A new type of Ca-channel modulation by a novel class of 1,4-dihydropyridines

被引:7
作者
Bechem, M
Goldmann, S
Gross, R
Hallermann, S
Hebisch, S
Hutter, J
Rounding, HP
Schramm, M
Stoltefuss, J
Straub, A
机构
[1] BAYER AG,INST CARDIOVASC RES,D-42096 WUPPERTAL,GERMANY
[2] BAYER AG,CHEM RES LABS,D-42096 WUPPERTAL,GERMANY
关键词
BAY Y 5959; 1,4-dihydropyridines; Ca-channel; Ca-channel modulating drugs; heart failure; Ca-promoters;
D O I
10.1016/S0024-3205(96)00600-5
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Both Ca-antagonistic as well as Ca-agonistic 1,4-dihydropyridines (DHPs) have become extremely important tools to investigate the role of Ca-channels under various physiological and pathophysiological conditions. While Ca-antagonists stabilize the inactivated state of the Ca-channel without influencing the voltage dependent open and closed times, Ca-agonists prolong the mean open time of the channel. We here report for the first time the effects of a novel DHP, BAY Y 5959, which modulates Ca-channel gating in a unique manner: It increases both the mean open time and the mean closed time of the Ca-channel by binding to the DHP receptor. This results in a reduced rate of Ca-current activation, an increased peak current, and a strongly prolonged tail current decay. All these effects are strongly voltage dependent. Therefore it depends on resting membrane potential and shape of the action potential whether and how the Ca-influx into the cell is influenced. This novel mode of action of BAY Y 5959 results in an interesting pharmacological profile: It has a strong positive inotropic effect in the heart without influencing vessel tone. Therefore the term Ca-promoter is suggested; it could become a new approach for the drug treatment of congestive heart failure.
引用
收藏
页码:107 / 118
页数:12
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