Regadenoson

Product Overview

Regadenoson (development code CVT-3146) was developed by CV Therapeutics, approved by the US FDA in April 2008, and marketed by Astellas as Lexiscan. It is the first adenosine A2A receptor agonist proven safe and effective as a pharmacologic stress agent for myocardial perfusion imaging (MPI).

The key to its structural design: Built on an adenosine (purine nucleoside) core, with an N-methylpyrazole-4-carboxamide substituent introduced at the 2-position of the purine ring. This modification reduces affinity for adenosine A1 and A3 receptors; radioligand binding assays show more than 10-fold selectivity for A2A over the A1 and A3 subtypes — this is precisely the structural basis for preserving coronary vasodilation while reducing adverse reactions such as atrioventricular block, and the core distinction from non-selective adenosine (which activates A1, A2A, A2B and A3 simultaneously).

Pharmacology and pharmacodynamics: Selective A2A receptor agonism dilates the coronary arteries; in an open-chest anesthetized pig model it increased coronary blood flow 3.4–3.8 fold, with a reversal half-life of only 1.9–2.6 minutes — rapid and short-lived action, convenient for completing the procedure within the imaging window. Administered as a fixed 0.4 mg rapid (approx. 10-second) intravenous bolus with no weight-based dose adjustment — a major operational advantage over adenosine infusion (which requires weight-based calculation and continuous infusion).

Clinical comparison: Compared with adenosine stress MPI, qualitative and quantitative image metrics showed no significant differences; total adverse reactions with regadenoson were significantly fewer (P=0.015), and subject tolerability was superior to adenosine (P=0.001). Its safety and efficacy have been demonstrated across sex, age, body mass index and in patients with diabetes.

Technical Specifications

• Standards: CHP / USP / EP
• Specification: 0.99 (purity ≥99.0%, HPLC); reagents / reference standards commonly 98.0%–99.83%
• CAS No.: 313348-27-5 (anhydrous / free form; FDA UNII 7AXV542LZ4; ATC C01EB21; PubChem CID 219024); monohydrate CAS 875148-45-1
• Molecular formula: C₁₅H₁₈N₈O₅; monohydrate C₁₅H₁₈N₈O₅·H₂O
• Molecular weight: 390.35 (Cayman records 390.4); monohydrate 408.37 (Chinese injection labeling is expressed as the monohydrate); exact mass 390.1400
• Appearance: White to off-white / grayish-white to light brown crystalline solid or powder (Cayman records a crystalline solid; most suppliers describe a grayish-white to light brown solid; other sources record “white to beige”)
• Purity (HPLC): ≥ 99.0%
• Melting point: 158–160 °C (consistent across ChemicalBook, InvivoChem, Xiyu Reagent and other sources — recommended). Other sources record approximately 194–196 °C, of lower authority and markedly different — for reference only — the two values differ significantly; the source must be cited when adopting either
• Specific rotation: No official specific rotation is recorded in pharmacopoeias or authoritative standards; the molecule contains 4 defined stereocenters (the 2′, 3′, 4′ and 1′ positions of the ribofuranose, all in the β-D-ribofuranose configuration), and quality control is typically performed by chiral HPLC / enantiomeric purity and structural confirmation (NMR, MS) instead
• Chemical name: 1-[6-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]purin-2-yl]-N-methyl-1H-pyrazole-4-carboxamide; also known as 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]adenosine
• Stereochemistry: 4 defined stereocenters; a β-D-ribofuranoside
• Solubility: Practically insoluble in water; freely soluble in DMSO (sources vary widely: ≥5 mg/mL, 14 mg/mL, 50 mg/mL, 78 mg/mL, depending on DMSO water content and sonication); slightly soluble in methanol, ethanol (approx. 2 mg/mL) and DMF (10 mg/mL). Due to extremely poor water solubility, the marketed injection uses 15% (w/w, 150 mg/mL) propylene glycol as a solubilizer
• UV absorption (λmax): 247, 271 nm
• Acidity coefficient (pKa): 13.07 ± 0.70 (calculated)
• Computed physicochemical parameters: Density approx. 1.98–2.0 g/cm³; refractive index 1.896; LogP −3.09; H-bond donors 5 / acceptors 10; rotatable bonds 4; topological polar surface area approx. 186.5 Ų; heavy atom count 28
• Storage: Protected from light, sealed and dry, at 2–8 °C (powder keeps 2 years at 2–8 °C, 3 years at −20 °C); some reference standards recommend −20 °C under inert gas; solutions should be aliquoted and stored 6 months at −80 °C or 1 month at −20 °C, avoiding repeated freeze–thaw cycles

Applications

• Pharmacologic stress for radionuclide myocardial perfusion imaging (MPI) (core indication): As a pharmacologic stress agent for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress, to evaluate myocardial ischemia and coronary artery disease. Administered as a 0.4 mg rapid (≤10-second) intravenous bolus with no weight-based dose adjustment; the bolus is immediately followed by a saline flush, then injection of the radionuclide imaging agent
• Approval status in China: Regadenoson injection (brand name Hainuosheng, Nanjing Hairong Pharmaceutical, approval number Guoyao Zhunzi H20213800) is the stress agent approved in China for the diagnosis of myocardial ischemia by radionuclide myocardial perfusion imaging; strength 5 mL:0.4 mg (expressed as C₁₅H₁₈N₈O₅); a colorless, clear liquid; store sealed at no more than 25 °C
• Marketed formulation highlights: The marketed injection contains propylene glycol (150 mg/mL, solubilizer), dibasic sodium phosphate and monobasic sodium phosphate (buffer, pH 6.3–7.7), and edetate disodium (chelating agent); preservative-free; single-dose 5 mL vial or prefilled syringe
• Pre-dose preparation (important): Patients should be instructed to avoid any methylxanthine-containing products for at least 12 hours before the scheduled radionuclide MPI, including caffeinated coffee, tea and beverages, caffeine-containing medications, and aminophylline and theophylline — these substances antagonize adenosine receptors and weaken the stress effect
• Mechanism and pharmacology research: For experiments on selective A2A receptor agonism, coronary blood flow and flow reserve assessment, and A1/A2A/A2B/A3 subtype selectivity comparisons; also studied in animal models for enhancing compound delivery across the blood–brain barrier to the central nervous system
• Investigational directions: Multiple clinical trials are evaluating its use in myocardial ischemia, coronary artery disease, myocardial blood flow reserve, and in combination with coronary CT imaging
• Formulation and manufacturing: For formulation development of injections (5 mL:0.4 mg, 0.08 mg/mL) and prefilled syringes; because the API is practically insoluble in water, the formulation core is solving solubilization (propylene glycol system), the pH stability window (6.3–7.7) and sterility assurance; suitable for analytical method development and validation, related-substance research, stability studies, and GMP scale-up with CMO / CDMO contract manufacturing

Safety notice: This product is an active pharmaceutical ingredient (API) intended solely for compliant industrial, research and pharmaceutical manufacturing use; it is not for end clinical use or guidance for self-administration. The finished product is a prescription drug and is contraindicated in patients with second- or third-degree atrioventricular block or sinus node dysfunction (except in patients with a functioning artificial pacemaker). Common adverse reactions include dyspnea, headache, flushing, chest discomfort, dizziness, angina pectoris, chest pain and nausea. Because it may cause coronary steal and hemodynamic fluctuations, cardiopulmonary resuscitation equipment and personnel must be available during administration. Wear protective gloves, protective clothing, and eye and face protection when handling the API; avoid dust inhalation.

Product information: please contact us. This information is for reference only.