A STRUCTURALLY NOVEL INHIBITOR OF CGMP PHOSPHODIESTERASE WITH VASODILATOR ACTIVITY

被引：4

作者：

BOOTH, RFG ^{[1
]}

LUNT, DO ^{[1
]}

LAD, N ^{[1
]}

BUCKHAM, SP ^{[1
]}

OSWALD, S ^{[1
]}

CLOUGH, DP ^{[1
]}

FLOYD, CD ^{[1
]}

DICKENS, J ^{[1
]}

机构：

[1] SEARLE RES & DEV,HIGH WYCOMBE HP12 4HL,BUCKS,ENGLAND

来源：

BIOCHEMICAL PHARMACOLOGY | 1990年 / 40卷 / 10期

关键词：

D O I：

10.1016/0006-2952(90)90728-4

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

A novel, potent, competitive inhibitor of smooth muscle cGMP phosphodiesterase is described (Compound I, [4-[2-n-butyl-5-chloro-1-(2-chlorobenzyl)imidazolyl]methyl] acetate). The compound is highly selective for inhibiting cGMP phosphodiesterase compared with cAMP phosphodiesterase. Compound I inhibits the contraction of smooth muscle in response to a variety of agonists in the same concentration range to that which inhibits the enzyme. Compound I produced a dose-related reduction in the pressor responses to angiotensin II infusion while not inhibiting the responses to bolus doses of angiotensin II. Two structural analogues of Compound I which did not inhibit cGMP phosphodiesterase failed to inhibit smooth muscle contraction in vitro and did not affect angiotensin II pressor responses in vivo. We propose a mechanism to account for the effects of a cGMP phosphodiesterase inhibitor on smooth muscle contraction in vitro and in vivo. © 1990.

引用

页码：2315 / 2321

页数：7

共 39 条

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