yet RecruitingDiagnosticHeart Transplant Failure and Rejection1
4RecruitingBasic ScienceHypertrophic Cardiomyopathy / Microvascular Ischaemia of Myocardium / Non-ischemic Dilated Cardiomyopathy1
4RecruitingDiagnosticCoronary Artery Disease1
4RecruitingDiagnosticDiastolic Heart Failure / Heart Failure, Diastolic / Heart Failure, Left-Sided / High Blood Pressure (Hypertension)1
4RecruitingDiagnosticTransient ischemia attacks1
Not AvailableActive Not RecruitingDiagnosticSickle Cell Disorders1
Not AvailableCompletedNot AvailableCoronary Artery Disease / Type 2 Diabetes Mellitus1
Not AvailableCompletedBasic ScienceCoronary Artery Disease1
Not AvailableCompletedDiagnosticBMI >30 kg/m2 / Decreased Vascular Flow / Endothelial Dysfunction1
Not AvailableCompletedDiagnosticCardiac Function1
Not AvailableCompletedDiagnosticCoronary Artery Disease3
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 AvailableRecruitingNot AvailableAnatomic Stage I Breast Cancer AJCC v8 / Anatomic Stage IA Breast Cancer AJCC v8 / Anatomic Stage IB Breast Cancer AJCC v8 / Anatomic Stage II Breast Cancer AJCC v8 / Anatomic Stage IIA Breast Cancer AJCC v8 / Anatomic Stage IIB Breast Cancer AJCC v8 / Anatomic Stage III Breast Cancer AJCC v8 / Anatomic Stage IIIA Breast Cancer AJCC v8 / Anatomic Stage IIIB Breast Cancer AJCC v8 / Anatomic Stage IIIC Breast Cancer AJCC v8 / Premenopausal / Prognostic Stage I Breast Cancer AJCC v8 / Prognostic Stage IA Breast Cancer AJCC v8 / Prognostic Stage IB Breast Cancer AJCC v8 / Prognostic Stage II Breast Cancer AJCC v8 / Prognostic Stage IIA Breast Cancer AJCC v8 / Prognostic Stage IIB Breast Cancer AJCC v8 / Prognostic Stage III Breast Cancer AJCC v8 / Prognostic Stage IIIA Breast Cancer AJCC v8 / Prognostic Stage IIIB Breast Cancer AJCC v8 / Prognostic Stage IIIC Breast Cancer AJCC v81
Not AvailableRecruitingNot AvailableCoronary Artery Disease2
Not AvailableRecruitingNot AvailableCoronary Artery Disease / Coronary Microvascular Disease1
Not AvailableRecruitingDiagnosticCoronary Heart Disease (CHD)1
Not AvailableRecruitingHealth Services ResearchMRI Scans1
Not AvailableTerminatedTreatmentPulmonary Hypertension (PH)1
Not AvailableUnknown StatusDiagnosticCoronary Artery Disease / Myocardial Perfusion Abnormalities1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionIntravenous0.08 mg/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6403567No2002-06-112022-04-10Us
US6642210No2003-11-042019-06-22Us
US7144872No2006-12-052019-06-22Us
US7183264No2007-02-272019-06-22Us
US7582617No2009-09-012019-06-22Us
US7655636No2010-02-022019-06-22Us
US7655637No2010-02-022019-06-22Us
US7683037No2010-03-232019-06-22Us
US8106029No2012-01-312019-06-22Us
US8183226No2012-05-222019-06-22Us
US8536150No2013-09-172019-06-22Us
US8470801No2013-06-252019-06-22Us
US9289446No2016-03-222019-06-22Us
US8106183No2012-01-312027-02-02Us
US8133879No2012-03-132019-06-22Us
US9085601No2015-07-212027-02-02Us
US9045519No2015-06-022019-06-22Us

Properties

State
Liquid
Experimental Properties
Not 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
SpectrumSpectrum TypeSplash Key
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as purine nucleosides. These are compounds comprising a purine base attached to a ribosyl or deoxyribosyl moiety.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Purine nucleosides
Sub Class
Not Available
Direct Parent
Purine nucleosides
Alternative Parents
Glycosylamines / 6-aminopurines / Pentoses / Pyrazole-4-carboxamides / Aminopyrimidines and derivatives / Imidolactams / N-substituted imidazoles / Vinylogous amides / Tetrahydrofurans / Heteroaromatic compounds
show 10 more
Substituents
Purine nucleoside / Glycosyl compound / N-glycosyl compound / 6-aminopurine / Pentose monosaccharide / Imidazopyrimidine / Purine / Pyrazole-4-carboxamide / Aminopyrimidine / Monosaccharide
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Details
1. Adenosine receptor A2a
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 December 14, 2018 16:28