Seproxetine, also known as (S)-norfluoxetine, is a
selective serotonin reuptake inhibitor (SSRI).[1][2] It is the Senantiomer of norfluoxetine, the main
active metabolite of the widely used
antidepressantfluoxetine;[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 norfluoxetine.[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 inhibited 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. Due to the inhibition, the QT interval was prolonged, which could lead to significant cardiac side complications.[7] Due to this,
development of the medication was discontinued.[1] Tests on its efficacy found that it was equivalent to fluoxetine, but sixteen times more powerful than the R enantiomer of norfluoxetine.[8]
References
^
ab"Seproxetine". DrugBank. University of Alberta. Archived from
the original on 31 October 2020. Retrieved 10 August 2016.
^de Maat MM, Huitema AD, Mulder JW, Meenhorst PL, van Gorp EC, Mairuhu AT, Beijnen JH (1 October 2003). "Drug Interaction of Fluvoxamine and Fluoxetine with Nevirapine in HIV-1-Infected Individuals". Clinical Drug Investigation. 23 (10): 629–637.
doi:
10.2165/00044011-200323100-00002.
PMID17535078.
S2CID25958396.
^"Seproxetine". Inxight Drugs. National Center for Advancing Translational Sciences (NCATS).
Archived from the original on 20 April 2023. Retrieved 20 April 2023.
^Wheeler WJ (1992). "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. 31 (2): 119–124.
doi:
10.1002/jlcr.2580310207.