Possible requirement of phosphonate moiety for efonidipine effects on the sino-atrial node action potential

The effects of efonidipine, a 1,4-dihydropyridine phosphonate, and structur ally related compounds on rabbit sino-atrial node action potential were exa mined with microelectrodes. 3NIC5NZ has a phosphonate moiety identical to t hat of efonidipine at the C5 position of the dihydropyridine ring and a sid e chain identical to nicardipine at C3, while 3NZ5NIC has C5 and C3 side ch ains identical to nicardipine and efonidipine, respectively. All four compo unds decreased the slope and prolonged the early and late phases of pacemak er depolarization. The I;electivity for the late phase against the early ph ase was in the order of efonidipine > 3NIC5NZ >> nicardipine > 3NZ5NIC. Thu s, the phosphonate moiety at C5 position of the may be important for the ch aracteristic prolongation of the late phase pacemaker depolarization by efo nidipine. (C) 2000 Elsevier Science Inc.