SPECIFIC-INHIBITION OF CA-ACTIVATED K-CHANNELS IN RED-CELLS BY SELECTED DIHYDROPYRIDINE DERIVATIVES

1 Thirty two dihydropyridine derivatives were screened as potential in hibitors of the Ca-activated K-channel in human red cells. 2 Three der ivatives (26, 29, 32 see Tables 1 and 2) with high activity were then characterized in detail, and also tested against the smooth muscle Ca- channel and shown to have varying potencies. 3 One of the more potent derivatives (32) and nitrendipine were also tested on the Ca-activated K-channel, Maxi-K channel, from mouse pancreatic beta-cells. 4 We con clude from our results that it may be possible to develop selective Ga rdos-channel inhibitors based on these molecules, which may be of bene fit in the treatment of sickle cell disease.