ICI-206,970 - A NOVEL CALCIUM-CHANNEL BLOCKER WITH EUKALEMIC DIURETIC ACTIVITY

被引:3
作者
HOWE, BB
KEITH, RA
DO, ML
HALTERMAN, TJ
DONAHUE, JY
SCHWARTZ, JA
KAU, ST
机构
[1] ICI AMER INC,ICI PHARMACEUT GRP,DEPT PHARMACOL,WILMINGTON,DE 19897
[2] ICI AMER INC,ICI PHARMACEUT GRP,DEPT CHEM,WILMINGTON,DE 19897
关键词
ICI-206,970; ANTIHYPERTENSION; HYPERTROPHY; CALCIUM CHANNEL BLOCKER;
D O I
10.1159/000139120
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
ICI 206,970 is a novel eukalemic diuretic from the amino-methylphenol pyrazine series which exhibited a calcium antagonist profile. The isolated rat aorta evaluation and dihydropyridine ligand [H-3]-PN 200-1 10 binding studies demonstrated that ICI 206,970, like verapamil and nifedipine, inhibits vascular smooth muscle tone by inhibiting voltage-sensitive calcium channels. ICI 206,970 produced dose-related hypotensive, negative chronotropic, dromotropic, and coronary vasodilator responses after i.v. injection in anesthetized dogs. ICI 206,970, similar to calcium channel blockers and dissimilar to diuretics, produced an acute antihypertensive effect in spontaneously hypertensive rats (SHR), and significant protection against the development of myocardial hypertrophy in SHR after chronic oral treatment for 28 consecutive days. It is concluded that ICI 206,970 is a calcium channel blocker in addition to its novel eukalemic diuretic property.
引用
收藏
页码:369 / 377
页数:9
相关论文
共 25 条
[1]  
BORHANI NO, 1987, J CLIN HYPERTENS, V3, P104
[2]  
CHERCHI A, 1987, J CLIN HYPERTENS, V3, P216
[3]   THE BINDING OF [H-3]-LABELED NITRENDIPINE TO RECEPTORS FOR CALCIUM-CHANNEL ANTAGONISTS IN THE HEART, CEREBRAL-CORTEX, AND ILEUM OF RATS [J].
EHLERT, FJ ;
ROESKE, WR ;
ITOGA, E ;
YAMAMURA, HI .
LIFE SCIENCES, 1982, 30 (25) :2191-2202
[4]  
FRISHMAN WH, 1989, CIRCULATION, V80, P151
[5]  
FURCHGOTT RF, 1953, J PHARMACOL EXP THER, V108, P129
[6]  
GOLDSTEIN A, 1968, BIOSTATISTICS
[7]   ELECTROLYTE DISARRAY AND CARDIOVASCULAR-DISEASE [J].
HOLLIFIELD, JW .
AMERICAN JOURNAL OF CARDIOLOGY, 1989, 63 (04) :B21-B26
[8]  
JOHNSTON PA, 1993, J PHARMACOL EXP THER, V264, P604
[9]  
KAU ST, 1988, PROG PHARMACOL, V6, P1
[10]   ANTIHYPERTENSIVE EFFECT OF A CALCIUM ANTAGONISTIC DRUG - REGRESSION OF HYPERTENSIVE CARDIAC-HYPERTROPHY BY NIFEDIPINE [J].
KAZDA, S ;
GARTHOFF, B ;
THOMAS, G .
DRUG DEVELOPMENT RESEARCH, 1982, 2 (03) :313-323