Clinical Autonomic Research

, Volume 14, Issue 6, pp 363–368 | Cite as

Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure

  • David S. Goldstein
  • Courtney Holmes
  • Horacio Kaufmann
  • Roy Freeman
RESEARCH ARTICLE

Abstract

Background

Oral L-threo-3,4-dihydroxyphenylserine (L-DOPS), a synthetic catechol amino acid, increases standing blood pressure and improves standing ability in patients with neurogenic orthostatic hypotension, by conversion of L-DOPS to norepinephrine (NE) outside the brain. This study assessed the pharmacokinetics of L-DOPS, NE, and dihydroxyphenylglycol (DHPG), the main neuronal metabolite of NE, in patients with primary chronic autonomic failure from pure autonomic failure (PAF) or multiple system atrophy (MSA).

Methods

In 5 MSA and 4 PAF patients, antecubital venous blood was drawn during supine rest and plasma levels of catechols measured at various times for 48 hours after a single oral dose of 400 mg of L-DOPS.

Results

Plasma L-DOPS peaked at 1.9 µg/ml (9 µmol/L) about 3 hours after drug administration, followed by a monoexponential decline with a half-time of 2–3 hours in both patient groups. Plasma NE and DHPG also peaked at about 3 hours, but at much lower concentrations (4 and 42 nmol/L). Compared to the MSA group, the PAF group had a smaller calculated volume of distribution of L-DOPS and up to 10-fold lower plasma NE levels at all time points. Plasma NE was above baseline in MSA even at 48 hours after L-DOPS.

Conclusions

The relatively long half-time for disappearance of L-DOPS compared to that of NE explains their very different attained plasma concentrations. The similar NE and DHPG responses in PAF and MSA suggests production of NE from LDOPS mainly in non-neuronal cells. Persistent elevation of plasma NE in MSA suggests residual release of NE from sympathetic nerves.

Key words

DOPS norepinephrine dihydroxyphenylglycol autonomic failure sympathetic nervous system 

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Copyright information

© Steinkopff Verlag 2004

Authors and Affiliations

  • David S. Goldstein
    • 1
    • 2
  • Courtney Holmes
    • 1
  • Horacio Kaufmann
    • 3
  • Roy Freeman
    • 4
  1. 1.Clinical Neurocardiology SectionNational Institute of Neurological Disorders and Stroke National Institutes of HealthBethesda (MD)USA
  2. 2.NINDS, NIH, 10 Center Drive MSC-1620 Building 10 Room 6N252Bethesda (MD)USA
  3. 3.Mount Sinai School of MedicineNew York (NY)USA
  4. 4.Beth Israel Deaconess Medical CenterBoston (MA)USA

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