Dissociation of biochemical and hypotensive effects of debrisoquine in hypertensive patients.

The 24 h urinary excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and vanillylmandelic acid, plasma renin activity and plasma and urinary debrisoquine were measured before and during chronic treatment with oral debrisoquine in 14 in-patients with essential hypertension. There was a significant fall (mean ±SD) in the 24 h urinary excretion of vanillylmandelic acid (15.3±2.8 to 6.7±1.9 µmol) noradrenaline (199.0±105.8 to 125.2±43.3 nmol) and plasma renin activity (0.71±0.47 to 0.40±0.20 pmol Angio I ml−1 h−1) while the urinary normetadrenaline/noradrenaline ratio increased (10.4±6.1 to 17.1±5.1). No significant change was seen in the output of adrenaline or of O-methylated metabolites. Debrisoquine produces extensive noncompetitive inhibition of platelet monoamine oxidase in vivo at low therapeutic plasma concentrations. These changes support the view that treatment with debrisoquine produces intraneuronal inhibition of monoamine oxidase and post-ganglionic blockage. There was a significant correlation between the change in standing diastolic blood pressure and the daily dose (rs=−0.52), pre-dose plasma concentration (rs=−0.85) and mean daily urinary recovery (rs=−0.80), of debrisoquine. The full extent of the biochemical changes were seen at low dose and low plasma concentration and were not directly correlated with the fall in standing or supine blood pressure.