Influence of the decarboxylase inhibitor benserazide on the antihypertensive effect and metabolism of alpha-methyldopa in patients with essential hypertension.

In a single-blind study, the dopa-decarboxylase inhibitor benserazide (375 mg/day for 3 days and 750 mg/day for further 3 days) and a placebo were given orally in combination with individually effective doses of alpha-methyldopa (mean 1.5 g/day) to 3 hospitalized patients with essential hypertension. Alpha-methyldopa (α-MD) alone lowered blood pressure from 165/107 to 136/93 mm Hg (P<0.05). Benserazide did not alter the hypotensive effect of α-MD, although the decarboxylation of α-MD was markedly reduced, as shown by the urinary excretion of alpha-methyldopamine (α-MDA). During administration of α-MD alone, the ratio α-MD/α-MDA in urine of the 3 patients was 8:1, 7:1 and 22:1, respectively. When benserazide 375 mg/day was added the ratio rose to 31:1, 31:1 and 35:1; the ratio was 37:1, 18:1 and 46:1 at the higher dose of inhibitor. In a double-blind crossover study the effect on blood pressure of 3 weeks of treatment with α-MD (mean 1.75 mg/day), benserazide (375 mg/day), placebo and their combinations were compared in 5 hypertensive subjects. Again, benserazide did not influence the antihypertensive action of α-MD. To study whether benserazide entered the CNS, a single oral dose ofC-benserazide of 125 mg was given to 2 patients who were to undergo diagnostic lumbar puncture. Two hours after intake of the labelled drug, when radioactivity in blood had reached a maximum, the concentration of radioactivity in spinal fluid was less than 1% of the plasma level. Thus, the antihypertensive action of α-MD was not influenced by oral doses of the decarboxylase inhibitor benserazide. The results suggest that benserazide in doses up to 750 mg/day does not affect central decarboxylation of α-MD and that this antihypertensive agent lowers blood pressure by a central action. [ABSTRACT FROM AUTHOR]