A comparison of the effects of cinnarizine and related compounds on [ 3H]nitrendipine binding in the brain, heart and ileum

Abstract

The influence of cinnarizine, flunarizine and lidoflazine on [ 3H]nitrendipine binding in the cerebral cortex, heart and longitudinal muscle of the ileum was investigated. When assays were run in Ca++ free Tris/HCl buffer on extensively washed tissue homogenates, cinnarizine, flunarizine and lidoflazine were approximately equipotent inhibitors of [ 3H]nitrendinpine binding in the heart and cerebral cortex. with Ki values of approximately 10 −6 M. In contrast, the compounds were 4 to 100 times more potent in the ileum with the rank order of potency being: lidoflazine> flunarizine>cinnarizine. The same rank order of potency was observed in the ileum when assays were run in the presence of 1 mM Ca++, although all three drugs were somewhat less potent. Similarly, Ca++ inhibited the binding of the cinnarizine-like drugs in the cerebral cortex and heart as well, with all drugs being less potent than that observed in the ileum under similar assay conditions.