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

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.