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

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.

• Authors: A J Man in 't Veld, F Boomsma, A H van den Meiracker, M A Schalekamp
• Journal: Lancet (London, England) (Lancet) Vol. 2 Issue 8569 Pg. 1172-5 (Nov 21 1987) ISSN: 0140-6736 [Print] England
• PMID: 2890807 (Publication Type: Journal Article)

Chemical References

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

Topics

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