Trial reportJournal of clinical pharmacology2011
Effects of carbidopa and entacapone on the metabolic fate of the norepinephrine prodrug L-DOPS.
Trial report in Journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 28 citations in OpenAlex.
- Comparison of the Pharmacokinetics of Droxidopa After Dosing in the Fed Versus Fasted State and with 3-Times-Daily Dosing in Healthy Elderly Subjects.Drugs in R&D · 2018Trial
- Impact of the Norepinephrine Prodrug Droxidopa on the QTc Interval in Healthy Individuals.Clinical pharmacology in drug development · 2018Trial
- Catecholamine metabolism revisited: from neurochemistry to integrative physiology and pathophysiology.Physiological reviews · 2026Review
- Levodopa-Carbidopa Intestinal Gel Improves Symptoms of Orthostatic Hypotension in Patients with Parkinson's Disease-Prospective Pilot Interventional Study.Journal of personalized medicine · 2022Article
- Atomoxetine Does Not Improve Complex Attention in Idiopathic Parkinson's Disease Patients with Cognitive Deficits: A Meta-Analysis.Parkinson's disease · 2020Article
- Neurogenic Orthostatic Hypotension: State of the Art and Therapeutic Strategies.Clinical Medicine Insights. Cardiology · 2020Review
- Pathophysiology and Treatment of Orthostatic Hypotension in Parkinsonian Disorders.Current treatment options in neurology · 2016Review
- Review
- Neurocardiology: therapeutic implications for cardiovascular disease.Cardiovascular therapeutics · 2012Review
- Catecholamines 101.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundL-threo-3,4-dihydroxyphenylserine (L-DOPS), a norepinephrine (NE) prodrug, is investigational for orthostatic hypotension, which occurs commonly in Parkinson's disease. Adjunctive anti-parkinsonian drugs might interact with L-DOPS. We tested whether L-aromatic amino-acid decarboxylase inhibition by carbidopa (CAR) attenuates L-DOPS conversion to NE and blocks the pressor effect of L-DOPS, whereas catechol-O-methyltransferase inhibition by entacapone (ENT) interferes with L-DOPS metabolism and augments the pressor effect.
methodsTwelve patients with autonomic failure took 400 mg of L-DOPS with 200 mg of placebo (PLA), CAR, or ENT on different days. Plasma L-DOPS, NE, and deaminated NE metabolites (dihydroxyphenylglycol [DHPG], dihydroxymandelic acid [DHMA]) were measured.
resultsL-DOPS+PLA and L-DOPS+ENT increased systolic pressure similarly (by 27 ± 8 and 24 ± 9 mm Hg at 3 hours). L-DOPS+CAR did not increase pressure. The peak increase in plasma NE (0.57 ± 0.11 nmol/L) averaged less than 1/15,000 th that in L-DOPS and less than 1/35th that in DHPG+DHMA. CAR prevented and ENT augmented responses of plasma DHPG and DHMA to L-DOPS.
conclusionsAfter L-DOPS administration plasma, NE levels do not increase sufficiently to increase blood pressure. Pressor responses to L-DOPS seem to reflect NE produced extraneuronally that escapes extensive enzymatic deamination and O-methylation and evokes vasoconstriction before reaching the systemic circulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.