title: 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.
mesh_terms: D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency*; D004305:Dose-Response Relationship, Drug; D015103:Droxidopa / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D004837:Epinephrine / Q000652:urine; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy* / Q000209:etiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism; D012694:Serine / Q000031:analogs & derivatives*; D013268:Stimulation, Chemical; D013379:Substrate Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014439:Tyramine / Q000494:pharmacology
chemical_list: D012694:Serine; D004299:Dopamine beta-Hydroxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D015103:Droxidopa; D004298:Dopamine; D009638:Norepinephrine; D014439:Tyramine; D004837:Epinephrine