Ampreloxetine

A norepinephrine reuptake inhibitor

{{Drugbox | verifiedfields = changed | verifiedrevid = 477002123

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Chemical structure of ampreloxetine

| image2 = | IUPAC_name = (1R,2R)-2-[(2-{[2-(2,3-dihydro-1H-inden-2-yl)ethyl]amino}ethyl)amino]-1-phenylethanol | tradename = | legal_status = Investigational | routes_of_administration = Oral | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number = 123456-78-9 | ATC_prefix = | ATC_suffix = | PubChem = 12345678 | DrugBank = | ChemSpiderID = 123456 | UNII = | KEGG = | ChEBI = | ChEMBL = | synonyms = TD-9855 }}

Ampreloxetine is a norepinephrine reuptake inhibitor (NRI) that is being investigated for the treatment of neurogenic orthostatic hypotension (nOH). It is a selective inhibitor of the norepinephrine transporter, which increases the levels of norepinephrine in the synaptic cleft and enhances sympathetic nervous system activity.

Mechanism of Action

Ampreloxetine works by inhibiting the reuptake of norepinephrine (NE) into presynaptic neurons. This action increases the concentration of norepinephrine in the synaptic cleft, thereby enhancing adrenergic signaling. The increased norepinephrine levels lead to vasoconstriction and an increase in blood pressure, which is beneficial in conditions like neurogenic orthostatic hypotension where blood pressure regulation is impaired.

Clinical Development

Ampreloxetine is currently in clinical trials for the treatment of neurogenic orthostatic hypotension, a condition characterized by a significant drop in blood pressure upon standing, leading to dizziness and fainting. The drug is being developed by Theravance Biopharma and has shown promise in early-phase clinical trials.

Pharmacokinetics

The pharmacokinetic profile of ampreloxetine includes oral administration, with studies indicating a favorable absorption and distribution profile. The elimination half-life of ampreloxetine allows for once-daily dosing, which is advantageous for patient compliance.

Potential Side Effects

As with other norepinephrine reuptake inhibitors, potential side effects of ampreloxetine may include increased heart rate, hypertension, and insomnia. These effects are due to the increased adrenergic activity resulting from higher norepinephrine levels.

Research and Future Directions

Research is ongoing to determine the long-term efficacy and safety of ampreloxetine in patients with neurogenic orthostatic hypotension. Future studies may explore its use in other conditions associated with dysregulated norepinephrine levels.

Related Pages

• Norepinephrine reuptake inhibitor
• Neurogenic orthostatic hypotension
• Adrenergic system