In most patients with neurogenic orthostatic hypotension (nOH), adequate symptomatic relief is not achieved with available pressor agents. Ampreloxetine is a novel, long-acting, norepinephrine reuptake inhibitor being tested as a treatment for nOH in phase III trials. 

Across studies, after 4-weeks on ampreloxetine, venous norepinephrine levels were significantly increased compared to placebo (geometric mean ratio [GMR]±SE): 1.47+0.11), whereas venous DHPG, the main intraneuronal metabolite, were decreased (GMR±SE: 0.78±0.04). Of the 128 subjects that maintained symptomatic improvement at the end of the open-label period, 64 were assigned to continue ampreloxetine and 64 were withdrawn to placebo. Age/sex and diagnostic subtype were equally distributed between the assigned treatment groups. After 6-weeks of randomization,  standing BP at 3-minutes of standing was significantly lower than at the end of open-label treatment in the group assigned to placebo (systolic: -7.9±2.90, diastolic -4.0±1.87 mmHg), whereas BP remained unchanged from the end of open-label in the group assigned to continue on ampreloxetine (systolic: 0.7±2.86 p=0.0303, diastolic: 0.9±1.85, p=0.0540).