Effect of infused L-threo-3,4-dihydroxyphenylserine on adrenergic activity in patients with familial amyloid polyneuropathy.
L-threo-3,4-dihydroxyphenylserine (DOPS), an immediate precursor amino acid of (-)-norepinephrine, was used as a pharmacological tool to investigate the pathophysiology of the peripheral sympathetic nervous system in Type 1 familial amyloid polyneuropathy. Patients with the well-established disorder showed an enhanced pressor response to L-threo-DOPS under conditions that produced no change in normal subjects. While octopamine induced a brisk pressor response, L-threo-DOPS produced a slow and prolonged change in blood pressure, with a marked concomitant increase in urinary excretion of norepinephrine. A slight increase in urinary excretion of total metanephrine was observed in both groups, but there was no significant increase in serum dopamine-beta-hydroxylase activity. Since infusion of dilute norepinephrine into patients also produced a markedly hypersensitive response, the characteristic pressor response to L-threo-DOPS was indicative of denervation supersensitivity of adrenergic receptors to norepinephrine formed enzymatically from L-threo-DOPS.
D000328:Adult; D000686:Amyloidosis / Q000503:physiopathology*; D001341:Autonomic Nervous System; D001794:Blood Pressure / Q000187:drug effects; D004299:Dopamine beta-Hydroxylase / Q000097:blood; D015103:Droxidopa / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology / Q000652:urine; D009655:Octopamine / Q000494:pharmacology; D011674:Pulse / Q000187:drug effects; D012694:Serine / Q000031:analogs & derivatives*; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects*
D009655:Octopamine; D012694:Serine; D004299:Dopamine beta-Hydroxylase; D015103:Droxidopa; D009638:Norepinephrine