title: Effects of KB-2796, a new calcium antagonist, and other diphenylpiperazines on [3H]nitrendipine binding.
abstract: 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.
authors.affiliation: Pharmaceuticals Research Center, Kanebo, Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Iwamoto
authors.forename: T
authors.initials: T
authors.lastname: Morita
authors.forename: T
authors.initials: T
authors.lastname: Kanazawa
authors.forename: H
authors.initials: H
authors.lastname: Ohtaka
authors.forename: K
authors.initials: K
authors.lastname: Ito
mesh_terms: D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005444:Flunarizine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009568:Nitrendipine / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010879:Piperazines; D009568:Nitrendipine; C052424:lomerizine; D005444:Flunarizine