Landiolol hydrochloride
[CAS# 144481-98-1]

Identification

• Classification: API >> Circulatory system medication >> Beta-adrenergic receptor blocker
• Name: Landiolol hydrochloride
• Synonyms: [(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl 3-[4-[(2S)-2-hydroxy-3-[2-(morpholine-4-carbonylamino)ethylamino]propoxy]phenyl]propanoate hydrochloride
• Molecular Formula: C₂₅H₃₉N₃O₈.HCl
• Molecular Weight: 546.05
• CAS Registry Number: 144481-98-1
• EC Number: 833-743-1
• SMILES: CC1(OC[C@H](O1)COC(=O)CCC2=CC=C(C=C2)OC[C@H](CNCCNC(=O)N3CCOCC3)O)C.Cl

Properties

• Solubility: 25 mg/mL (H2O)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319
• Safety Statements: P264-P264+P265-P280-P302+P352-P305+P351+P338-P321-P332+P317-P337+P317-P362+P364

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315

Discovery and Applications

Landiolol hydrochloride is a pharmaceutical compound that has garnered attention for its potential in the treatment of cardiovascular conditions, particularly in the management of acute heart failure and arrhythmias. This substance is a beta-blocker, which works by selectively inhibiting the beta-1 adrenergic receptors in the heart. By blocking these receptors, landiolol hydrochloride reduces heart rate and myocardial oxygen demand, making it useful in controlling arrhythmias and stabilizing heart function in acute situations. Its selectivity for the beta-1 receptor is what sets it apart from other beta-blockers, as it minimizes the risk of side effects such as bronchospasm, which is more commonly seen with non-selective beta-blockers.

The discovery of landiolol hydrochloride can be traced back to the early 1990s when researchers were looking for a more effective and safer option for controlling heart rate in patients with acute cardiovascular conditions. Unlike traditional beta-blockers, which can have long-lasting effects, landiolol was developed with a short half-life, which allows for rapid onset and offset of action. This property makes it particularly useful in acute settings, such as during surgery or in the intensive care unit, where precise control of heart rate is needed without the extended effects of other beta-blockers. The compound was developed by Chugai Pharmaceutical Co., Ltd. and was later introduced into clinical practice in Japan and other countries.

The synthesis of landiolol hydrochloride involves several key steps. The first stage typically includes the preparation of the core structure, which is a beta-blocker derivative with an aromatic group linked to a secondary amine. Various synthetic methods, including the use of selective reagents and protective groups, are employed to introduce the necessary functional groups, such as the hydrochloride salt form, which is essential for the compound’s stability and solubility. The synthesis of landiolol hydrochloride is designed to yield high purity, ensuring that the compound is safe for pharmaceutical use and can be administered effectively to patients.

Landiolol hydrochloride has found significant applications in the field of medicine, particularly in the treatment of acute heart conditions. Its ability to rapidly control heart rate makes it useful in emergency situations, such as in the treatment of supraventricular tachycardia or after cardiac surgery. It is also employed in managing intraoperative tachycardia, where maintaining stable heart function is critical for patient safety. Because of its short half-life, landiolol hydrochloride offers the advantage of being easily titrated to the desired dose, minimizing the risk of overdose and other complications. This characteristic makes it an important tool in critical care medicine, especially when precise control over heart rate is required.

In conclusion, landiolol hydrochloride represents a significant advancement in the management of acute cardiovascular conditions. Its selective action on beta-1 receptors and its rapid onset and offset make it particularly suited for use in critical care settings. Ongoing research continues to explore its potential in other therapeutic areas, ensuring its place as a valuable tool in modern medicine.

References

2024-11-27. Mortality in septic patients treated with short-acting betablockers: a comprehensive meta-analysis of randomized controlled trials.
DOI: 10.1186/s13054-024-05174-w

2024-11-26. Personalizing beta-blockade in septic shock: finding the right rhythm and rate for the right patient.
DOI: 10.1007/s00134-024-07731-x

2024-11-25. Heart rate control in septic shock—echocardiographic evaluation and monitoring should be standard.
DOI: 10.1007/s00134-024-07727-7