Drotaverine interacts with the L-type Ca(2+) channel in pregnant rat uterine membranes

The effect of the isoquinoline derivative, drotaverine on the specific binding of [(3)H]nitrendipine and [(3)H]diltiazem to pregnant rat uterine membranes was examined. Drotaverine inhibited the specific [(3)H]nitrendipine and [(3)H]diltiazem bindings with IC(50) values of 5.6 and 2.6 microM, respectively. Saturation studies showed that diltiazem caused a significant increase in the maximum binding density without changing the K(D) of [(3)H]nitrendipine while drotaverine increased both the K(D) and the B(max) of [3H]nitrendipine. The dissociation kinetics of both [3H]nitrendipine and [(3)H]diltiazem were accelerated by drotaverine. These results suggest that drotaverine has a negative allosteric interaction with the binding sites for 1,4-dihydropyridines and 1,5-benzothiazepines on the L-type CA(2+) channel in pregnant rat uterine membranes, which may have implications as to the potential usefulness of this drug in aiding child delivery.