L-type calcium (Ca2+) channel mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm. Calcium channel also plays an important role in excitation-contraction coupling in the heart and is required for normal heart development and normal regulation of heart rhythm.
Nitrendipine is a L-type calcium channel inhibitor. Based on experiments performed on a whole-cell voltage clamp current recording system, nitrendipine blocked Ca2+ currents potently with half-block by subnanomolar concentrations. The concentration dependence of block had the form expected for 1:1 binding, with an apparent dissociation constant (Kd) of 0.36 nM[3]. In a radioligand binding assay, 3H labeled nitrendipine specifically binded to the microsomal fraction from isolated guinea-pig ileal longitudinal muscle, and the binding pattern was saturable and linear with protein concentration and reversible. The apparent equilibrium dissociation constant was 1.63 ± 0.06 ×10-10 M and the maximum site density was 1.13 ± 0.03 pmol/mg of protein, as determined from scatchard analysis of equilibrium binding at 25ºC[4].
Nitrendipine/尼群地平 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bovine aortic endothelial cells (BAEC)
0.1 to 100 µM
3 minutes
Nitrendipine significantly increased intracellular calcium concentration in BAEC in a concentration-dependent manner, from a control level of 118±10 nM by 11±2 nM (0.1 μM), 23±3 nM (1 μM), 34±4 nM (10 μM), and 47±5 nM (100 μM). This elevation is mainly due to a gadolinium-sensitive calcium influx from the extracellular space rather than a calcium release from intracellular stores.
Br J Pharmacol. 1996 Aug;118(8):1899-904
Nitrendipine/尼群地平 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
Hypertensive model
Oral
200 mg/kg
Single dose
To compare the bioavailability of nanocrystals, physical mixture, and commercial tablet. Results showed that the Cmax of the nanocrystals was approximately 15-fold and 10-fold greater than that of physical mixture and commercial tablet, respectively, and the AUC0→24 was approximately 41-fold and 10-fold greater, respectively.
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