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.

Urinary phenylethylamine excretion: gas chromatographic assay with electron-capture detection of the pentafluorobenzoyl derivative.

Phenylethylamine was extracted into n-hexane from alkaline urine saturated with sodium chloride, and back-extracted into dilute acid. The extract was freeze-dried and the residue converted to a pentafluorobenzoyl derivative for analysis by gas chromatography on a column of OV-225 with electron-capture detection. Quantification was achieved by adding an internal standard of tolylethylamine to each sample prior to extraction. Output values in normal subjects and in some patients with phenylketonuria and hyperphenylalaninaemia were in agreement with those in some other recent reports.