Endogenous restoration of noradrenaline by precursor therapy in dopamine-beta-hydroxylase deficiency.
DL-dihydroxyphenylserine was given by mouth in a single-blind, placebo-controlled trial to two patients with orthostatic hypotension due to dopamine-beta-hydroxylase deficiency, in the hope of providing noradrenaline by endogenous decarboxylation. Dose-dependent increases in blood pressure were obtained over the range 150-600 mg. After 600 mg mean arterial pressure rose 33 and 19 mm Hg and these rises were tightly correlated with an increase in plasma noradrenaline (r = 0.995, p less than 0.001 and r = 0.88, p less than 0.05). Urinary noradrenaline increased from undetectable levels to 338 and 511 micrograms/24 h. Standing time (a correlate of functional capacity) also increased significantly in both patients. No side-effects were noted.
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002986:Clinical Trials as Topic; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency*; D004305:Dose-Response Relationship, Drug; D015103:Droxidopa / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000188:drug therapy / Q000209:etiology; D009638:Norepinephrine / Q000378:metabolism*; D012694:Serine / Q000031:analogs & derivatives*
D012694:Serine; D004299:Dopamine beta-Hydroxylase; D015103:Droxidopa; D009638:Norepinephrine