Effect of unnatural noradrenaline precursor on sympathetic control and orthostatic hypotension in dopamine-beta-hydroxylase deficiency

Lancet. 1987 Nov 21;2(8569):1172-5. doi: 10.1016/s0140-6736(87)91318-3.

Abstract

A patient with severe orthostatic hypotension due to dopamine-beta-hydroxylase deficiency was treated with the unnatural aminoacid D,L-threo-3,4-dihydroxyphenylserine (DOPS) in the hope that it would serve as a substrate of aromatic-L-aminoacid decarboxylase to produce (-)-noradrenaline. With a dose of 500 mg twice daily by mouth, blood pressure rose gradually from 100/55 to 145/85 mm Hg, and orthostatic hypotension disappeared. After 4 months' treatment the patient is free of symptoms and able to live a normal life. DOPS switched on the production of noradrenaline and reduced the excessive production of dopamine. During treatment plasma noradrenaline rose normally after standing and after infusion of tyramine, a biogenic amine that liberates stored neurotransmitter from sympathetic nerve terminals. These data demonstrate that in congenital dopamine-beta-hydroxylase deficiency dopamine instead of noradrenaline is released as the sympathetic neurotransmitter but that the integrity of the sympathetic neuron is otherwise intact.

MeSH terms

  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Dopamine / metabolism
  • Dopamine beta-Hydroxylase / deficiency*
  • Dose-Response Relationship, Drug
  • Droxidopa / administration & dosage
  • Droxidopa / blood
  • Droxidopa / therapeutic use*
  • Epinephrine / urine
  • Female
  • Humans
  • Hypotension, Orthostatic / drug therapy*
  • Hypotension, Orthostatic / etiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Norepinephrine / blood
  • Norepinephrine / metabolism
  • Serine / analogs & derivatives*
  • Stimulation, Chemical
  • Substrate Specificity
  • Sympathetic Nervous System / drug effects*
  • Tyramine / pharmacology

Substances

  • Serine
  • Dopamine beta-Hydroxylase
  • Aromatic-L-Amino-Acid Decarboxylases
  • Droxidopa
  • Dopamine
  • Norepinephrine
  • Tyramine
  • Epinephrine