Abstract
The interaction of calmodulin antagonists and hydrophobic calcium antagonists with calmodulin and calcium antagonist ( [3H]nitrendipine and [3H]diltiazem) binding sites was investigated. The classical calmodulin antagonists calmidazolium, trifluorperazine, and W-7 were active at similar concentrations in the three experimental systems. The hydrophobic calcium antagonists prenylamine and bepridil, however, interacted with [3H]diltiazem binding at concentrations up to 50 times lower than their calmodulin inhibiting concentrations. The structural requirements for binding to calmodulin and to calcium channels are thus not identical for these hydrophobic drugs, suggesting that the calcium channel interacting properties of these antagonists are not a direct consequence of their calmodulin binding properties.
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