Nisoldipine, a dihydropyridine calcium antagonist, has greater vascular selectivity than other calcium channel antagonists and does not depress the intact myocardium in vivo. It should be taken on an empty stomach. In patients with stable angina pectoris nisoldipine coat-core increases exercise duration, reduces anginal frequency and myocardial ischemia, and is effective as monotherapy or in combination with a beta-blockers[3]. The drug exhibits higher potency, longer duration of action, and a higher binding affinity in vitro and in vivo than nifedipine. The influence of nisoldipine on cardiac stimulus formation and conduction is also very slight in anesthetized animals, and is completely eliminated in awake animals and humans by counter-regulation up to very high doses. Clinically, nisoldipine was found more potent and prolonged in its action in comparison with nifedipine. In comparative studies, nisoldipine, 10 mg once a day, was found equieffective with nifedipine 10 mg three times or 20 mg twice a day in angina or hypertension, respectively[4]. Nisoldipine coat core (CC) is an extended-release formulation that allows nisoldipine to be released gradually over 24 hours, minimizing fluctuations in plasma concentration and providing a good trough/peak ratio. Nisoldipine CC improves cardiac function and exercise tolerance in patients recovering from acute myocardial infarction, without increasing the risk of mortality compared with placebo. It also improves exercise performance in patients with stable angina pectoris[5].
Nisoldipine/尼索地平 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Sea urchin sperm
11 μM
inhibition of the acrosome reaction
Proc Natl Acad Sci U S A. 1985 Mar;82(5):1460-4.
Embryonic stem cell-derived cardiomyocytes (stage 1 and stage 2)
2 μM
To investigate the effect of Nisoldipine on intracellular Ca2+ oscillations, results showed that Nisoldipine did not impair Ca2+ oscillations but lowered steady-state Ca2+ levels.
Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):8259-64.
Rabbit mesenteric artery smooth muscle cells
50 nM
15 minutes
To investigate the inhibitory effect of nisoldipine on single calcium channel activity, results showed that 50 nM nisoldipine almost completely inhibited the activity of both types of calcium channels.
Proc Natl Acad Sci U S A. 1986 Aug;83(15):5746-50.
Rabbit coronary artery smooth muscle cells
4x10^-8 M, 1x10^-13 M
Nisoldipine inhibited the phasic and tonic contraction responses induced by 128 mM K+ in rabbit coronary artery smooth muscle cells, with IC50 values of 4x10-8 M and 1x10-13 M, respectively.
Br J Pharmacol. 1984 Sep;83(1):243-58.
GH3 rat pituitary cells
2 μM
5 minutes
Attenuated inward Ca2+ currents by approximately 80% without interfering with other conductances
Proc Natl Acad Sci U S A. 1985 Feb;82(4):1108-12.
Rat heart
1 nM to 300 nM
15 or 30 minutes
Nisoldipine dose-dependently reduced the efflux of ATP catabolites, with the highest concentration (300 nM) completely suppressing ischemic purine production.
Br J Pharmacol. 1984 Dec;83(4):943-9.
Nisoldipine/尼索地平 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Pigs
Pentobarbital-anaesthetized pigs
Intravenous infusion
0.25, 0.5, 1.0 μg/kg/min
Continuous 10-minute infusions
To study the effects of nisoldipine on cardiovascular performance and regional blood flow, showing dose-dependent decreases in arterial blood pressure (30%), systemic vascular resistance (30%), and left ventricular filling pressure (15%), but increased heart rate (25%) and LVdP/dt max (20%).
Br J Pharmacol. 1986 May;88(1):9-18
Pigs
Conscious pig model of myocardial stunning
Intravenous infusion
0.5 µg/kg/min
Starting 15 min before the first coronary occlusion and ending 30 min after the 10th reperfusion
Nisoldipine significantly attenuated myocardial stunning on day 1 but had no effect on late preconditioning on days 2 and 3.
J Clin Invest. 1996 Jan 15;97(2):562-76
Pigs
Conscious pigs with a fixed chronic coronary artery stenosis
Oral
0.24±0.02 mg/kg and 0.47±0.04 mg/kg
Two doses, 24 hours apart
To study the effects of nisoldipine on regional myocardial blood flow distribution and function in conscious pigs with a fixed coronary artery stenosis. Results showed that nisoldipine did not significantly improve blood flow or function in the post-stenotic myocardium in either group, particularly in animals with severe stenosis.
Br J Pharmacol. 1988 May;94(1):219-27
Ferrets
Isovolumic coronary-perfused heart model
Coronary perfusion
10^-8 M
3 minutes of ischemia followed by 10 minutes of reperfusion
To determine the effects of nisoldipine on intracellular calcium concentration and left ventricular function during ischemia and reperfusion. Nisoldipine significantly reduced the ischemia-induced rise in diastolic and systolic intracellular calcium concentration, and lessened the decrease in contractile function. Nisoldipine significantly accelerated the decline in intracellular calcium concentration during reperfusion and improved recovery of contractility and relaxation. These effects were associated with a significant diminution in ischemic lactate production.
J Clin Invest. 1992 Jun;89(6):2060-5
Rat
Langendorff perfused heart model
Perfusion
1 nM to 300 nM
Single administration, lasting 15 or 30 minutes
Nisoldipine effectively inhibited ATP breakdown during myocardial ischemia, with low doses significantly reducing purine efflux.
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