A2AR ( Ki = 290 nM )

Regadenoson exhibits a comparatively low binding affinity (hA2A Ki=290 nM) for human A2A receptors, along with a selectivity that is over 30-fold greater than that of the A2B and A3AR subtypes, and 13-fold greater than that of the A1AR. While regadenoson acts as a full and strong agonist to cause coronary vasodilation, it acts as a weak partial agonist to cause cAMP accumulation in PC12 cells[1].

Intravenous bolus injection of regadenoson results in a dose-dependent decrease in coronary vascular resistance and an increase in myocardial blood flow in a dog model. Regadenoson was demonstrated to cause a dose-dependent rise in heart rate and a drop in mean arterial pressure at higher dosages in a rat heart model. Additionally, serum norepinephrine and epinephrine increased by more than two times when regadenoson was administered. According to clinical data, regadenoson has an estimated clearance of 37.8 L/h and a volume of distribution of 11.5 L and 78.7 L (at steady-state). Its renal excretion accounts for 58% of its total elimination, and its terminal half-life ranges from 33 to 108 minutes[2].

Mongrel dogs (23-27 kg)
0.1, 0.175, 0.25, 0.5, 1.0, 2.5, 5 µg/kg
Peripheral intravenous injection; single

Absorption, Distribution and Excretion
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
58% of total regadenoson eliminate is via renal excretion
Central compartment: 11.5 L; Steady state: 78.7 L
Average plasma renal clearance = 450 mL/min. As this value is larger than the glomerular filtration rate, this suggests occurrence of renal tubular secretion.

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

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Biological 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

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of regadenoson during breastfeeding. To avoid exposure of the infant to regadenoson, nursing mothers should avoid breastfeeding for 10 hours after drug administration.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. J Med Chem . 2014 May 8;57(9):3623-50.

[2]. J Am Coll Cardiol . 2009 Sep 22;54(13):1123-30.

Regadenoson is a purine nucleoside.
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.
Regadenoson anhydrous is a Pharmacologic Cardiac Stress Test Agent. The mechanism of action of regadenoson anhydrous is as an Adenosine Receptor Agonist.
Regadenoson is an adenosine derivative and selective A2A adenosine receptor agonist with coronary vasodilating activity. Upon administration, regadenoson selectively binds to and activates the A2A adenosine receptor, which induces coronary vasodilation. This leads to an increase in coronary blood flow and enhances myocardial perfusion. Compared to adenosine, regadenoson has a longer half-life and shows higher selectivity towards the A2A adenosine receptor. This agent is a very weak agonist for the A1 adenosine receptor and has negligible affinity for the A2B and A3 adenosine receptors.

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Drug Indication
Diagnostic agent for radionuclide myocardial perfusion imaging (MPI)
FDA Label
This medicinal product is for diagnostic use only. Rapiscan is a selective coronary vasodilator for use as a pharmacological stress agent for radionuclide myocardial perfusion imaging (MPI) in adult patients unable to undergo adequate exercise stress.
Diagnosis of myocardial perfusion disturbances

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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.

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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.

C15H18N8O5

390.35402

390.14

C, 46.15; H, 4.65; N, 28.71; O, 20.49

313348-27-5

Regadenoson-d3; 313348-27-5 (free); 875148-45-1 (hydrate)

219024

Solid powder

2.0±0.1 g/cm3

158-160ºC

1.896

-3.09

5

10

4

28

587

4

OC[C@@H]1[C@H]([C@H]([C@H](N2C=NC3=C2N=C(N4N=CC(C(NC)=O)=C4)N=C3N)O1)O)O

LZPZPHGJDAGEJZ-AKAIJSEGSA-N

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

1-[6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-methylpyrazole-4-carboxamide

CVT-3146; CVT 3146; CVT3146; Lexiscan

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: 50~78 mg/mL (128.1~199.8 mM)
Ethanol: ~2 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)