The pharmacokinetics of oral L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, and L-threo-DOPS in plasma and urine was determined by high performance liquid chromatography with an electrochemical detector after separation on a boric acid gel column. L-threo-DOPS was slowly absorbed by normal subjects; the maximum plasma concentration occurred 3 h after administration and 20% of the oral dose was recovered unchanged in the urine within 12 h. It induced a substantial elevation of plasma norepinephrine levels, the peak being attained at 5 h, but without any change in blood pressure. In the patients, the absorption and metabolism of L-threo-DOPS were delayed, and a prolonged pressor response was observed, with a peak after 8 h. It was concluded that the effects on plasma norepinephrine and blood pressure of oral L-threo-DOPS were essentially equal to those of twice as large a dose of DL-threo-DOPS.

We have examined the kinetics of oral L-threo-3,4-dihydroxyphenylserine (DOPS) alone and combined with peripheral decarboxylase inhibitors in patients with Parkinson's disease and other degenerative diseases of the brain. Combined administration of L-threo-DOPS and carbidopa or benserazide produced higher plasma concentrations of L-threo-DOPS and suppressed the increase in plasma norepinephrine. This finding indicates some advantages of combined therapy with L-threo-DOPS and decarboxylase inhibitors. Measurable quantities of DL-threo-DOPS were found in the CSF during repeated administration, but there was no consistent change in norepinephrine concentration.

Orthostatic hypotension in a patient with Shy-Drager syndrome was treated for 6 months with oral DL-threo-3,4-dihydroxyphenylserine (DL-threo-DOPS). Adrenergic function was evaluated before and during treatment by measurements of changes in blood pressure and plasma norepinephrine on head-up tilting and by the response of blood pressure to the Valsalva maneuver and infused norepinephrine. After the patient received DL-threo-DOPS, the fall in his mean arterial blood pressure on head-up tilting was reduced and he had no syncope when standing. When peripheral decarboxylase inhibitor was combined with DL-threo-DOPS, the same beneficial effect on orthostatic hypotension was observed.

SummaryBlood samples from 21 patients with familial amyloid polyneuropathy (FAP) and 81 normal family members among 7 affected families in Arao were tested for 9 blood group systems, 8 serum polymorphic proteins, 12 red cell polymorphic enzymes, and HLA. One of the most important findings was the existence of two relatively rare variants, i.e., group specific component Gc*IA2 and phosphoglucomutase PGMI*7 in 3 families. This observation suggests that the three genealogically independent families may have a common ancester. Phenotype AB in the ABO blood group system, phenotype 1 in the haptoglobin system, and M2 gene in the protease inhibitor system were not seen, and phenotype Jk(a+b-) in the Kidd groups was found in only one patient. Whether these observations reflect the characteristics of FAP in the Arao district or that of FAP itself can not be determined from the present study. No phenotype attributable to Caucasians was found, hence the study provides no support for the hypothesis that the gene for FAP was introduced into Japan by the Portuguese.

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