Nisoldipine, calcium channel blocking

In cardiac cells, there are two time-dependent outward currents which contribute to repolarization of the cell. Both of these outward currents may be decreased by calcium channel blocking drugs. Since an increase in the intracellular Ca2 + concentration activates one of the outward currents (7to), all the calcium channel blocking drugs should reduce Ito [ 159]. This has been shown with D600, nisoldipine and diltiazem [41-43, 159], The other time-dependent outward current (7X, delayed rectifier) is not calcium-activated [ 160]. Hume has found that D600, diltiazem and nisoldipine inhibit 7X in frog atrial cells [ 160]. However, a similar concentration of nisoldipine does not affect 7X in calf Purkinje fibres [43]. 

Nisoldipine is a calcium-channel-blocking agent that inhibits movement of calcium ions across cell membrane in systemic and coronary vascular smooth muscle and myocardium. It is indicated in the treatment of hypertension, alone or in combination with other antihypertensive agents. 

Kass RS and Arena JP, Influence of pHo on calcium channel block by amlodipine, a charged dihydropyridine compound. Implications for location of the dihydropyridine receptor, /. Gen. Physiol, 93(6), 1109-1127 (1989). NB Although the pRg is repeatedly stated as 8.6, no experimental detail is given, nor any reference. The paper also claims an estimated pK value of <3.5 for nisoldipine (ref Hugenholtz PC and Meyer J (eds.), Nisoldipine, Springer-Verlag, Berlin, 3-348 (1987). 

The calcium channel blockers have been found to affect several different subcellular processes (see Figure 7.2) and these effects may contribute to the pharmacological profile of the drugs. However, these actions are mainly seen at higher concentrations of the drugs than the concentrations required for calcium channel blockade. For example, high concentrations of D600, nitrendipine and verapamil have been shown to block the fast sodium channels present in cardiac tissue [44, 153-156], On the other hand, lower concentrations of verapamil do not decrease the maximum rate of depolarization of phase 0 of the action potential (Fmax) [156, 157], Neither diltiazem nor nisoldipine reduces Kmax [7,42]. Since influx of Na+ into the cell via the fast sodium... 

Members of the dihydropyridine class of calcium channel blocker drugs (e.g., nifedipine, nisoldipine) have intrinsically less effect on the cardiac conduction system than other classes. In particular, verapamil has a high degree of SA nodal and AV nodal blockade, and diltiazem has a somewhat lower effect. Bepridil blocks both sodium and potassium channels, and also causes both SA nodal and AV nodal blockade. 

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