Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients

Am J Nephrol. 2002 Jul-Aug;22(4):338-46. doi: 10.1159/000065224.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autonomic Nervous System Diseases / drug therapy
  • Autonomic Nervous System Diseases / physiopathology
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / adverse effects
  • Cardiovascular Agents / blood
  • Cardiovascular Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Droxidopa / administration & dosage
  • Droxidopa / adverse effects
  • Droxidopa / blood
  • Droxidopa / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypotension, Orthostatic / blood
  • Hypotension, Orthostatic / drug therapy*
  • Hypotension, Orthostatic / etiology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Renal Dialysis / adverse effects*
  • Statistics as Topic / methods

Substances

  • Cardiovascular Agents
  • Droxidopa
  • Norepinephrine