 | |
| Names | |
|---|---|
| IUPAC name (RS)-2-(3,4-Dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylamino]-2-isopropylpentanenitrile | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChemSpider |
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| ECHA InfoCard | 100.060.476 |
| EC Number |
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| UNII | |
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| Properties | |
| C26H36N2O4 | |
| Molar mass | 440.584 g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Norverapamil is acalcium channel blocker. It is the main active metabolite ofverapamil.[1] It contributes significantly to the therapeutic effects of verapamil, which include the treatment ofhypertension,angina, andarrhythmias.[2] Despite being a metabolite of verapamil, norverapamil retains much of the pharmacological activity of verapamil, particularly impacting the calcium ion flow throughL-type calcium channels, leading to its therapeutic cardiovascular and vasodilation effects.[3]
Norverapamil inhibits L-type calcium channels located in the heart and blood vessels, leading to several pharmacological effects includingvasodilation,negative inotropy, and negative dromotropy. Norverapamil relaxes the smooth muscles of blood vessels, reducing systemic vascular resistance and consequently lowering blood pressure.[3] Also, by decreasing calcium influx into heart muscle cells, it is able to lower myocardial contractility. This makes it useful in reducing the workload of the heart, particularly in cardiovascular conditions such as angina.[3] Norverapamil is also able to slowatrioventricular (AV) conduction, which is useful in controllingsupra-ventricular arrhythmias by controlling the heart rate through reduced electrical conduction.[2]
Norverapamil is a metabolite of verapamil and is primarily produced by theN-demethylation performed by theCYP3A4 enzyme in the liver.[4] Itshalf-life is approximately 6–9 hours, and it is eliminated primarily throughrenal excretion.[2] As approximately 80% of the drug is protein-bound, its distribution is significantly influenced by factors such as liver function and serum protein levels.[2]
The effects of norverapamil are dose-dependent, with higher doses producing more pronounced effects. In individuals with hepatic or renal impairments, dose adjustments are necessary to avoid potential toxicity due to its slow metabolism.[4]
Norverapamil, like verapamil, interacts withP-glycoprotein (P-gp), as acalcium channel antagonist. P-gp is a membrane transporter that affects the absorption, distribution, and elimination of many drugs.[2] As a substrate, norverapamil’s absorption is influenced by P-gp, while as an inhibitor, it may affect thebioavailability of other drugs that rely on P-gp for elimination.[3] These interactions are clinically significant when used alongside other P-gp substrates, such asdigoxin, increasing their blood concentrations and potentially leading to adverse effects.[5]
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