Effects of KB-2796, a new calcium antagonist, and other diphenylpiperazines on [3H]nitrendipine binding.

The effect of KB-2796, a new diphenylpiperazine calcium antagonist, on [3H]nitrendipine ([3H]NTD) binding was investigated in synaptosomal membranes prepared from the guinea pig cerebral cortex. KB-2796 inhibited [3H]NTD binding in a dose-dependent manner with an IC50 value of 86 nM. In this respect, KB-2796 was the most potent among the diphenylpiperazine derivatives tested. Saturation binding data indicated that this inhibition resulted from a decrease in the binding affinity without changes in the maximal number of binding sites. KB-2796, however, significantly increased the dissociation rate constant of [3H]NTD from radiolabeled membranes. This finding suggests that KB-2796 inhibits [3H]NTD binding by a negative heterotropic allosteric mechanism. Other diphenylpiperazines tested also showed similar inhibitory properties. Diphenylpiperazines may act at a site, which is different from the 1,4-dihydropyridine binding site, on the voltage-dependent calcium channel.