A calcium channel inhibitor
Nisoldipine(BAY-k 5552; Sular) is a calcium channel blocker belonging to the dihydropyridines class, specific for L-type Cav1.2 with IC50 of 10 nM. IC50 value: 10 nMTarget: L-type Cav1.2Nisoldipine is a potent blocker of L-type calcium channels. Nisoldipine binds directly to inactive calcium channels stabilizing their inactive conformation Similar to other DHP CCBs. Nisoldipine displays selectivity for arterial smooth muscle cells due to great number of inactive channels and the α1 subunit of the channel. Nisoldipine is about 30 times less selective for delayed-rectifier K+ channels than for L-type Ca2+ channels, which inhibits IKr (rapidly activating delayed-rectifier K+ current) with IC50 of 23 μM, and IKs (slowly activating delayed-rectifier K+ current)with IC50 of 40 μM in guinea-pig ventricular myocytes. Nisoldipine also displays antioxidant potency with IC50 of 28.2 μM both before and after the addition of active oxygen.
参考文献:
[1]. Hamilton SF, Houle LM, Thadani U. Rapid-release and coat-core formulations of nisoldipine in treatment of hypertension, angina, and heart failure. Heart Dis. 1999 Nov-Dec;1(5):279-88.
[2]. Fodor JG. Nisoldipine CC: efficacy and tolerability in hypertension and ischemic heart disease. Cardiovasc Drugs Ther. 1997 Jan;10 Suppl 3:873-9.
[3]. D.J. Duncker, J.M. Hartog, P.G. Hugenholtz, et al. The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital - anaesthetized pigs with or without β-adrenoceptor blockade. British Journal of Pharmacology. 1986,88(1): 9-18
[4]. Jan W. De Jong, Tom Huizer, Jan G.P. Tijssen. Energy conservation by nisoldipine in ischaemic heart. British Journal of Pharmacology. 1984, 83(4): 943-949
| Kinase experiment [1]: | |
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Binding experiments of electrophysiology |
CHO cells expressing the subunit of the voltage-dependent L-type Ca2+ channel were cultrured in medium without serum in the presence of different concentrations of Nisoldipine. Then Ca2+ channel current elicited from a holding potential of -100 mV or -50 mV was recorded at room temperature with the whole-cell configuration of the patch-clamp method using the List EPC-7 patch-clamp amplifer and pClamp software. The IC50 values were calculated. |
| Cell experiment [2]: | |
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Cell lines |
Guinea-pig ventricular myocytes |
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Preparation method |
The solubility of this compound in DMSO is > 11.6 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
10 ~ 100 μM; 8 ~ 10 mins |
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Applications |
In guinea-pig ventricular myocytes, Nisoldipine inhibited rapidly activating delayed-rectifier K+ current (I(Kr) ) with an IC50 value of 23 μM, as well as slowly activating delayed-rectifier K+ current (I(Ks) ) with an IC50 value of 40 μM. It was estimated that Nisoldipine is approximately 30 times more selective for L-type Ca2+ channels than for delayed-rectifier K+ channels. |
| Animal experiment [3]: | |
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Animal models |
A dog model of coronary ischemia-reperfusion |
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Dosage form |
6.6 μg/kg/min; i.v. |
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Applications |
Compared with the control group, the Nisoldipine treatment group showed similar hemodynamic measurements. However, mass of necrosis and mass at risk was obviously lower in the Nisoldipine group. In a dog model of coronary ischemia-reperfusion, Nisoldipine reduced the infarct size. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Morel N, Buryi V, Feron O, Gomez JP, Christen MO, Godfraind T. The action of calcium channel blockers on recombinant L-type calcium channel alpha1-subunits. Br J Pharmacol. 1998 Nov;125(5):1005-12. [2]. Missan S1, Zhabyeyev P, Dyachok O, Jones SE, McDonald TF. Block of cardiac delayed-rectifier and inward-rectifier K+ currents by nisoldipine. Br J Pharmacol. 2003 Nov;140(5):863-70. [3]. Hammerman H, Moscovitz M, Hir J. Beneficial effect of nisoldipine in repeated coronary reperfusion. Coron Artery Dis. 1997 Feb;8(2):97-100. | |
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