Plasma Levodopa Levels Research Articles

ADMINISTRATION OF A PERIPHERAL DECARBOXYLASE INHIBITOR WITH L-DOPA TO DEPRESSED PATIENTS

The behavioural and biological effects L-dopa administration in combination with DL-α-methyl-dopa-hydrazine (MK 485) were evaluated in depressed patients. MK 485 (750-1000 mg. daily) and L-dopa (300-1500 mg. daily) were administered on a non-random double-blind basis to nine depressed hospital inpatients with alternating drug and placebo periods in each patient. Three of the patients treated with the drug combination evidenced clearcut improvement, two of them relapsing when placebo was substituted; six showed no change. Those who improved were predominantly retarded. Cerebrospinal-fluid homovanilic-acid (H.V.A.) levels increased modestly (compared with the profound increase observed in patients on L-dopa alone) with no change in 5-hydroxyindole-acetic acid (5-H.I.A.A.). Plasma-dopa levels in two patients receiving 1 g. of L-dopa were equivalent to levels observed in these same patients receiving 100 mg. of L-dopa plus MK 485. The incidence of gastrointestinal side-effects was significantly lower than in patients receiving L-dopa alone. Preliminary experience suggests that α-methyl-dopa-hydrazine is a safe drug capable of inhibiting the peripheral decarboxylation of administered L-dopa. Consequent reduction in the incidence of peripherally based side-effects may allow more rapid attainment of therapeutic levels, and a potentiation of the effects of L-dopa on the central nervous system.