Interaction of antiestrogens with binding sites for muscarinic cholinergic drugs and calcium channel blockers in cell membranes.

The interaction of tamoxifen and clomifene with membrane binding sites for the cholinergic ligand quinuclidinyl benzilate (QNB) and the dihydropyridine calcium antagonist nitrendipine was studied. Both tamoxifen and clomifene competed with [3H]-QNB and [3H]-nitrendipine for their binding to the receptor in the membrane fractions from the urinary bladder and myometrium. The extent of inhibition as judged by the Ki values for both antiestrogens was similar at both receptor sites. The data suggest that the antiproliferative effects of tamoxifen may involve not only the intracellular estrogen-receptor system but also receptors for neurotransmitters and membrane calcium channels.