ICI 206,970: a novel calcium channel blocker with eukalemic diuretic activity.
ICI 206,970 is a novel eukalemic diuretic from the aminomethylphenol pyrazine series which exhibited a calcium antagonist profile. The isolated rat aorta evaluation and dihydropyridine ligand [3H]-PN 200-110 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.
Howe
B B
BB
Department of Pharmacology, ICI Pharmaceuticals Group, Wilmington, DE 19897.
Keith
R A
RA
Do
M L
ML
Halterman
T J
TJ
Donahue
J Y
JY
Schwartz
J A
JA
Kau
S T
ST
D000818:Animals; D001011:Aorta / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006332:Cardiomegaly / Q000188:drug therapy; D003326:Coronary Circulation / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D002121:Calcium Channel Blockers; D004232:Diuretics; D011719:Pyrazines; C079771:ICI 206970