54739-18-3 CJOFXWAVKWHTFT-XSFVSMFZSA-N CJOFXWAVKWHTFT-XSFVSMFZSA-N Fluvoxamine 1-Pentanone, 5-methoxy-1-[4-(trifluoromethyl)phenyl]-, O-(2-aminoethyl)oxime, (1E)- DTXSID2044002 PR:000015189 PR sodium-dependent serotonin transporter GO:0098810 GO neurotransmitter reuptake GO:0051610 GO serotonin uptake GO:0001820 GO serotonin secretion NBO:0000018 NBO fear/anxiety related behavior MP:0014039 MP abnormal sheltering behavior GO:0002120 GO predatory behavior 2 WIKI decreased 1 WIKI increased Fluoxetine 2016-11-29T18:42:27 2016-11-29T18:42:27 Fluvoxamine 2016-11-29T18:42:27 2016-11-29T18:42:27 WikiUser_26 ApacheUser rodents WikiUser_6 ApacheUser fish WCS_90988 common ecological species Pimephales promelas 52640 NCBI Echinogammarus marinus Inhibition, 5-hydroxytryptamine transporter (5-HTT; SERT) Molecular <p>Inhibitors of the serotonin reuptake transporter (SERT; 5-hydroxytryptamine transporter; 5-HTT) block the reuptake of the neurotransmitter serotonin, increasing its residence time in synapses&nbsp;<em>(McDonald 2017; Correira et al. 2023). &nbsp;Selective serotonin reuptake inhibitor (SSRI) antidepressants are a class of compounds known to inhibit serotonin reuptake transporter activity (McDonald 2017).</em></p> <ul> <li>Toxcast assays that target the serotonin transporter (5-HTT; SERT) gene SLC6A4 include: NVS_TR_rSERT,NVS_TR_rSERT.&nbsp;&nbsp;</li> <li><em>SERT activity can be measured by the rate of uptake of radiolabeled compounds into cells, with development of fluorescent dyes a recent development (Persson et al. 2023). &nbsp;</em></li> <li><em>Real time PCR can be used to measure transcript abundance of genes for SERT, which is an indirect &ndash; and only semi-quantitative indicator of protein abundance. &nbsp;</em><em>&nbsp;</em></li> <li><em>Serotonin concentrations can be measured via microdialysis/high-performance liquid chromatography, fast-scan cyclic voltammetry, N-Shaped Multiple Cyclic Square Wave Voltammetry, and Fast-Scan Controlled-Adsorption Voltammetry (Rojas Cabrera et al. 2023).</em></li> </ul> <p><em>Life Stage: Applies to all life stages with developed brain and central nervous systems.</em></p> <p><br /> <em>Sex: Applies to both males and females.</em></p> <p><br /> <em>Taxonomic: Primarily studied in laboratory rodents, humans, and fish.</em><br /> &nbsp;</p> CL:0000100 CL motor neuron High Unspecific Moderate All life stages High High <p><em>Correia, D., Domingues, I., Faria, M., and Oliveira, M. &nbsp;2023. &nbsp;Effects of fluoxetine on fish: What do we know and where should we focus our efforts in the future? &nbsp;Science of the Total Environment 857: 159486.</em></p> <p><br /> <em>McDonald, M.D. &nbsp;2017. &nbsp;An AOP analysis of selective serotonin reuptake inhibitors (SSRIs) for fish. Comparative Biochemistry and Physiology, Part C-Toxicology and Pharmacology 197: 19&ndash;31.</em></p> <p><br /> <em>Persson, M., Vikingsson, S., Kronstrand, R., and Green, H. 2023. &nbsp;Characterization of neurotransmitter inhibition for seven cathinones by a proprietary fluorescent dye method. Drug Testing and Analysis 16(4): 339-347.</em></p> <p><br /> <em>Rojas Cabrera, J.M., Oesterle, T.S., Rusheen, A.E., Goyal, A., Scheitler, K.M., Mandybur, I., Blaha, C.D., Bennet, K.E., Heien, M.L., Jang, D.P., Lee, K.H., Oh, Y., and Shin, H. 2023. Techniques for Measurement of Serotonin: Implications in Neuropsychiatric Disorders and Advances in Absolute Value Recording Methods. ACS Chemical Neuroscience 14(24): 4264-4273.</em></p> <p><br /> <em>NOTE: Italics indicate edits from John Frisch January 2025.</em><br /> &nbsp;</p> AOPWiki 2016-11-29T18:41:25 2025-02-24T08:34:09 Increased, serotonin (5-HT) Cellular <p>Increased concentration of serotonin in neuronal junctions either due to increased release of serotonin or diminished reuptake.</p> CL:0000100 CL motor neuron AOPWiki 2016-11-29T18:41:25 2017-09-16T10:15:52 Decreased, anxiety Individual AOPWiki 2016-11-29T18:41:25 2016-12-03T16:37:50 Decreased, sheltering Individual AOPWiki 2016-11-29T18:41:25 2016-12-03T16:37:50 Increased, predation Population AOPWiki 2016-11-29T18:41:25 2016-12-03T16:37:50 AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:58 AOPWiki 2016-11-29T18:41:34 2016-12-03T16:37:59 5-HTT block to incr. predation Ksenia Groh <p>Bryan Brooks, Baylor University, USA</p> <p>Kellie Fay, US EPA</p> <p>Ksenia Groh, EAWAG, Switzerland</p> BY-SA 1.0 adjacent Not Specified Not Specified non-adjacent Not Specified Not Specified non-adjacent Not Specified Not Specified non-adjacent Not Specified Not Specified Not Specified Not Specified <p>This putative AOP is based on a few studies in fish and mollusks and should be considered preliminary only.</p> AOPWiki 2016-11-29T18:41:16 2026-01-11T16:56:07