Page last updated: 2024-11-04

norfluoxetine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Norfluoxetine is a selective serotonin reuptake inhibitor (SSRI) that is a major metabolite of fluoxetine. It is a chiral compound and the (+) enantiomer has been found to be more potent than the (-) enantiomer. Norfluoxetine is thought to exert its effects by inhibiting the reuptake of serotonin in the central nervous system. This leads to an increase in serotonin levels in the synapse, which is thought to be responsible for its antidepressant effects. Norfluoxetine is also thought to be effective in treating other conditions, such as anxiety disorders, obsessive-compulsive disorder, and premenstrual dysphoric disorder. Research on norfluoxetine is ongoing, with interest in its potential therapeutic effects and its pharmacokinetic properties. As the major metabolite of the commonly prescribed SSRI fluoxetine, the investigation of norfluoxetine is important for understanding the effects and metabolism of fluoxetine. '

norfluoxetine: metabolite of fluoxetine; RN given refers to parent cpd without isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID4541
CHEMBL ID1494
CHEBI ID180876
SCHEMBL ID686500
MeSH IDM0110320

Synonyms (42)

Synonym
56161-73-0
3-phenyl-3-[4-(triluoromethyl)phenoxy]propan-1-amine
CHEBI:180876
gtpl208
nsc-675448
norfluoxetine
3-(4-trifluoromethylphenoxy)-3-phenylproplyamine
nsc675448
desmethylfluoxetine
83891-03-6
benzenepropanamine, gamma-[4-(trifluoromethyl)phenoxy]-
benzenepropanamine, gamma-[4-(trifluoromethyl)phenoxy]-, (+/-)-
benzenepropanamine, gamma-(4-(trifluoromethyl)phenoxy)-
gamma-(4-(trifluoromethyl)phenoxy)benzenepropanamine
CHEMBL1494
L001023
3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine
A840679
3-phenyl-3-(4-(trifluoromethyl)phenoxy)propan-1-amine
FT-0673087
FT-0673089
k8d70xe2f4 ,
unii-k8d70xe2f4
AKOS015911091
(+/-)-desmethylfluoxetine
benzenepropanamine, .gamma.-(4-(trifluoromethyl)phenoxy)-, (+/-)-
3-phenyl-3-(4-trifluoromethyl-phenoxy)-propylamine
SCHEMBL686500
3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine #
c16h16f3no
3-phenyl-3[4'-trifluoromethyl-phenoxy]-propan-1-amine
bdbm50180661
FT-0673088
DTXSID80866540
Q7452012
SB32682
SB32578
SB38941
norfluoxetine hcl;n-desmethylfluoxetine
BCP20944
(phenyl-d5)
benzenepropanamine, .gamma.-[4-(trifluoromethyl)phenoxy]-

Research Excerpts

Effects

ExcerptReferenceRelevance
"Norfluoxetine has been detected for the first time in sewage water and a preliminary analysis gave average concentrations of 150 and 225 ng/L for norfluoxetine and fluoxetine, respectively."( Hollow-fibre supported liquid membrane extraction for determination of fluoxetine and norfluoxetine concentration at ultra trace level in sewage samples.
Mårtensson, L; Mathiasson, L; Zorita, S, 2007
)
1.28

Actions

ExcerptReferenceRelevance
"The norfluoxetine C0 was 22% lower in elderly subjects (p < .05), with comparable decreases in AUC0-24 and Cmax."( Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers.
Harvey, AT; Preskorn, SH, 2001
)
0.79

Toxicity

ExcerptReferenceRelevance
" Therefore, we hypothesized that the high toxicity of aliphatic amines in algae is a toxicokinetic effect caused by speciation and not a toxicodynamic effect caused by a specific mode of toxic action."( The pH-dependent toxicity of basic pharmaceuticals in the green algae Scenedesmus vacuolatus can be explained with a toxicokinetic ion-trapping model.
Escher, BI; Neuwoehner, J, 2011
)
0.37
" However, investigation of their toxic effects on aquatic animals, single or in mixture with other occurring psychoactive drugs, has been neglected."( Norfluoxetine and venlafaxine in zebrafish larvae: Single and combined toxicity of two pharmaceutical products relevant for risk assessment.
Cunha, V; Ferreira, M; Guimarães, L; Oliva-Teles, L; Rodrigues, P, 2020
)
2

Pharmacokinetics

The aim of this study was to characterize extracellular level of serotonin (5-hydroxytryptamine, 5-HT)-time profile of norfluoxetine after acute administration over 18 h post dose. The pharmacokinetic data were gathered from several BA/BE studies conducted at Bangalore and Chennai, India.

ExcerptReferenceRelevance
" These results indicate that no pharmacokinetic interaction exists between triazolam and fluoxetine or norfluoxetine."( A pharmacokinetic evaluation of the combined administration of triazolam and fluoxetine.
Lasher-Sisson, TA; Steenwyk, RC; Swanson, CN; Wright, CE, 1992
)
0.5
"The pharmacokinetic and pharmacodynamic effects of concomitant administration of alprazolam and fluoxetine were studied in this double-blind parallel study in 80 healthy, male volunteers."( Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine.
Antal, EJ; Fleishaker, JC; Lasher, TA; Steenwyk, RC, 1991
)
0.28
" This study attempted to evaluate the pharmacokinetic and pharmacodynamic interactions between zolpidem 10 mg, a short-acting hypnotic, and fluoxetine 20 mg, an SSRI."( The effect of co-administration of zolpidem with fluoxetine: pharmacokinetics and pharmacodynamics.
Allard, S; Johnson, M; Piergies, AA; Roth-Schechter, BF; Sweet, J, 1996
)
0.29
" Further, the pharmacokinetic disposition and pharmacological activity of several highly bound drugs have been reported to be significantly altered as a result of elevated serum AAG."( Pharmacokinetics and antidepressant activity of fluoxetine in transgenic mice with elevated serum alpha-1-acid glycoprotein levels.
Dewey, MJ; Holladay, JW; Yoo, SD, 1998
)
0.3
"A sensitive, robust gas chromatographic-mass spectrometric assay suitable for use in pharmacokinetic or bioequivalence studies is presented for the selective serotonin reuptake inhibitor, fluoxetine, and its major metabolite, norfluoxetine (N-desmethylfluoxetine)."( Sensitive, high-throughput gas chromatographic-mass spectrometric assay for fluoxetine and norfluoxetine in human plasma and its application to pharmacokinetic studies.
Addison, RS; Franklin, ME; Hooper, WD, 1998
)
0.7
" Fluoxetine AUC0-24, C0, and Cmax did not differ in young and elderly subjects."( Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers.
Harvey, AT; Preskorn, SH, 2001
)
0.31
" The results showed small delays in peak concentration but no clinically significant effect of alosetron on the pharmacokinetics of S- and R-fluoxetine or S- and R-norfluoxetine."( Effect of alosetron on the pharmacokinetics of fluoxetine.
D'Souza, DL; Dimmitt, DC; Koch, KM; Nezamis, J; Robbins, DK; Simms, L, 2001
)
0.51
"The objective of this study was to evaluate the pharmacokinetic profile of fluoxetine (FLX) and its major metabolite, norfluoxetine (NORFLX), in children and adolescent patients undergoing psychiatric treatment."( Fluoxetine pharmacokinetics in pediatric patients.
Abrams, A; Biederman, J; Cohen, L; Faird, N; Neft, D; Sinha, V; Wilens, TE, 2002
)
0.52
" Coadministration of desloratadine with a potent inhibitor of CYP2D6 did not result in clinically relevant changes in its pharmacokinetic parameters."( Pharmacokinetics/pharmacodynamics of desloratadine and fluoxetine in healthy volunteers.
Banfield, C; Flannery, B; Gupta, S; Herron, J; Kantesaria, B, 2004
)
0.32
" The present study investigated potential modifications to the pharmacokinetic profile of milnacipran at steady-state when it is substituted for fluoxetine without any washout period."( Lack of pharmacokinetic interaction when switching from fluoxetine to milnacipran.
Chassard, D; Hermann, P; Puozzo, C, 2006
)
0.33
" The aim of this study was to characterize extracellular level of serotonin (5-hydroxytryptamine, 5-HT)-time profile of norfluoxetine after acute administration over 18 h post dose and to establish the relationship between this pharmacodynamic (PD) profile and its pharmacokinetic (PK) properties."( Pharmacokinetics and pharmacodynamics of norfluoxetine in rats: Increasing extracellular serotonin level in the frontal cortex.
Aluisio, L; Boggs, J; Hoey, K; Lord, B; Lovenberg, T; Mazur, C; Qu, Y, 2009
)
0.83
"The aim of the work was to retrospectively evaluate the pharmacokinetic data of fluoxetine and norfluoxetine from several bioavailability/bioequivalence (BA/BE) studies to identify the poor metabolizer (PM) phenotypes from the unsuspected healthy subjects across varied protocol designs, dose sizes and differing formulations."( Unsuspected poor metabolizer phenotypes of fluoxetine in bioavailability/bioequivalence studies from an indian population perspective. Retrospective pharmacokinetic data evaluation.
Kamath, N; Kandasamy, M; Kristjansson, F; Pai, B; Ravi, S; Srinivas, NR; Thangam, S; Tripathy, K, 2010
)
0.58
"The pharmacokinetic data of fluoxetine and norfluoxetine were gathered from several BA/BE studies conducted at clinical facilities located at Bangalore and Chennai, India."( Unsuspected poor metabolizer phenotypes of fluoxetine in bioavailability/bioequivalence studies from an indian population perspective. Retrospective pharmacokinetic data evaluation.
Kamath, N; Kandasamy, M; Kristjansson, F; Pai, B; Ravi, S; Srinivas, NR; Thangam, S; Tripathy, K, 2010
)
0.62
"Retrospective evaluation of fluoxetine and norfluoxetine pharmacokinetic data demonstrated existence of both PM and EM phenotypes in the Indian population."( Unsuspected poor metabolizer phenotypes of fluoxetine in bioavailability/bioequivalence studies from an indian population perspective. Retrospective pharmacokinetic data evaluation.
Kamath, N; Kandasamy, M; Kristjansson, F; Pai, B; Ravi, S; Srinivas, NR; Thangam, S; Tripathy, K, 2010
)
0.62
" In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats."( Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.
Garcia, P; Höcht, C; Laino, CH; Podestá, MF; Reinés, A; Slobodianik, N, 2014
)
0.4
" Accordingly, pharmacokinetic analysis of a series of fluoxetine and norfluoxetine administrations to pregnant baboons was performed."( Pharmacokinetics of fluoxetine in pregnant baboons (Papio spp.).
Garland, M; Shoulson, RL; Stark, RL, 2014
)
0.64
"Serial sampling methods have been used for rat pharmacokinetic (PK) studies for over 20 years."( Utility of capillary microsampling for rat pharmacokinetic studies: Comparison of tail-vein bleed to jugular vein cannula sampling.
Guo, Y; Ho, S; Korfmacher, W; Luo, Y; O'Shea, T; Shen, L; Snow, G; Sun, W; Wang, J; Wu, Z,
)
0.13
" A physiologically based pharmacokinetic model for fluoxetine and norfluoxetine metabolism was developed to predict and investigate changes in concentration-time profiles according to fluoxetine dosage in the Korean population."( Prediction of Fluoxetine and Norfluoxetine Pharmacokinetic Profiles Using Physiologically Based Pharmacokinetic Modeling.
Chae, YJ; Jeong, HC; Kang, W; Lee, S; Shin, KH; Yun, HY, 2021
)
1.15

Compound-Compound Interactions

A three-phase, liquid-phase microextraction using a hollow fibre (HF-LPME) combined with high performance liquid chromatography-fluorescence detection (HPLC-FL) was developed for the analysis of fluoxetine (FLX) and its active metabolite, norfluoxetin (NFLX) in human plasma.

ExcerptReferenceRelevance
"A three-phase, liquid-phase microextraction using a hollow fibre (HF-LPME) combined with high performance liquid chromatography-fluorescence detection (HPLC-FL) was developed for the analysis of fluoxetine (FLX) and its active metabolite, norfluoxetine (NFLX), in human plasma."( Three-phase, liquid-phase microextraction combined with high performance liquid chromatography-fluorescence detection for the simultaneous determination of fluoxetine and norfluoxetine in human plasma.
de Freitas, DF; de Siqueira, ME; Porto, CE; Vieira, EP, 2010
)
0.74
" This observed discrepancy between in vitro risk assessment and in vivo drug-drug interaction (DDI) profile was rationalized by time-varying dynamic pharmacokinetic models that incorporated circulating concentrations of fluoxetine and norfluoxetine enantiomers, mutual inhibitor-inhibitor interactions, and CYP3A4 induction."( Fluoxetine- and norfluoxetine-mediated complex drug-drug interactions: in vitro to in vivo correlation of effects on CYP2D6, CYP2C19, and CYP3A4.
Davis, C; Foti, RS; Isoherranen, N; Kunze, KL; Lutz, JD; Sager, JE, 2014
)
0.93

Bioavailability

ExcerptReferenceRelevance
" At the lowest dose tested (5 mg/kg) the drug was efficiently extracted by the liver (extraction ratio about 60%), resulting in bioavailability of only about 38%."( Influence of dose and route of administration on the kinetics of fluoxetine and its metabolite norfluoxetine in the rat.
Caccia, S; Cappi, M; Fracasso, C; Garattini, S, 1990
)
0.5
" The three experiments taken together suggest that the complexation of fluoxetine HCl into gamma-cyclodextrin increases its pharmacological efficacy in animals, this effect being related to an enhancement of its oral bioavailability as demonstrated in human healthy subjects."( The inclusion of fluoxetine into gamma-cyclodextrin increases its bioavailability: behavioral, electrophysiological and pharmacokinetic studies.
Bruhwyler, J; Decamp, E; Dresse, A; Géczy, J; Lejeune, C; Liégeois, JF; Masset, H; Scuvée-Moreau, J; Seutin, V; Szejtli, J; Szente, L; Van Heugen, JC, 2000
)
0.31
" Relative bioavailability of each dose administered via the TD route was 10% of the value for oral administration of the drug."( Comparative bioavailability of fluoxetine after transdermal and oral administration to healthy cats.
Ciribassi, J; Kaloostian-Whittymore, L; Luescher, A; Pasloske, KS; Robertson-Plouch, C; Zimmerman, A, 2003
)
0.32
" However, the relative bioavailability for TD administration is approximately only 10% of that for the oral route of administration."( Comparative bioavailability of fluoxetine after transdermal and oral administration to healthy cats.
Ciribassi, J; Kaloostian-Whittymore, L; Luescher, A; Pasloske, KS; Robertson-Plouch, C; Zimmerman, A, 2003
)
0.32
"This study was conducted to determine the relative rectal bioavailability of fluoxetine capsules as well as the acceptability of the rectal route of fluoxetine capsule administration."( Relative rectal bioavailability of fluoxetine in normal volunteers.
Cameron, OG; Guthrie, SK; Phan, KL; Teter, CJ, 2005
)
0.33
"The pharmacokinetics and relative bioavailability of fluoxetine capsules (reference) and tablets (test) were compared in 24 healthy subjects of both sexes after a single 20 mg oral dose of fluoxetine (as a hydrochloride salt)."( Bioequivalence testing of a new tablet formulation of generic fluoxetine.
Dordević, S; Jovanović, D; Jovanović, M; Jovic-Stosić, J; Kilibarda, V; Knezević, T; Srdić, D,
)
0.13
"The aim of this study was to compare the bioavailability and tolerability of the proposed generic formulation with the established reference formulation of fluoxetine hydrochloride 20 mg in a fasting, healthy Chinese male population."( Comparative bioavailability and tolerability of a single 20-mg dose of two fluoxetine hydrochloride dispersible tablet formulations in fasting, healthy Chinese male volunteers: an open-label, randomized-sequence, two-period crossover study.
Li, Z; Liu, Y; Shi, S; Wu, J; Zeng, F; Zhao, Y; Zhong, D, 2010
)
0.36
" cancer, but bioavailability was low."( Toxicokinetics, disposition and metabolism of fluoxetine in crabs.
Hucher, N; Knigge, T; Monsinjon, T; Robert, A; Schultz, IR, 2017
)
0.46
"Few studies have focused on the influence of environmental conditions on the bioavailability of pollutants interacted with nanomaterials in organisms."( Comparison of the accumulation and metabolite of fluoxetine in zebrafish larva under different environmental conditions with or without carbon nanotubes.
Bao, X; Ji, Y; Jiang, R; Liu, J; Lu, G; Sun, H; Yan, Z, 2019
)
0.51

Dosage Studied

A physiologically based pharmacokinetic model was developed to predict and investigate changes in concentration-time profiles according to fluoxetine dosage in the Korean population. Blood samples were collected for at least 672 h after fluoxeine dosing and the plasma was analyzed using validated tandem liquid chromatography mass spectrometric assay.

ExcerptRelevanceReference
" When imipramine or desipramine are to be coadministered with fluoxetine, a lower dosage may be needed to maintain steady-state concentrations and to avoid undesirable side effects caused by excessive tricyclic concentrations."( Quantification and mechanism of the fluoxetine and tricyclic antidepressant interaction.
Bergstrom, RF; Lemberger, L; Peyton, AL, 1992
)
0.28
" A subchronic study in severe seizure GEPRs demonstrated that the ED50 after 28 days of dosing (8."( Effects of fluoxetine on convulsions and on brain serotonin as detected by microdialysis in genetically epilepsy-prone rats.
Burger, RL; Dailey, JW; Jobe, PC; Mishra, PK; Yan, QS, 1992
)
0.28
" Thus, at steady state both fluoxetine and norfluoxetine concentrations will be higher in patients with cirrhosis, unless the dosage is reduced."( Fluoxetine disposition and elimination in cirrhosis.
Bergstrom, RF; Lemberger, L; Schenker, S; Wolen, RL, 1988
)
0.54
" Blood samples for the measurement of fluoxetine and its active metabolite norfluoxetine were drawn 13 times in the first 48 hr after dosing and thrice weekly thereafter for 4 wk."( Fluoxetine kinetics and protein binding in normal and impaired renal function.
Aronoff, GR; Bergstrom, RF; Lemberger, L; Pottratz, ST; Sloan, RS; Wolen, RL, 1984
)
0.5
" With a few exceptions, the cumulative dosage of FLU and the AUC of FLU and NFLU were better predictors of the changes in awake and movement time in the PSG than single-sample concentrations of FLU and NFLU taken at the time of PSG assessment."( The effects of fluoxetine on the polysomnogram of depressed outpatients: a pilot study.
Armitage, R; Battaglia, J; Cain, JW; Debus, JR; Grannemann, BD; Hendrickse, WA; Orsulak, PJ; Roffwarg, HP; Rush, AJ, 1994
)
0.29
"This study explored serum concentrations of fluoxetine and norfluoxetine in subjects treated under different dosing regimens."( Fluoxetine and norfluoxetine serum concentrations and clinical response in weekly versus daily dosing.
Burke, WJ; Hendricks, SE; Jacques, D; McArthur-Campbell, D; Stull, T, 1996
)
0.89
" A significant, non-parallel shift in the dose-response curve of serotonergic neurons to the serotonin-1A (5-HT1A) agonist 8-OH-DPAT occurred over the 21 days of treatment with fluoxetine, indicating a desensitization of the 5-HT1A receptor during this period."( Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal raphe nucleus of the rat.
Czachura, JF; Rasmussen, K, 2000
)
0.31
" Fluoxetine dosing inhibited CYP2C19 activity in both age groups, increasing the (S)- to (R)-mephenytoin ratio 3- to 4-fold (p < ."( Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers.
Harvey, AT; Preskorn, SH, 2001
)
0.31
" Peak breast milk concentrations occurred approximately 8 hours after maternal dosing and predicted norfluoxetine concentrations in infant serum."( Fluoxetine and norfluoxetine concentrations in nursing infants and breast milk.
Altshuler, LL; Fukuchi, A; Hendrick, V; Hostetter, A; Hwang, S; Leight, K; Mintz, J; Stowe, ZN; Suri, R, 2001
)
0.88
" A comparison of citalopram and fluoxetine pharmacokinetics in the same animal and at the same dosage (1 mg/kg) showed that citalopram SERT occupancy and plasma half-lives were 9 times and 14 times shorter, respectively, than those of fluoxetine and norfluoxetine."( [11C]-DASB, a tool for in vivo measurement of SSRI-induced occupancy of the serotonin transporter: PET characterization and evaluation in cats.
Ginovart, N; Houle, S; Hussey, D; Meyer, JH; Wilson, AA, 2003
)
0.5
" Fluoxetine in a formulation of pluronic lecithin organogel (PLO gel) was applied to the hairless portion of the pinnae of cats at 2 dosages (5 or 10 mg/kg), or it was administered orally in capsules at a dosage of 1 mg/kg."( Comparative bioavailability of fluoxetine after transdermal and oral administration to healthy cats.
Ciribassi, J; Kaloostian-Whittymore, L; Luescher, A; Pasloske, KS; Robertson-Plouch, C; Zimmerman, A, 2003
)
0.32
"We have previously reported that repeated dosing with the selective serotonin reuptake inhibitor (SSRI) citalopram decreases striatal [11C]raclopride binding in healthy volunteers."( Effects of fluoxetine on dopamine D2 receptors in the human brain: a positron emission tomography study with [11C]raclopride.
Aalto, S; Hietala, J; Hirvonen, J; Ilonen, T; Kajander, J; Någren, K; Penttilä, J; Syvälahti, E, 2004
)
0.32
" Serum samples, obtained before dosing and at various appropriate time points up to 192 hours, were analyzed for fluoxetine and norfluoxetine content by a simple, accurate and precise HPLC method."( Bioequivalence testing of a new tablet formulation of generic fluoxetine.
Dordević, S; Jovanović, D; Jovanović, M; Jovic-Stosić, J; Kilibarda, V; Knezević, T; Srdić, D,
)
0.34
" Therefore, rat urine taken after dosing with fluoxetine was screened in the same way."( Gas chromatography-mass spectrometry detection of a norfluoxetine artifact in hydrolyzed urine samples may falsely indicate tranylcypromine ingestion.
Maurer, HH; Meyer, MR; Schwaninger, AE,
)
0.38
" Blood samples were collected for at least 672 h after fluoxetine dosing and the plasma was analyzed using validated tandem liquid chromatography mass spectrometric assay to determine fluoxetine and norfluoxetine levels."( Unsuspected poor metabolizer phenotypes of fluoxetine in bioavailability/bioequivalence studies from an indian population perspective. Retrospective pharmacokinetic data evaluation.
Kamath, N; Kandasamy, M; Kristjansson, F; Pai, B; Ravi, S; Srinivas, NR; Thangam, S; Tripathy, K, 2010
)
0.55
" These data may inform treatment decisions related to dosing in patients who receive fluoxetine during pregnancy."( Disposition of chiral and racemic fluoxetine and norfluoxetine across childbearing.
Helsel, JC; Luther, JF; Perel, JM; Sit, D; Wisner, KL; Wisniewski, SR, 2010
)
0.62
" High inter-individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found."( Therapeutic drug monitoring of children and adolescents treated with fluoxetine.
Burger, R; Egberts, K; Fegert, JM; Gerlach, M; Kliegl, K; Koelch, M; Ludolph, AG; Mehler-Wex, C; Pfalzer, AK; Rothenhöfer, S; Stingl, J; Taurines, R, 2012
)
0.38
" Our results also are applicable to determining appropriate dosing of nonhuman primates in clinical settings."( Pharmacokinetics of fluoxetine in pregnant baboons (Papio spp.).
Garland, M; Shoulson, RL; Stark, RL, 2014
)
0.4
"In this report, five compounds were dosed orally into rats."( Utility of capillary microsampling for rat pharmacokinetic studies: Comparison of tail-vein bleed to jugular vein cannula sampling.
Guo, Y; Ho, S; Korfmacher, W; Luo, Y; O'Shea, T; Shen, L; Snow, G; Sun, W; Wang, J; Wu, Z,
)
0.13
" Median effective dose was interpolated from the triplicated experiments and the dose-response curves were generated for each drug-virus combination."( A preclinical assessment to repurpose drugs to target type 1 diabetes-associated type B coxsackieviruses.
Honkimaa, A; Hyöty, H; Sioofy-Khojine, AB, 2020
)
0.56
" A physiologically based pharmacokinetic model for fluoxetine and norfluoxetine metabolism was developed to predict and investigate changes in concentration-time profiles according to fluoxetine dosage in the Korean population."( Prediction of Fluoxetine and Norfluoxetine Pharmacokinetic Profiles Using Physiologically Based Pharmacokinetic Modeling.
Chae, YJ; Jeong, HC; Kang, W; Lee, S; Shin, KH; Yun, HY, 2021
)
1.15
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
(trifluoromethyl)benzenesAn organofluorine compound that is (trifluoromethyl)benzene and derivatives arising from substitution of one or more of the phenyl hydrogens.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (2)

PathwayProteinsCompounds
Fluoxetine Action Pathway3618
Fluoxetine Metabolism Pathway69

Protein Targets (4)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium channel subfamily K member 2Homo sapiens (human)IC50 (µMol)9.00000.40003.92279.0000AID1307725
Sodium channel protein type 1 subunit alphaRattus norvegicus (Norway rat)IC50 (µMol)0.80000.01001.14052.9390AID726266
Potassium voltage-gated channel subfamily C member 1Rattus norvegicus (Norway rat)IC50 (µMol)0.80000.80000.80000.8000AID726266
Potassium voltage-gated channel subfamily H member 2Homo sapiens (human)IC50 (µMol)2.29090.00091.901410.0000AID576612
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (33)

Processvia Protein(s)Taxonomy
cardiac ventricle developmentPotassium channel subfamily K member 2Homo sapiens (human)
G protein-coupled receptor signaling pathwayPotassium channel subfamily K member 2Homo sapiens (human)
memoryPotassium channel subfamily K member 2Homo sapiens (human)
response to mechanical stimulusPotassium channel subfamily K member 2Homo sapiens (human)
response to axon injuryPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of cardiac muscle cell proliferationPotassium channel subfamily K member 2Homo sapiens (human)
cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium channel subfamily K member 2Homo sapiens (human)
cochlea developmentPotassium channel subfamily K member 2Homo sapiens (human)
positive regulation of cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of DNA biosynthetic processPotassium channel subfamily K member 2Homo sapiens (human)
stabilization of membrane potentialPotassium channel subfamily K member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by hormonePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of DNA-templated transcriptionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion homeostasisPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cardiac muscle contractionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of ventricular cardiac muscle cell membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cellular response to xenobiotic stimulusPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane depolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of heart rate by cardiac conductionPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
membrane repolarization during ventricular cardiac muscle cell action potentialPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
positive regulation of potassium ion transmembrane transportPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
negative regulation of potassium ion export across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
potassium ion import across plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (14)

Processvia Protein(s)Taxonomy
outward rectifier potassium channel activityPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion leak channel activityPotassium channel subfamily K member 2Homo sapiens (human)
transcription cis-regulatory region bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
delayed rectifier potassium channel activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
ubiquitin protein ligase bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
identical protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
protein homodimerization activityPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
C3HC4-type RING finger domain bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
scaffold protein bindingPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarizationPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (10)

Processvia Protein(s)Taxonomy
endoplasmic reticulum membranePotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
cell surfacePotassium channel subfamily K member 2Homo sapiens (human)
apical plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
neuronal cell bodyPotassium channel subfamily K member 2Homo sapiens (human)
calyx of HeldPotassium channel subfamily K member 2Homo sapiens (human)
astrocyte projectionPotassium channel subfamily K member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
cell surfacePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
perinuclear region of cytoplasmPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
inward rectifier potassium channel complexPotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
plasma membranePotassium voltage-gated channel subfamily H member 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (13)

Assay IDTitleYearJournalArticle
AID1307725Inhibition of of human TREK1 expressed in tsA201 cells assessed as reduction in channel currents2016Journal of medicinal chemistry, 06-09, Volume: 59, Issue:11
Perspectives on the Two-Pore Domain Potassium Channel TREK-1 (TWIK-Related K(+) Channel 1). A Novel Therapeutic Target?
AID311933Inhibition of ASM in rat PC12 cells assessed as residual activity at 10 uM2008Journal of medicinal chemistry, Jan-24, Volume: 51, Issue:2
Identification of new functional inhibitors of acid sphingomyelinase using a structure-property-activity relation model.
AID576612Inhibition of human ERG2011European journal of medicinal chemistry, Feb, Volume: 46, Issue:2
Predicting hERG activities of compounds from their 3D structures: development and evaluation of a global descriptors based QSAR model.
AID1597723Half life in human2019Bioorganic & medicinal chemistry letters, 08-15, Volume: 29, Issue:16
Sleep modulating agents.
AID681144TP_TRANSPORTER: cell accumulation of calcein in L-MDR1 cells2003The Journal of pharmacology and experimental therapeutics, Apr, Volume: 305, Issue:1
Inhibition of P-glycoprotein by newer antidepressants.
AID726266Inhibition of rat voltage-gated K channel 3.1 expressed in CHO cells by patch clamp assay2013Journal of medicinal chemistry, Feb-14, Volume: 56, Issue:3
Ion channels as therapeutic targets: a drug discovery perspective.
AID624222Antagonists at Rat 5-Hydroxytryptamine receptor 5-HT2A2000Circulation, Dec-05, Volume: 102, Issue:23
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.
AID1346662Rat Kv3.1 (Voltage-gated potassium channels)2001Neuropharmacology, Sep, Volume: 41, Issue:4
Effects of norfluoxetine, the major metabolite of fluoxetine, on the cloned neuronal potassium channel Kv3.1.
AID624218Antagonists at Human 5-Hydroxytryptamine receptor 5-HT2B2000Circulation, Dec-05, Volume: 102, Issue:23
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.
AID1346919Rat 5-HT2A receptor (5-Hydroxytryptamine receptors)2000Circulation, Dec-05, Volume: 102, Issue:23
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.
AID1346604Human K2P2.1 (Two P domain potassium channels)2005British journal of pharmacology, Mar, Volume: 144, Issue:6
Inhibition of the human two-pore domain potassium channel, TREK-1, by fluoxetine and its metabolite norfluoxetine.
AID1346867Human 5-HT2B receptor (5-Hydroxytryptamine receptors)2000Circulation, Dec-05, Volume: 102, Issue:23
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.
AID1346868Rat 5-HT2C receptor (5-Hydroxytryptamine receptors)2000Circulation, Dec-05, Volume: 102, Issue:23
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (267)

TimeframeStudies, This Drug (%)All Drugs %
pre-19909 (3.37)18.7374
1990's89 (33.33)18.2507
2000's94 (35.21)29.6817
2010's63 (23.60)24.3611
2020's12 (4.49)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 45.94

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index45.94 (24.57)
Research Supply Index5.73 (2.92)
Research Growth Index5.46 (4.65)
Search Engine Demand Index69.47 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (45.94)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials33 (12.00%)5.53%
Reviews8 (2.91%)6.00%
Case Studies11 (4.00%)4.05%
Observational0 (0.00%)0.25%
Other223 (81.09%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]