Nitrendipine
[CAS# 39562-70-4]

Identification

• Classification: API >> Circulatory system medication >> Prevention and treatment of angina pectoris
• Name: Nitrendipine
• Synonyms: Ethyl methyl 1,4-dihydro-2,6-dimethyl-4-(meta-nitrophenyl)-3,5-pyridinedicarboxylate; 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid ethyl methyl ester
• Molecular Formula: C₁₈H₂₀N₂O₆
• Molecular Weight: 360.36
• CAS Registry Number: 39562-70-4
• EC Number: 254-513-1
• SMILES: CCOC(=O)C1=C(NC(=C(C1C2=CC(=CC=C2)[N+](=O)[O-])C(=O)OC)C)C

Properties

• Solubility: 72 mM (DMSO), <1 mg/mL (water) (Expl.)
• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.554, Calc.^*
• Boiling Point: 488.9±45.0 °C (760 mmHg), Calc.^*
• Flash Point: 249.5±28.7 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Warning
• Risk Statements: H302+H312-H302-H312-H332-H361
• Safety Statements: P203-P261-P264-P270-P271-P280-P301+P317-P302+P352-P304+P340-P317-P318-P321-P330-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Nitrendipine is a calcium channel blocker used primarily in the treatment of hypertension (high blood pressure) and angina (chest pain). It belongs to the dihydropyridine class of calcium channel blockers, which work by inhibiting the influx of calcium ions through L-type calcium channels into the smooth muscle cells of blood vessels and the heart. This action leads to the relaxation of blood vessels, thus reducing blood pressure and decreasing the workload on the heart.

Nitrendipine was first developed in the 1980s as a more selective and potent calcium channel blocker with fewer side effects compared to older agents. It has since become an important therapeutic option in managing hypertension and angina.

The drug works by binding to the L-type calcium channels on the smooth muscle cells of the arterial walls, preventing calcium from entering the cells. Since calcium is a crucial ion for muscle contraction, its blockage leads to the relaxation of smooth muscle and vasodilation (widening of blood vessels). This vasodilation reduces systemic vascular resistance, which in turn lowers blood pressure. In the case of angina, nitrendipine decreases the oxygen demand of the heart by lowering blood pressure and reducing the workload on the heart muscle, thereby alleviating chest pain.

Nitrendipine is commonly used to treat patients with mild to moderate hypertension, and it is sometimes prescribed for angina pectoris, particularly in patients who cannot tolerate other forms of treatment. It can be used as monotherapy or in combination with other antihypertensive agents, such as ACE inhibitors, diuretics, or beta-blockers, to achieve optimal blood pressure control.

The drug is administered orally, usually in the form of extended-release tablets, which allow for more consistent blood levels and help reduce the frequency of dosing. The dosage is adjusted based on the severity of the condition and the patient's response to treatment. Nitrendipine is generally well tolerated, but like other calcium channel blockers, it can cause side effects such as headache, dizziness, peripheral edema (swelling of the legs and ankles), and flushing. In rare cases, more severe side effects such as arrhythmias or liver dysfunction may occur.

The primary advantage of nitrendipine over other calcium channel blockers is its selective action on the blood vessels with minimal effects on the heart, which reduces the risk of heart rate disturbances. It does not significantly affect the sinoatrial (SA) node or atrioventricular (AV) node conduction, which means that it generally does not cause bradycardia (slowed heart rate), a common side effect seen with other calcium channel blockers.

Nitrendipine is contraindicated in patients with hypersensitivity to the drug, severe hypotension, or in those with heart failure, particularly when used in high doses. It should also be used with caution in patients with liver or kidney impairment, and regular monitoring of liver and kidney function may be required during treatment.

In summary, nitrendipine is a calcium channel blocker that plays a significant role in the treatment of hypertension and angina. Its ability to selectively block calcium channels in vascular smooth muscle provides effective blood pressure control with minimal cardiac side effects. As with any medication, careful monitoring and dose adjustment are necessary to ensure its safety and effectiveness in managing cardiovascular conditions.

References

1984. [3H]nitrendipine binding to adrenal capsular membranes. Life Sciences, 35(8).
DOI: 10.1016/0024-3205(84)90417-x

1990. Blood-pressure-lowering effect of carvedilol vs nitrendipine in geriatric hypertensives. European Journal of Clinical Pharmacology, 38(2).
DOI: 10.1007/bf01409490

1990. The use of carvedilol in elderly hypertensive patients. European Journal of Clinical Pharmacology, 38(2).
DOI: 10.1007/bf01409482