Development of diltiazem, a calcium antagonist: coronary vasodilating and antihypertensive actions.

We found that the coronary vasodilating action resides in novel 1,5-benzothiazepine derivatives. The calcium antagonistic property of diltiazem has been demonstrated in vascular and visceral smooth muscles as well as in cardiac ventricular muscle. Although the vasodilating action of diltiazem was the most potent in coronary and vertebral artery, it also dilates other peripheral arteries including renal artery. Antihypertensive action of diltiazem has been shown in several experimental models, such as SHR, renal hypertensive and DOCA/saline rats. Diuretic effect of diltiazem was observed in SHR. Following chronic administration of diltiazem to SHR, the increment of blood pressure was significantly lowered without changing body fluid. In addition, hypotensive action of diltiazem by i.c.v. was observed only at a very high dose. We assume that the vasodilating action of diltiazem is primarily involved in the mechanism responsible for its antihypertensive action.