Seproxetine, also known as (S)-norfluoxetine, is a selective serotonin reuptake inhibitor (SSRI).[1][2] It is the main active metabolite of the widely used antidepressant fluoxetine;[3] it is nearly 4 times more selective for stimulating neurosteroid synthesis relative to serotonin reuptake inhibition than fluoxetine.[4] It is formed through the demethylation, or removal of a methyl group, of fluoxetine.[5] Seproxetine is both an inhibitor of serotonin and dopamine transporters, 5-HT2A and 5-HT2C receptors.[6] It was being investigated by Eli Lilly and Company as an antidepressant; however, it causes cardiac arrhythmia by blocking the KvLQT1 protein, which is responsible for the management of the QT interval. This is the time it takes for the heart to contract and recover.[7] Due to this, development of the medication was discontinued.[1] Efficacy testing found that the drug was equivalent to fluoxetine, but sixteen times more powerful than the R enantiomer of norfluoxetine.[8]
References
- Seproxetine DrugBank, University of Alberta, retrieved 10 August 2016^
- Drug Interaction of Fluvoxamine and Fluoxetine with Nevirapine in HIV-1-Infected Individuals Clinical Drug Investigation, 2003-10-01^
- Guidelines for choice of selective serotonin reuptake inhibitor in depressive illness Advances in Psychiatric Treatment, 2001^
- SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake Current Opinion in Pharmacology, February 2009^
- Could fluorinated pharmaceuticals have an impact on the EOF amount in human blood? Örebro University, 2022^
- Solution, and solid investigations on the charge–transfer complexation between seproxetine as a selective serotonin reuptake inhibitor drug with six kinds of π–electron acceptors Journal of Molecular Liquids, 2021-06-15^
- Seproxetine Inxight Drugs, National Center for Advancing Translational Sciences (NCATS), retrieved 20 April 2023^
- An efficient synthesis of S-γ-[(4-trifluoromethyl)-phenoxy]benzenepropanamine-[1-14C] maleate, an important metabolite of fluoxetine hydrochloride Journal of Labelled Compounds and Radiopharmaceuticals, 1992^