Partition of ca 2+ antagonists in brain plasma membranes

Abstract

The partition coefficients ( K p ) of three prototype Ca 2+ antagonists, nitrendipine, (−)-desmethoxyverapamil and flunarizine were determined in native synaptic plasma membranes (SPM) isolated from sheep brain cortex and in liposomes prepared with the total lipids extracted from the membranes. We found that at 25° and at 5 × 10 −6M drug concentration the K p values of the drugs for native SPM are higher than those obtained for liposomes, and are of the order of 334 ± 53, 257 ± 36 and 23 × 10 3 for nitrendipine, (−)desmethoxyverapamil and flunarizine, respectively, whereas the K p values in liposomes are 190 ± 41,118 ± 10 and 6 × 10 3 for the same drugs. These results suggest that the presence of membrane proteins favors the incorporation of the drugs in the membranes. Furthermore, the K p values of the three Ca 2+ antagonists studied increase with temperature in native membranes, but not in liposomes. It is concluded that the physical partitioning in membranes of drugs which act on Ca 2+ channels may play some role in the mechanism of interaction of these drugs with the Ca 2+ channel proteins.