A comparison of the effects of cinnarizine and related compounds on [3H]nitrendipine binding in the brain, heart and ileum.
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] nitrendipine 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 greater than flunarizine greater than 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.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels; D002936:Cinnarizine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005444:Flunarizine; D007082:Ileum / Q000378:metabolism; D008013:Lidoflazine / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism
D015220:Calcium Channels; D010879:Piperazines; D011978:Receptors, Nicotinic; D002936:Cinnarizine; D008013:Lidoflazine; D005444:Flunarizine; D002118:Calcium