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      Effects of L-Threo-3,4-Dihydroxyphenylserine on Orthostatic Hypotension in Hemodialysis Patients

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          Background: Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine ( L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase. Methods: A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24–52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study. Results: In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions. Conclusions: These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.

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          Studies on the activity of l-THREO-3,4-dihydroxyphenylserine (l-DOPS) as a catecholamine precursor in the brain comparison with that of l-DOPA

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            Clinical Effects of L -Threo-3,4-Dihydroxyphenylserine on Orthostatic Hypotension in Hemodialysis Patients

            Orthostatic hypotension is one of the major factors interfering with everyday activities in hemodialysis patients, but there has been no effective agent for treating it. In order to clarify the clinical effects of L -threo-3,4-dihydroxyphenylserine ( L -DOPS) on orthostatic hypotension of hemodialysis patients, we conducted a randomized, double-blind comparative trial. 149 regular hemodialysis patients with orthostatic hypotension were randomly allocated to three groups and L -DOPS at doses of 400 mg, 200 mg or placebo was orally administrated to each group 30 min before starting every hemodialysis for 4 weeks. Changes of blood pressure (BP) in orthostatic hypotension immediately after completion of hemodialysis and symptoms related to orthostatic hypotension were compared between the three groups. In the 400-mg group, systolic and diastolic BP after standing increased significantly and the drop of mean BP after standing was also reduced compared with pretreatment levels. No such changes were observed in the placebo group. Fatiguability, malaise/weakness, dizziness and light-headed feeling, the interdialytic symptoms commonly observed in hemodialysis patients who developed orthostatic hypotension, were improved to a significant extent in the L -DOPS group compared with the placebo group. In particular, the improvement was more remarkable for the L -DOPS 400-mg group than the placebo group in patients with diabetic nephropathy, lower systolic BP after standing, and the long duration type of orthostatic hypotension. The incidence of adverse events was comparable between the three groups, and all recovered after discontinuation of L -DOPS or concomitantly administered drugs, or without any treatment. These findings indicate that L -DOPS taken before hemodialysis prevents orthostatic hypotension in patients undergoing hemodialysis, and is also effective for the interdialytic symptoms related to orthostatic hypotension.

              Author and article information

              Am J Nephrol
              American Journal of Nephrology
              S. Karger AG
              August 2002
              02 August 2002
              : 22
              : 4
              : 338-346
              aYodogawa Christian Hospital, Osaka, bDepartment of Internal Medicine, Fujigaoka Hospital, Syowa University, Yokohama, cCenter of Blood Purification Therapy, Wakayama Medical College, Wakayama, dDepartment of Nephrology, Osaka Prefectural Hospital, Osaka, eSecond Department of Internal Medicine, Tokyo Medical and Dental University, Tokyo, fKidney Center, Tokyo Women’s Medical University, Tokyo, gDepartment of Internal Medicine II, Tokyo Jikei University School of Medicine, Tokyo, hDepartment of Internal Medicine, Sakai Hospital, Kinki University School of Medicine, Osaka, iMasuko Memorial Hospital, Nagoya, and jShinrakuen Hospital, Niigata, Japan
              65224 Am J Nephrol 2002;22:338–346
              © 2002 S. Karger AG, Basel

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              Figures: 6, Tables: 2, References: 17, Pages: 9
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