Ranolazine
[CAS# 95635-55-5]

Identification

• Classification: Biochemical >> Inhibitor >> Transmembrane transporters >> Calcium channel inhibitor
• Name: Ranolazine
• Synonyms: N-(2,6-Dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]piperazin-1-yl]acetamide
• Molecular Formula: C₂₄H₃₃N₃O₄
• Molecular Weight: 427.54
• CAS Registry Number: 95635-55-5 (142387-99-3)
• EC Number: 620-450-7
• SMILES: CC1=C(C(=CC=C1)C)NC(=O)CN2CCN(CC2)CC(COC3=CC=CC=C3OC)O

Properties

• Solubility: 10 mM (DMSO)

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08 Danger
• Risk Statements: H301-H302-H315-H319-H335-H336-H361-H373
• Safety Statements: P203-P260-P261-P264-P264+P265-P270-P271-P280-P301+P316-P301+P317-P302+P352-P304+P340-P305+P351+P338-P318-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H336
Reproductive toxicity	Repr.	2	H361
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	3	H301
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	2	H371

Discovery and Applications

Ranolazine is a synthetic antianginal medication that was first introduced in the early 2000s. It was developed to provide a novel approach to managing angina pectoris, a condition characterized by chest pain resulting from reduced blood flow to the heart muscle. Ranolazine's unique mechanism of action and clinical benefits have made it a valuable addition to the treatment options for patients with chronic stable angina.

The discovery of ranolazine is rooted in the quest for new therapies to improve the quality of life for patients with angina. Traditional treatments for angina, such as nitrates, beta-blockers, and calcium channel blockers, primarily focus on reducing the heart's workload or improving blood flow. Ranolazine, however, was developed with a different approach, targeting the underlying pathophysiology of angina at the cellular level.

Ranolazine works by selectively inhibiting the late phase of sodium current in cardiac myocytes, which helps to stabilize the heart's electrical activity. This inhibition reduces the excessive intracellular calcium levels that can occur during periods of ischemia (reduced blood flow). By mitigating calcium overload, ranolazine helps to decrease the myocardial oxygen demand and improve the heart's efficiency. This mechanism is distinct from those of traditional antianginal drugs and provides an additional therapeutic option for managing angina.

The clinical applications of ranolazine are primarily focused on patients with chronic stable angina. It is used as an adjunctive treatment in combination with other antianginal medications when those therapies alone are insufficient to control symptoms. Ranolazine has been shown to improve exercise tolerance and reduce the frequency of angina attacks, thereby enhancing patients' overall quality of life. It does not significantly affect heart rate or blood pressure, which makes it a suitable option for patients who may not tolerate other antianginal drugs well.

Ranolazine is typically administered orally in the form of extended-release tablets. The drug is well-absorbed from the gastrointestinal tract and is metabolized primarily by the liver. Although it has a relatively long half-life, it is usually taken twice daily to maintain effective blood levels. The dosing regimen is adjusted based on the patient's response and any potential interactions with other medications.

One of the key advantages of ranolazine is its safety profile. It is generally well-tolerated, with side effects typically being mild and including dizziness, nausea, and constipation. Importantly, ranolazine does not carry the risk of tolerance or dependence associated with some traditional antianginal drugs, such as nitrates. However, it is essential for patients to be monitored for potential drug interactions, particularly with other medications that affect the liver enzyme systems involved in ranolazine metabolism.

The introduction of ranolazine has expanded the therapeutic options for managing angina, offering an alternative for patients who may not respond adequately to conventional treatments. Its unique mechanism of action and favorable side effect profile make it a valuable addition to the armamentarium of antianginal therapies. As research continues, ranolazine's role in cardiovascular medicine may further evolve, providing additional insights into its potential benefits and applications in treating various aspects of heart disease.

References

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