ArticleClinical autonomic research : official journal of the Clinical Autonomic Research Society2021
Pharmacokinetics and pharmacodynamics of ampreloxetine, a novel, selective norepinephrine reuptake inhibitor, in symptomatic neurogenic orthostatic hypotension.
Article in Clinical autonomic research : official journal of the Clinical Autonomic Research Society, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02705755 (A Phase 2 Study to Assess the Effect of TD-9855 in Subjects With Neurogenic Orthostatic Hypotension), which is not on this map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase 2 Study to Assess the Effect of TD-9855 in Subjects With Neurogenic Orthostatic Hypotension
Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Mechanism-Based Therapy With Ampreloxetine for Neurogenic Orthostatic Hypotension in Multiple System Atrophy: A Randomized Withdrawal Trial.Neurology · 2026Trial
- Establishing minimally clinically important differences for the orthostatic hypotension questionnaire (OHQ).Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Trial
- Atomoxetine on neurogenic orthostatic hypotension: a randomized, double-blind, placebo-controlled crossover trial.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2024Trial
- Safety and efficacy of ampreloxetine in symptomatic neurogenic orthostatic hypotension: a phase 2 trial.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021Trial
- Approaches for treating cardiovascular symptoms in Parkinson's disease.Therapeutic advances in neurological disorders · 2025Review
- Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review.Cureus · 2023Review
- Autonomic dysfunction in SARS-COV-2 infection acute and long-term implications COVID-19 editor's page series.Journal of thrombosis and thrombolysis · 2021Review
- Norepinephrine reuptake blockade to treat neurogenic orthostatic hypotension.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2021Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAmpreloxetine is a novel, selective, long-acting norepinephrine reuptake (NET) inhibitor being investigated as a once-daily oral treatment for symptomatic neurogenic orthostatic hypotension (nOH) in patients with autonomic synucleinopathies. The purpose of this study was to characterize the pharmacokinetic and pharmacodynamic profiles of ampreloxetine in this target population.
methodsPatients with nOH were enrolled in a multicenter, phase II clinical trial of ampreloxetine (NCT02705755). They received escalating doses over 5 days in the clinical research unit, followed by 20 weeks of open-label treatment and then a 4-week withdrawal. As neurochemical biomarkers of NET inhibition, we assayed plasma concentrations of norepinephrine (NE) and its main intraneuronal metabolite 3,4-dihydroxyphenylglycol (DHPG) pre- and post-ampreloxetine.
resultsThirty-four patients with nOH were enrolled. Plasma ampreloxetine concentrations increased with repeated escalating doses, with peak concentrations observed 6-9 h post-drug administration. The median ampreloxetine dose in the 20-week treatment phase was 10 mg once daily. Plasma ampreloxetine concentrations reached steady state by 2 weeks, with stable plasma levels over 24 h. No influence of age or renal function on ampreloxetine plasma concentrations was observed. On treatment, compared to baseline, plasma NE significantly increased by 71% (p < 0.005), plasma DHPG significantly declined by 22% (p < 0.05), and the NE:DHPG ratio significantly increased (p < 0.001).
conclusionsPersistent elevation of plasma NE levels accompanied by reduced DHPG levels after ampreloxetine suggests reduced neuronal reuptake and metabolism of NE in postganglionic efferent sympathetic neurons. The findings are consistent with long-lasting NET inhibition, which may increase vasoconstrictor tone, supporting once-daily ampreloxetine dosing in patients with nOH.
Indexed as
Identifiers
What OpenQuestion holds
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.