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The effects of MK‐486, an inhibitor of peripheral aromatic l‐amino acids decarboxylase, on certain urinary metabolites derived from orally administered l‐2‐14C‐dopa were studied in 3 patients with Parkinson's disease. Each patient received, after an overnight fast, 50 p.c of l‐2‐14C‐dopa (100 mg.). Urine and blood were collected serially and assayed for dopa and its major metabolites. This metabolic profile was compared with that obtained after the same dose of l‐2‐14C‐dopa but following pretreatment with MK‐486 (100 mg. in a single dose and 100 mg. given 3 times a day for 7 consecutive days). Plasma and urine specimens were subjected to ion‐exchange resin and alumina chromatography in order to separate dopa and its major metabolites prior to quantitative determinations. Plasma radioactivity half‐life increased from base line of 3 to 15 hours following pretreatment with MK‐486 in a single dose or after one week of therapy. Further, peak plasma dopa fraction radioactivity was increased threefold. Prior to MK‐486 treatment, 43 per cent and 81 per cent of total radioactivity administered were excreted at 2 and 8 hours, respectively. Following MK‐486 pretreatment (100 mg., single dose), only 13 per cent and 37 per cent of administered radioactivity were excreted at these same intervals. Similarly, a single dose of MK‐486 decreased dopamine from base‐line values of 2.6 and 7 mg. to 0.7 and 2.2 mg. at 2 and 8 hours, respectively. Similar trends for radioactivity and dopamine excretion followed multiple dose pretreatment with MK‐486. Homovanillic acid excretion was also decreased by MK‐486. However, MK‐486 did not markedly alter urinary epinephrine and vanilmandelic acid from base line. Pretreatment with MK‐486 reduced radioactivity found in catecholamine fraction by 70 to 80 per cent over the entire 48 hour period studied. Pretreatment with MK‐486 for a period of one week resulted in less inhibition of O‐methylated acid metabolite fraction than that which followed a single dose of MK‐486.

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