Landiolol Hydrochloride

Product Overview

Landiolol hydrochloride is an ultra-short-acting, highly selective β₁-adrenergic receptor blocker developed by Ono Pharmaceutical of Japan, development code ONO-1101, marketed successively as Onoact (Japan, first launched in 2002) and Rapibloc (EU). Chemically it is a morpholine-class compound — the monohydrochloride salt of (S)-2,2-dimethyl-1,3-dioxolan-4-ylmethyl 3-[4-[(2S)-2-hydroxy-3-[[2-(morpholine-4-carboxamido)ethyl]amino]propoxy]phenyl]propionate — with two defined stereocenters in the molecule.

Pharmacological characteristics: The β₁/β₂ receptor selectivity ratio is approximately 255:1, significantly higher than esmolol (approximately 8-fold); elimination half-life in healthy subjects is approximately 4 minutes, onset of action approximately 30 seconds, and the effect subsides rapidly after discontinuation, facilitating titration. Compared with esmolol, its incidence of hypotension is significantly lower (literature data 11.7% vs 63%), making it friendlier to patients with cardiac insufficiency — it can rapidly reduce heart rate without significantly suppressing myocardial contractility or lowering mean arterial pressure.

Clinical positioning: The EU has approved intravenous landiolol for short-term rapid control of tachyarrhythmias in perioperative and intensive care settings; Japan initially approved it for intraoperative tachyarrhythmias, extended it in 2013 to tachycardic atrial fibrillation/atrial flutter in patients with left ventricular dysfunction, and further extended it in 2019 to life-threatening arrhythmias requiring emergency management. It was approved in China in 2020 and included in Category B of the national medical insurance catalog.

Technical Specifications

• Standards: CHP/USP/EP
• Specification: 0.99 (purity ≥99.0%, HPLC)
• CAS No.: 144481-98-1 (EINECS 1308068-62-2; free base 133242-30-5; KEGG DRUG D01847; ChEBI 31760)
• Molecular formula: C₂₅H₃₉N₃O₈·HCl (notation used by CAS, ChEBI, Cayman and FDA review reports; some databases write it as the adduct formula C₂₅H₄₀ClN₃O₈)
• Molecular weight: 546.05–546.06 g/mol (CAS 546.05, ChEBI 546.061, FDA review report 546.06); monoisotopic mass 545.2504; free base portion 509.6
• Appearance: White to off-white (or beige) crystalline powder/crystals (dosage form labeled as Crystal powder)
• Purity (HPLC): ≥ 99.0% (reagent grade commonly 98.0%–99.5%, may be concurrently controlled by non-aqueous titration)
• Melting point: Approximately 122–128 °C (supplier COA ranges: 122–126 °C, 124.0–128.0 °C; ChemicalBook reports 125.4 °C) — values vary slightly among sources due to differences in measurement methods and purity; for reference
• Specific optical rotation: −11° to −14° (C=4, ethanol, calculated on the dried basis)
• Chemical name: 4-[(2S)-2-Hydroxy-3-[[2-[(4-morpholinylcarbonyl)amino]ethyl]amino]propoxy]-benzenepropanoic acid [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl ester monohydrochloride
• Stereochemistry: Two defined stereocenters, (2S) and (4S)
• Solubility: Freely soluble in water (H₂O 25 mg/mL, clear) and methanol; soluble in DMF; slightly soluble in DMSO and ethanol (sonication required). Sigma-Aldrich records DMSO 1–10 mg/mL, ethanol 0.1–1 mg/mL, PBS (pH 7.2) 1–10 mg/mL
• Computed physicochemical parameters: Density approximately 1.201 g/cm³; boiling point approximately 727.5 °C (760 mmHg, calculated); LogP approximately 2.38; hydrogen bond donors 4 / acceptors 9; rotatable bonds 14
• Storage conditions: Sealed, protected from light, refrigerated at 2–8 °C; hygroscopic — inert gas protection and moisture-proof storage recommended

Applications

• Emergency treatment of perioperative tachyarrhythmias: For the emergency management of tachyarrhythmias such as atrial fibrillation, atrial flutter and sinus tachycardia under hemodynamic monitoring; randomized double-blind placebo-controlled studies have shown it to be significantly superior to placebo
• Prevention of postoperative atrial fibrillation (POAF): Prophylactic administration in the perioperative period of cardiac and other surgery significantly reduces the incidence of POAF within one week after surgery (compared with diltiazem, placebo or no medication)
• Atrial fibrillation/atrial flutter with left ventricular dysfunction: More effective than digoxin; superior to diltiazem in converting postoperative atrial fibrillation to sinus rhythm
• ICU and critical care settings: For heart rate control in critically ill patients such as those with sepsis — reduces heart rate and promotes restoration of sinus rhythm without causing hypotension or hemodynamic deterioration; also used as first-line management of tachyarrhythmias in heart failure patients, and for hemodynamic and stress-response modulation during procedures such as percutaneous coronary intervention (PCI), tracheal intubation/extubation and electroconvulsive therapy
• Clinical advantages: Rapid onset (approximately 30 seconds), short half-life (approximately 4 minutes), high β₁ selectivity (β₁/β₂ approximately 255:1), relatively low risk of hypotension and bradycardia — facilitating titrated use in hemodynamically unstable patients
• Formulation and manufacturing: Compatible with two dosage forms — injectable concentrate (e.g., 20 mg/2 mL) and powder for injection (e.g., 300 mg, 600 mg lyophilized powder); as an API, used for analytical method development and validation, related-substance research, stability evaluation, and GMP scale-up and CMO/CDMO contract manufacturing

Safety notice: This product is an active pharmaceutical ingredient (API) intended solely for legitimate industrial, research and pharmaceutical manufacturing use, and does not constitute end-user clinical or self-administration guidance. The finished product is administered intravenously and must be used by professional medical staff under ECG and blood pressure monitoring; GHS classification: skin irritation (H315) and eye irritation (H319) — wear protective gloves, goggles and a mask when handling.

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