BINDING CHARACTERISTICS OF A NEW 1,5-BENZOTHIAZEPINE, CLENTIAZEM, TO RAT CEREBRAL-CORTEX AND SKELETAL-MUSCLE MEMBRANES

The binding properties of a new 1,5-benzothiazepine, clentiazem (TA-3090), were investigated in rat cerebral cortex and skeletal muscle membranes with [H-3]diltiazem and [H-3]nitrendipine as radioligands. Clentiazem inhibited [H-3]diltiazem binding to cerebral cortex membranes at the same concentrations as diltiazem at 2-degrees-C. However, at 37-degrees-C clentiazem was 3 times more potent to inhibit binding than diltiazem. [H-3]Nitrendipine binding was modulated by clentiazem in a temperature-dependent manner. At 37-degrees-C clentiazem significantly enhanced [H-3]nitrendipine binding to rat cerebral cortex membranes, whereas it has an inhibitory effect on [H-3]nitrendipine binding at 0-degrees-C and no effect at 25-degrees-C. Of two optical isomers of clentiazem and four of diltiazem, only d-cis isomers (clentiazem and diltiazem) increased [H-3]nitrendipine binding, indicating that both compounds have the same stereoselectivity for increasing [H-3]nitrendipine binding. These results suggest that clentiazem binds to the same 1,5-benzothiazepine binding sites as diltiazem but with greater affinity.