Seproxetine

{{Short description|SSRI drug and metabolite of fluoxetine}}

{{Use dmy dates|date=August 2016}}{{Drugbox

| IUPAC_name = (S)-3-Phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine

| image = Seproxetine.svg

| image_class = skin-invert-image

| tradename =

| pregnancy_category =

| legal_status = Uncontrolled

| routes_of_administration =

| bioavailability =

| metabolism =

| elimination_half-life = 4–16 days

| excretion =

| CAS_number = 126924-38-7

| ATC_prefix = none

| ATC_suffix =

| PubChem = 4541

| IUPHAR_ligand = 208

| DrugBank = DB06731

| ChemSpiderID = 4382

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 25CO3X0R31

| C=16 | H=16 | F=3 | N=1 | O=1

}}

Seproxetine, also known as (S)-norfluoxetine, is a selective serotonin reuptake inhibitor (SSRI).{{cite web |title=Seproxetine |publisher=University of Alberta |url=http://www.drugbank.ca/drugs/DB06731 |access-date=10 August 2016 |language=en |archive-url=https://web.archive.org/web/20201031131203/https://go.drugbank.com/drugs/DB06731 |archive-date=October 31, 2020 |work=DrugBank}}{{cite journal | vauthors = de Maat MM, Huitema AD, Mulder JW, Meenhorst PL, van Gorp EC, Mairuhu AT, Beijnen JH | title = Drug Interaction of Fluvoxamine and Fluoxetine with Nevirapine in HIV-1-Infected Individuals | journal = Clinical Drug Investigation | volume = 23 | issue = 10 | pages = 629–637 | date = 2003-10-01 | pmid = 17535078 | doi = 10.2165/00044011-200323100-00002 | s2cid = 25958396 }} It is the S enantiomer of norfluoxetine, the main active metabolite of the widely used antidepressant fluoxetine;{{cite journal | vauthors = Anderson IM, Edwards JG |date=2001 |title=Guidelines for choice of selective serotonin reuptake inhibitor in depressive illness |journal=Advances in Psychiatric Treatment |language=en |volume=7 |issue=3 |pages=170–180 |doi=10.1192/apt.7.3.170 |issn=1355-5146|doi-access=free }} it is nearly 4 times more selective for stimulating neurosteroid synthesis relative to serotonin reuptake inhibition than fluoxetine.{{cite journal | vauthors = Pinna G, Costa E, Guidotti A | title = SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake | journal = Current Opinion in Pharmacology | volume = 9 | issue = 1 | pages = 24–30 | date = February 2009 | pmid = 19157982 | pmc = 2670606 | doi = 10.1016/j.coph.2008.12.006 }} It is formed through the demethylation, or removal of a methyl group, of fluoxetine.{{cite thesis | vauthors = Alvén Fimmerstad T | degree = degree of Bachelor |url=https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-100738 |title=Could fluorinated pharmaceuticals have an impact on the EOF amount in human blood? |date=2022 |publisher=Örebro University }} Seproxetine is both an inhibitor of serotonin and dopamine transporters, 5-HT_2A and 5-HT_2C receptors.{{cite journal | vauthors = Al-Humaidi JY, Refat MS |date=2021-06-15 |title=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 |url=https://www.sciencedirect.com/science/article/pii/S0167732221005560 |journal=Journal of Molecular Liquids |volume=332 |pages=115831 |doi=10.1016/j.molliq.2021.115831 |s2cid=233773168 |issn=0167-7322|url-access=subscription }} 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.{{cite web |title=Seproxetine |url=https://drugs.ncats.io/substance/25CO3X0R31 |url-status=live |archive-url=https://web.archive.org/web/20230420223550/https://drugs.ncats.io/substance/25CO3X0R31 |archive-date=April 20, 2023 |access-date=20 April 2023 |website=Inxight Drugs |publisher=National Center for Advancing Translational Sciences (NCATS)}} Due to this, development of the medication was discontinued. Tests on its efficacy found that it was equivalent to fluoxetine, but sixteen times more powerful than the R enantiomer of norfluoxetine.{{cite journal | vauthors = Wheeler WJ |date=1992 |title=An efficient synthesis of S-γ-[(4-trifluoromethyl)-phenoxy]benzenepropanamine-[1-14C] maleate, an important metabolite of fluoxetine hydrochloride |journal=Journal of Labelled Compounds and Radiopharmaceuticals |language=en |volume=31 |issue=2 |pages=119–124 |doi=10.1002/jlcr.2580310207}}