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 structurally related compounds on rabbit sino-atrial node action potential were examined with microelectrodes. 3NIC5NZ has a phosphonate moiety identical to that of efonidipine at the C5 position of the dihydropyridine ring and a side chain identical to nicardipine at C3, while 3NZ5NIC has C5 and C3 side chains identical to nicardipine and efonidipine, respectively. All four compounds decreased the slope and prolonged the early and late phases of pacemaker depolarization. The selectivity for the late phase against the early phase was in the order of efonidipine > 3NIC5NZ >> nicardipine > 3NZ5NIC. Thus, the phosphonate moiety at C5 position of the may be important for the characteristic prolongation of the late phase pacemaker depolarization by efonidipine.
Masumiya
H
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi-City, Chiba, Japan.
Matsuda
T
T
Tanaka
Y
Y
Tanaka
H
H
Shigenobu
K
K
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D009529:Nicardipine