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In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
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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 lines
Guinea-pig ventricular myocytes
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.
Reacting condition
10 ~ 100 μM; 8 ~ 10 mins
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 models
A dog model of coronary ischemia-reperfusion
Dosage form
6.6 μg/kg/min; i.v.
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.
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.
References:
[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.