Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.

Autor:	Mwesigwa N; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (N.M., C.A.S.)., Shibao CA; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (N.M., C.A.S.).
Jazyk:	angličtina
Zdroj:	Hypertension (Dallas, Tex. : 1979) [Hypertension] 2024 Jul; Vol. 81 (7), pp. 1460-1466. Date of Electronic Publication: 2024 May 20.
DOI:	10.1161/HYPERTENSIONAHA.124.22069
Abstrakt:	The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI. Competing Interests: Disclosures C.A. Shibao has received a research grant from the Doris Duke Foundation. C.A. Shibao received grant support from the Office of Orphan Products Development. Food and Drug Administration, grant No. FD-R-04778-01-A3. C.A. Shibao has received a speaker honorarium from Lundbeck Pharmaceuticals. C.A. Shibao is the principal investigator of the trial funded by Theravance Biopharma. The other author reports no conflicts.
Databáze:	MEDLINE
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