BRL 8242（2-[2-苯并咪唑基]-氨基-2-咪唑啉二盐酸盐），一种具有抗高血压活性的新型多巴胺-β-羟化酶抑制剂。

BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride), a new inhibitor of dopamine-beta-hydroxylase with antihypertensive activity.

作者信息

Claxton I M, Palfreyman M G, Poyser R H, Whiting R L

出版信息

Eur J Pharmacol. 1976 May;37(1):179-88. doi: 10.1016/0014-2999(76)90020-0.

Abstract

BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride) was found to inhibit dopamine-beta-hydroxylase in vitro and in vivo and to have antihypertensive activity. The effect on dopamine-beta-hydroxylase in vitro was shown by inhibition of the conversion of phenylethylamine to phenylethanolamine, using enzyme extracted from rat adrenals. In vivo, BRL 8242 inhibited 3H-noradrenaline but not 3H-dopamine biosynthesis from 3H-L-dopa in rat brain. Furthermore, the compound lowered endogenous noradrenaline levels in both rat brain and heart whilst increasing the concentration of brain dopamine. In both metacorticoid hypertensive and normotensive rats, BRL 8242 lowered blood pressure. This response was dose related and correlated well with the reduction of endogenous noradrenaline in the tissues examined. It is therefore suggested that the inhibition of dopamine-beta-hydroxylase by BRL 8242 may account for its blood pressure lowering activity.

摘要

BRL 8242（2-[2-苯并咪唑基]-氨基-2-咪唑啉二盐酸盐）在体内外均能抑制多巴胺-β-羟化酶，并具有降压活性。利用从大鼠肾上腺提取的酶，通过抑制苯乙胺向苯乙醇胺的转化，证实了其对多巴胺-β-羟化酶的体外作用。在体内，BRL 8242抑制了大鼠脑中3H-去甲肾上腺素的合成，但不影响3H-L-多巴生成3H-多巴胺。此外，该化合物降低了大鼠脑和心脏中的内源性去甲肾上腺素水平，同时提高了脑内多巴胺的浓度。在促肾上腺皮质激素性高血压大鼠和正常血压大鼠中，BRL 8242均能降低血压。这种反应与剂量相关，并且与所检测组织中内源性去甲肾上腺素的减少密切相关。因此，提示BRL 8242对多巴胺-β-羟化酶的抑制作用可能是其降压活性的原因。