Recent Advances and Challenges of the Drugs Acting on Monoamine Transporters

Author(s): Weiwei Xue*, Tingting Fu, Guoxun Zheng, Gao Tu, Yang Zhang, Fengyuan Yang, Lin Tao, Lixia Yao, Feng Zhu*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 23 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Background: The human Monoamine Transporters (hMATs), primarily including hSERT, hNET and hDAT, are important targets for the treatment of depression and other behavioral disorders with more than the availability of 30 approved drugs.

Objective: This paper is to review the recent progress in the binding mode and inhibitory mechanism of hMATs inhibitors with the central or allosteric binding sites, for the benefit of future hMATs inhibitor design and discovery. The Structure-Activity Relationship (SAR) and the selectivity for hit/lead compounds to hMATs that are evaluated by in vitro and in vivo experiments will be highlighted.

Methods: PubMed and Web of Science databases were searched for protein-ligand interaction, novel inhibitors design and synthesis studies related to hMATs.

Results: Literature data indicate that since the first crystal structure determinations of the homologous bacterial Leucine Transporter (LeuT) complexed with clomipramine, a sizable database of over 100 experimental structures or computational models has been accumulated that now defines a substantial degree of structural variability hMATs-ligands recognition. In the meanwhile, a number of novel hMATs inhibitors have been discovered by medicinal chemistry with significant help from computational models.

Conclusion: The reported new compounds act on hMATs as well as the structures of the transporters complexed with diverse ligands by either experiment or computational modeling have shed light on the poly-pharmacology, multimodal and allosteric regulation of the drugs to transporters. All of the studies will greatly promote the Structure-Based Drug Design (SBDD) of structurally novel scaffolds with high activity and selectivity for hMATs.

Keywords: Monoamine transporters, allosteric modulation, multi-target drug, common binding mode, drug selectivity, computational modeling, structure activity analysis.

[1]
Kristensen, A.S.; Andersen, J.; Jørgensen, T.N.; Sørensen, L.; Eriksen, J.; Loland, C.J.; Strømgaard, K.; Gether, U. SLC6 neurotransmitter transporters: structure, function, and regulation. Pharmacol. Rev., 2011, 63(3), 585-640.
[http://dx.doi.org/10.1124/pr.108.000869] [PMID: 21752877]
[2]
Zhu, F.; Han, B.; Kumar, P.; Liu, X.; Ma, X.; Wei, X.; Huang, L.; Guo, Y.; Han, L.; Zheng, C.; Chen, Y. Update of TTD: therapeutic target database. Nucleic Acids Res., 2010, 38(Database issue), D787-D791.
[http://dx.doi.org/10.1093/nar/gkp1014] [PMID: 19933260]
[3]
Pramod, A.B.; Foster, J.; Carvelli, L.; Henry, L.K. SLC6 transporters: structure, function, regulation, disease association and therapeutics. Mol. Aspects Med., 2013, 34(2-3), 197-219.
[http://dx.doi.org/10.1016/j.mam.2012.07.002] [PMID: 23506866]
[4]
Manepalli, S.; Surratt, C.K.; Madura, J.D.; Nolan, T.L. Monoamine transporter structure, function, dynamics, and drug discovery: a computational perspective. AAPS J., 2012, 14(4), 820-831.
[http://dx.doi.org/10.1208/s12248-012-9391-0] [PMID: 22918625]
[5]
Zhu, F.; Shi, Z.; Qin, C.; Tao, L.; Liu, X.; Xu, F.; Zhang, L.; Song, Y.; Liu, X.; Zhang, J.; Han, B.; Zhang, P.; Chen, Y. Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res., 2012, 40(Database issue), D1128-D1136.
[http://dx.doi.org/10.1093/nar/gkr797] [PMID: 21948793]
[6]
Andersen, J.; Stuhr-Hansen, N.; Zachariassen, L.G.; Koldsø, H.; Schiøtt, B.; Strømgaard, K.; Kristensen, A.S. Molecular basis for selective serotonin reuptake inhibition by the antidepressant agent fluoxetine (Prozac). Mol. Pharmacol., 2014, 85(5), 703-714.
[http://dx.doi.org/10.1124/mol.113.091249] [PMID: 24516100]
[7]
Andersen, J.; Stuhr-Hansen, N.; Zachariassen, L.; Toubro, S.; Hansen, S.M.; Eildal, J.N.; Bond, A.D.; Bøgesø, K.P.; Bang-Andersen, B.; Kristensen, A.S.; Strømgaard, K. Molecular determinants for selective recognition of antidepressants in the human serotonin and norepinephrine transporters. Proc. Natl. Acad. Sci. USA, 2011, 108(29), 12137-12142.
[http://dx.doi.org/10.1073/pnas.1103060108] [PMID: 21730142]
[8]
Grouleff, J.; Ladefoged, L.K.; Koldsø, H.; Schiøtt, B. Monoamine transporters: insights from molecular dynamics simulations. Front. Pharmacol., 2015, 6, 235.
[http://dx.doi.org/10.3389/fphar.2015.00235] [PMID: 26528185]
[9]
Huot, P.; Fox, S.H.; Brotchie, J.M. Monoamine reuptake inhibitors in Parkinson’s disease. Parkinsons Dis., 2015, 2015, 609428
[http://dx.doi.org/10.1155/2015/609428] [PMID: 25810948]
[10]
Fu, T.; Zheng, G.; Tu, G.; Yang, F.; Chen, Y.; Yao, X.; Li, X.; Xue, W.; Zhu, F. Exploring the binding mechanism of metabotropic glutamate receptor 5 negative allosteric modulators in clinical trials by molecular dynamics simulations. ACS Chem. Neurosci., 2018, 9(6), 1492-1502.
[http://dx.doi.org/10.1021/acschemneuro.8b00059] [PMID: 29522307]
[11]
Xu, J.; Wang, P.; Yang, H.; Zhou, J.; Li, Y.; Li, X.; Xue, W.; Yu, C.; Tian, Y.; Zhu, F. Comparison of fda approved kinase targets to clinical trial ones: insights from their system profiles and drug-target interaction networks. BioMed Res. Int., 2016, 2016, 2509385
[http://dx.doi.org/10.1155/2016/2509385] [PMID: 27547755]
[12]
Aggarwal, S.; Mortensen, O.V. Overview of monoamine transporters. Curr. Protoc. Pharmacol, 2017, 79, 12.16.11-12.16.17.
[http://dx.doi.org/10.1002/cpph.32] [PMID: 29261228]
[13]
Caron, M.G.; Gether, U. Structural biology: Antidepressants at work. Nature, 2016, 532(7599), 320-321.
[http://dx.doi.org/10.1038/nature17883] [PMID: 27049942]
[14]
Hopkins, C.R. ACS chemical neuroscience molecule spotlight on viibryd (Vilazodone). ACS Chem. Neurosci., 2011, 2(10), 554.
[http://dx.doi.org/10.1021/cn200084v] [PMID: 22860155]
[15]
de Bartolomeis, A.; Fagiolini, A.; Maina, G. [Vortioxetine in the treatment of major depression]. Riv. Psichiatr., 2016, 51(6), 215-230.
[http://dx.doi.org/10.1708/2596.26720] [PMID: 27996982]
[16]
Nemeroff, C.B.; Entsuah, R.; Benattia, I.; Demitrack, M.; Sloan, D.M.; Thase, M.E. Comprehensive analysis of remission (COMPARE) with venlafaxine versus SSRIs. Biol. Psychiatry, 2008, 63(4), 424-434.
[http://dx.doi.org/10.1016/j.biopsych.2007.06.027] [PMID: 17888885]
[17]
Papakostas, G.I. Initial treatment approaches for patients with major depressive disorder. J. Clin. Psychiatry, 2009, 70(6) e18
[http://dx.doi.org/10.4088/JCP.8001tx7c] [PMID: 19573474]
[18]
Artigas, F. Future directions for serotonin and antidepressants. ACS Chem. Neurosci., 2013, 4(1), 5-8.
[http://dx.doi.org/10.1021/cn3001125] [PMID: 23336036]
[19]
Shao, L.; Li, W.; Xie, Q.; Yin, H. Triple reuptake inhibitors: a patent review (2006 - 2012). Expert Opin. Ther. Pat., 2014, 24(2), 131-154.
[http://dx.doi.org/10.1517/13543776.2014.859676] [PMID: 24289044]
[20]
Yu, G.; Zhang, M.; Saha, M.L.; Mao, Z.; Chen, J.; Yao, Y.; Zhou, Z.; Liu, Y.; Gao, C.; Huang, F.; Chen, X.; Stang, P.J. Antitumor activity of a unique polymer that incorporates a fluorescent self-assembled metallacycle. J. Am. Chem. Soc., 2017, 139(44), 15940-15949.
[http://dx.doi.org/10.1021/jacs.7b09224] [PMID: 29019660]
[21]
Liu, L.J.; Wang, W.; Huang, S.Y.; Hong, Y.; Li, G.; Lin, S.; Tian, J.; Cai, Z.; Wang, H.D.; Ma, D.L.; Leung, C.H. Inhibition of the Ras/Raf interaction and repression of renal cancer xenografts in vivo by an enantiomeric iridium(iii) metal-based compound. Chem. Sci. (Camb.), 2017, 8(7), 4756-4763.
[http://dx.doi.org/10.1039/C7SC00311K] [PMID: 28959398]
[22]
Yang, G.J.; Wang, W.; Mok, S.W.F.; Wu, C.; Law, B.Y.K.; Miao, X.M.; Wu, K.J.; Zhong, H.J.; Wong, C.Y.; Wong, V.K.W.; Ma, D.L.; Leung, C.H. Selective inhibition of lysine-specific demethylase 5a (kdm5a) using a rhodium(iii) complex for triple-negative breast cancer therapy. Angew. Chem. Int. Ed. Engl., 2018, 57(40), 13091-13095.
[http://dx.doi.org/10.1002/anie.201807305] [PMID: 29968419]
[23]
Fu, J.; Tang, J.; Wang, Y.; Cui, X.; Yang, Q.; Hong, J.; Li, X.; Li, S.; Chen, Y.; Xue, W.; Zhu, F. Discovery of the consistently well-performed analysis chain for SWATH-MS Based pharmacoproteomic quantification. Front. Pharmacol., 2018, 9, 681.
[http://dx.doi.org/10.3389/fphar.2018.00681] [PMID: 29997509]
[24]
Han, Z.J.; Xue, W.W.; Tao, L.; Zhu, F. Identification of novel immune-relevant drug target genes for Alzheimer’s Disease by combining ontology inference with network analysis. CNS Neurosci. Ther., 2018, 24(12), 1253-1263.
[http://dx.doi.org/10.1111/cns.13051] [PMID: 30106219]
[25]
Piscitelli, C.L.; Krishnamurthy, H.; Gouaux, E. Neurotransmitter/sodium symporter orthologue LeuT has a single high-affinity substrate site. Nature, 2010, 468(7327), 1129-1132.
[http://dx.doi.org/10.1038/nature09581] [PMID: 21179170]
[26]
Wang, H.; Goehring, A.; Wang, K.H.; Penmatsa, A.; Ressler, R.; Gouaux, E. Structural basis for action by diverse antidepressants on biogenic amine transporters. Nature, 2013, 503(7474), 141-145.
[http://dx.doi.org/10.1038/nature12648] [PMID: 24121440]
[27]
Penmatsa, A.; Wang, K.H.; Gouaux, E. X-ray structure of dopamine transporter elucidates antidepressant mechanism. Nature, 2013, 503(7474), 85-90.
[http://dx.doi.org/10.1038/nature12533] [PMID: 24037379]
[28]
Penmatsa, A.; Wang, K.H.; Gouaux, E. X-ray structures of Drosophila dopamine transporter in complex with nisoxetine and reboxetine. Nat. Struct. Mol. Biol., 2015, 22(6), 506-508.
[http://dx.doi.org/10.1038/nsmb.3029] [PMID: 25961798]
[29]
Wang, K.H.; Penmatsa, A.; Gouaux, E. Neurotransmitter and psychostimulant recognition by the dopamine transporter. Nature, 2015, 521(7552), 322-327.
[http://dx.doi.org/10.1038/nature14431] [PMID: 25970245]
[30]
Yu, C.Y.; Li, X.X.; Yang, H.; Li, Y.H.; Xue, W.W.; Chen, Y.Z.; Tao, L.; Zhu, F. Assessing the performances of protein function prediction algorithms from the perspectives of identification accuracy and false discovery rate. Int. J. Mol. Sci., 2018, 19(1) E183
[http://dx.doi.org/10.3390/ijms19010183] [PMID: 29316706]
[31]
Pratuangdejkul, J.; Schneider, B.; Launay, J.M.; Kellermann, O.; Manivet, P. Computational approaches for the study of serotonin and its membrane transporter SERT: implications for drug design in neurological sciences. Curr. Med. Chem., 2008, 15(30), 3214-3227.
[http://dx.doi.org/10.2174/092986708786848523] [PMID: 19075665]
[32]
Koldsø, H.; Grouleff, J.; Schiøtt, B. Insights to ligand binding to the monoamine transporters-from homology modeling to LeuBAT and dDAT. Front. Pharmacol., 2015, 6, 208.
[http://dx.doi.org/10.3389/fphar.2015.00208] [PMID: 26441663]
[33]
Celik, L.; Sinning, S.; Severinsen, K.; Hansen, C.G.; Møller, M.S.; Bols, M.; Wiborg, O.; Schiøtt, B. Binding of serotonin to the human serotonin transporter. Molecular modeling and experimental validation. J. Am. Chem. Soc., 2008, 130(12), 3853-3865.
[http://dx.doi.org/10.1021/ja076403h] [PMID: 18314975]
[34]
Koldsø, H.; Christiansen, A.B.; Sinning, S.; Schiøtt, B. Comparative modeling of the human monoamine transporters: similarities in substrate binding. ACS Chem. Neurosci., 2013, 4(2), 295-309.
[http://dx.doi.org/10.1021/cn300148r] [PMID: 23421681]
[35]
Combs, S.; Kaufmann, K.; Field, J.R.; Blakely, R.D.; Meiler, J. Y95 and E444 interaction required for high-affinity S-citalopram binding in the human serotonin transporter. ACS Chem. Neurosci., 2011, 2(2), 75-81.
[http://dx.doi.org/10.1021/cn100066p] [PMID: 22778858]
[36]
Severinsen, K.; Kraft, J.F.; Koldsø, H.; Vinberg, K.A.; Rothman, R.B.; Partilla, J.S.; Wiborg, O.; Blough, B.; Schiøtt, B.; Sinning, S. Binding of the amphetamine-like 1-phenyl-piperazine to monoamine transporters. ACS Chem. Neurosci., 2012, 3(9), 693-705.
[http://dx.doi.org/10.1021/cn300040f] [PMID: 23019496]
[37]
Xue, W.; Wang, P.; Li, B.; Li, Y.; Xu, X.; Yang, F.; Yao, X.; Chen, Y.Z.; Xu, F.; Zhu, F. Identification of the inhibitory mechanism of FDA approved selective serotonin reuptake inhibitors: an insight from molecular dynamics simulation study. Phys. Chem. Chem. Phys., 2016, 18(4), 3260-3271.
[http://dx.doi.org/10.1039/C5CP05771J] [PMID: 26745505]
[38]
Xue, W.; Yang, F.; Wang, P.; Zheng, G.; Chen, Y.; Yao, X.; Zhu, F. What contributes to serotonin-norepinephrine reuptake inhibitors’ dual-targeting mechanism? the key role of transmembrane domain 6 in human serotonin and norepinephrine transporters revealed by molecular dynamics simulation. ACS Chem. Neurosci., 2018, 9(5), 1128-1140.
[http://dx.doi.org/10.1021/acschemneuro.7b00490] [PMID: 29300091]
[39]
Yang, F.; Zheng, G.; Fu, T.; Li, X.; Tu, G.; Li, Y.H.; Yao, X.; Xue, W.; Zhu, F. Prediction of the binding mode and resistance profile for a dual-target pyrrolyl diketo acid scaffold against HIV-1 integrase and reverse-transcriptase-associated ribonuclease H. Phys. Chem. Chem. Phys., 2018, 20(37), 23873-23884.
[http://dx.doi.org/10.1039/C8CP01843J] [PMID: 29947629]
[40]
Severinsen, K.; Koldsø, H.; Thorup, K.A.; Schjøth-Eskesen, C.; Møller, P.T.; Wiborg, O.; Jensen, H.H.; Sinning, S.; Schiøtt, B. Binding of mazindol and analogs to the human serotonin and dopamine transporters. Mol. Pharmacol., 2014, 85(2), 208-217.
[http://dx.doi.org/10.1124/mol.113.088922] [PMID: 24214825]
[41]
Yang, C.; Wang, W.; Chen, L.; Liang, J.; Lin, S.; Lee, M.Y.; Ma, D.L.; Leung, C.H. Discovery of a VHL and HIF1α interaction inhibitor with in vivo angiogenic activity via structure-based virtual screening. Chem. Commun. (Camb.), 2016, 52(87), 12837-12840.
[http://dx.doi.org/10.1039/C6CC04938A] [PMID: 27709157]
[42]
Davey, G.E.; Adhireksan, Z.; Ma, Z.; Riedel, T.; Sharma, D.; Padavattan, S.; Rhodes, D.; Ludwig, A.; Sandin, S.; Murray, B.S.; Dyson, P.J.; Davey, C.A. Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation. Nat. Commun., 2017, 8(1), 1575.
[http://dx.doi.org/10.1038/s41467-017-01680-4] [PMID: 29146919]
[43]
Manepalli, S.; Geffert, L.M.; Surratt, C.K.; Madura, J.D. Discovery of novel selective serotonin reuptake inhibitors through development of a protein-based pharmacophore. J. Chem. Inf. Model., 2011, 51(9), 2417-2426.
[http://dx.doi.org/10.1021/ci200280m] [PMID: 21834587]
[44]
Schlessinger, A.; Geier, E.; Fan, H.; Irwin, J.J.; Shoichet, B.K.; Giacomini, K.M.; Sali, A. Structure-based discovery of prescription drugs that interact with the norepinephrine transporter, NET. Proc. Natl. Acad. Sci. USA, 2011, 108(38), 15810-15815.
[http://dx.doi.org/10.1073/pnas.1106030108] [PMID: 21885739]
[45]
Nolan, T.L.; Lapinsky, D.J.; Talbot, J.N.; Indarte, M.; Liu, Y.; Manepalli, S.; Geffert, L.M.; Amos, M.E.; Taylor, P.N.; Madura, J.D.; Surratt, C.K. Identification of a novel selective serotonin reuptake inhibitor by coupling monoamine transporter-based virtual screening and rational molecular hybridization. ACS Chem. Neurosci., 2011, 2(9), 544-552.
[http://dx.doi.org/10.1021/cn200044x] [PMID: 21966587]
[46]
Nolan, T.L.; Geffert, L.M.; Kolber, B.J.; Madura, J.D.; Surratt, C.K. Discovery of novel-scaffold monoamine transporter ligands via in silico screening with the S1 pocket of the serotonin transporter. ACS Chem. Neurosci., 2014, 5(9), 784-792.
[http://dx.doi.org/10.1021/cn500133b] [PMID: 25003748]
[47]
Yang, C.; Wang, W.; Liang, J.X.; Li, G.; Vellaisamy, K.; Wong, C.Y.; Ma, D.L.; Leung, C.H.A. A rhodium(iii)-based inhibitor of lysine-specific histone demethylase 1 as an epigenetic modulator in prostate cancer cells. J. Med. Chem., 2017, 60(6), 2597-2603.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00133] [PMID: 28219005]
[48]
Coleman, J.A.; Green, E.M.; Gouaux, E. X-ray structures and mechanism of the human serotonin transporter. Nature, 2016, 532(7599), 334-339.
[http://dx.doi.org/10.1038/nature17629] [PMID: 27049939]
[49]
Coleman, J.A.; Gouaux, E. Structural basis for recognition of diverse antidepressants by the human serotonin transporter. Nat. Struct. Mol. Biol., 2018, 25(2), 170-175.
[http://dx.doi.org/10.1038/s41594-018-0026-8] [PMID: 29379174]
[50]
Zhong, H.; Haddjeri, N.; Sánchez, C. Escitalopram, an antidepressant with an allosteric effect at the serotonin transporter--a review of current understanding of its mechanism of action. Psychopharmacology (Berl.), 2012, 219(1), 1-13.
[http://dx.doi.org/10.1007/s00213-011-2463-5] [PMID: 21901317]
[51]
Tosh, D.K.; Janowsky, A.; Eshleman, A.J.; Warnick, E.; Gao, Z.G.; Chen, Z.; Gizewski, E.; Auchampach, J.A.; Salvemini, D.; Jacobson, K.A. Scaffold repurposing of nucleosides (adenosine receptor agonists): enhanced activity at the human dopamine and norepinephrine sodium symporters. J. Med. Chem., 2017, 60(7), 3109-3123.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00141] [PMID: 28319392]
[52]
Kortagere, S.; Fontana, A.C.; Rose, D.R.; Mortensen, O.V. Identification of an allosteric modulator of the serotonin transporter with novel mechanism of action. Neuropharmacology, 2013, 72, 282-290.
[http://dx.doi.org/10.1016/j.neuropharm.2013.04.026] [PMID: 23632081]
[53]
Andersen, J.; Kristensen, A.S.; Bang-Andersen, B.; Strømgaard, K. Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters. Chem. Commun. (Camb.), 2009, (25), 3677-3692.
[http://dx.doi.org/10.1039/b903035m] [PMID: 19557250]
[54]
Nyola, A.; Karpowich, N.K.; Zhen, J.; Marden, J.; Reith, M.E.; Wang, D.N. Substrate and drug binding sites in LeuT. Curr. Opin. Struct. Biol., 2010, 20(4), 415-422.
[http://dx.doi.org/10.1016/j.sbi.2010.05.007] [PMID: 20739005]
[55]
Immadisetty, K.; Madura, J.D. A review of monoamine transporter-ligand interactions. Curr Comput Aided Drug Des, 2013, 9(4), 556-568.
[http://dx.doi.org/10.2174/15734099113096660039] [PMID: 24138394]
[56]
Orsolini, L.; Tomasetti, C.; Valchera, A.; Iasevoli, F.; Buonaguro, E.F.; Fornaro, M.; Fiengo, A.L.C.; Martinotti, G.; Vellante, F.; Matarazzo, I.; Vecchiotti, R.; Perna, G.; Di Nicola, M.; Carano, A.; Di Bartolomeis, A.; De Giannantonio, M.; De Berardis, D. Current and future perspectives on the major depressive disorder: focus on the new multimodal antidepressant vortioxetine. CNS Neurol. Disord. Drug Targets, 2017, 16(1), 65-92.
[http://dx.doi.org/10.2174/1871527315666161025140111] [PMID: 27781949]
[57]
Sørensen, L.; Andersen, J.; Thomsen, M.; Hansen, S.M.; Zhao, X.; Sandelin, A.; Strømgaard, K.; Kristensen, A.S. Interaction of antidepressants with the serotonin and norepinephrine transporters: mutational studies of the S1 substrate binding pocket. J. Biol. Chem., 2012, 287(52), 43694-43707.
[http://dx.doi.org/10.1074/jbc.M112.342212] [PMID: 23086945]
[58]
Plenge, P.; Mellerup, E.T. Antidepressive drugs can change the affinity of [3H]imipramine and [3H]paroxetine binding to platelet and neuronal membranes. Eur. J. Pharmacol., 1985, 119(1-2), 1-8.
[http://dx.doi.org/10.1016/0014-2999(85)90314-0] [PMID: 2935414]
[59]
Janowsky, A.; Tosh, D.K.; Eshleman, A.J.; Jacobson, K.A. Rigid adenine nucleoside derivatives as novel modulators of the human sodium symporters for dopamine and norepinephrine. J. Pharmacol. Exp. Ther., 2016, 357(1), 24-35.
[http://dx.doi.org/10.1124/jpet.115.229666] [PMID: 26813929]
[60]
Navratna, V.; Tosh, D.K.; Jacobson, K.A.; Gouaux, E. Thermostabilization and purification of the human dopamine transporter (hDAT) in an inhibitor and allosteric ligand bound conformation. PLoS One, 2018, 13(7) e0200085
[http://dx.doi.org/10.1371/journal.pone.0200085] [PMID: 29965988]
[61]
Li, Y.H.; Xu, J.Y.; Tao, L.; Li, X.F.; Li, S.; Zeng, X.; Chen, S.Y.; Zhang, P.; Qin, C.; Zhang, C.; Chen, Z.; Zhu, F.; Chen, Y.Z. Svm-prot 2016: a web-server for machine learning prediction of protein functional families from sequence irrespective of similarity. PLoS One, 2016, 11(8) e0155290
[http://dx.doi.org/10.1371/journal.pone.0155290] [PMID: 27525735]
[62]
Orsolini, L.; Tomasetti, C.; Valchera, A.; Iasevoli, F.; Buonaguro, E.F.; Vellante, F.; Fornaro, M.; Fiengo, A.; Mazza, M.; Vecchiotti, R.; Perna, G.; de Bartolomeis, A.; Martinotti, G.; Di Giannantonio, M.; De Berardis, D. New advances in the treatment of generalized anxiety disorder: the multimodal antidepressant vortioxetine. Expert Rev. Neurother., 2016, 16(5), 483-495.
[http://dx.doi.org/10.1586/14737175.2016.1173545] [PMID: 27050932]
[63]
Li, Y.H.; Yu, C.Y.; Li, X.X.; Zhang, P.; Tang, J.; Yang, Q.; Fu, T.; Zhang, X.; Cui, X.; Tu, G.; Zhang, Y.; Li, S.; Yang, F.; Sun, Q.; Qin, C.; Zeng, X.; Chen, Z.; Chen, Y.Z.; Zhu, F. Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics. Nucleic Acids Res., 2018, 46(D1), D1121-D1127.
[http://dx.doi.org/10.1093/nar/gkx1076] [PMID: 29140520]
[64]
Wang, P.; Zhang, X.; Fu, T.; Li, S.; Li, B.; Xue, W.; Yao, X.; Chen, Y.; Zhu, F. Differentiating physicochemical properties between addictive and nonaddictive adhd drugs revealed by molecular dynamics simulation studies. ACS Chem. Neurosci., 2017, 8(6), 1416-1428.
[http://dx.doi.org/10.1021/acschemneuro.7b00173] [PMID: 28557437]
[65]
Jing, E.; Straw-Wilson, K. Sexual dysfunction in selective serotonin reuptake inhibitors (SSRIs) and potential solutions: A narrative literature review. Ment Health Clin, 2016, 6(4), 191-196.
[http://dx.doi.org/10.9740/mhc.2016.07.191] [PMID: 29955469]
[66]
Wilson, E.; Lader, M. A review of the management of antidepressant discontinuation symptoms. Ther. Adv. Psychopharmacol., 2015, 5(6), 357-368.
[http://dx.doi.org/10.1177/2045125315612334] [PMID: 26834969]
[67]
Gordon, M.; Melvin, G. Selective serotonin re-uptake inhibitors--a review of the side effects in adolescents. Aust. Fam. Physician, 2013, 42(9), 620-623.
[PMID: 24024221]
[68]
Kasi, P.M.; Mounzer, R.; Gleeson, G.H. Cardiovascular side effects of atomoxetine and its interactions with inhibitors of the cytochrome p450 system. Case Rep. Med., 2011, 2011 952584
[http://dx.doi.org/10.1155/2011/952584] [PMID: 21765848]
[69]
Zheng, G.; Xue, W.; Yang, F.; Zhang, Y.; Chen, Y.; Yao, X.; Zhu, F. Revealing vilazodone’s binding mechanism underlying its partial agonism to the 5-HT1A receptor in the treatment of major depressive disorder. Phys. Chem. Chem. Phys., 2017, 19(42), 28885-28896.
[http://dx.doi.org/10.1039/C7CP05688E] [PMID: 29057413]
[70]
Kaplan, C.; Zhang, Y. Assessing the comparative-effectiveness of antidepressants commonly prescribed for depression in the US Medicare population. J. Ment. Health Policy Econ., 2012, 15(4), 171-178.
[PMID: 23525835]
[71]
Miyawaki, D.; Goto, A.; Iwakura, Y.; Hirai, K.; Miki, Y.; Asada, N.; Terakawa, H.; Inoue, K. Preschool-onset obsessive-compulsive disorder with complete remission. Neuropsychiatr. Dis. Treat., 2018, 14, 1747-1753.
[http://dx.doi.org/10.2147/NDT.S169797] [PMID: 30013347]
[72]
Upadhyaya, H.P.; Desaiah, D.; Schuh, K.J.; Bymaster, F.P.; Kallman, M.J.; Clarke, D.O.; Durell, T.M.; Trzepacz, P.T.; Calligaro, D.O.; Nisenbaum, E.S.; Emmerson, P.J.; Schuh, L.M.; Bickel, W.K.; Allen, A.J. A review of the abuse potential assessment of atomoxetine: a nonstimulant medication for attention-deficit/hyperactivity disorder. Psychopharmacology (Berl.), 2013, 226(2), 189-200.
[http://dx.doi.org/10.1007/s00213-013-2986-z] [PMID: 23397050]
[73]
Zheng, G.; Xue, W.; Wang, P.; Yang, F.; Li, B.; Li, X.; Li, Y.; Yao, X.; Zhu, F. Exploring the inhibitory mechanism of approved selective norepinephrine reuptake inhibitors and reboxetine enantiomers by molecular dynamics study. Sci. Rep., 2016, 6, 26883.
[http://dx.doi.org/10.1038/srep26883] [PMID: 27230580]
[74]
Thapar, A.; Cooper, M. Attention deficit hyperactivity disorder. Lancet, 2016, 387(10024), 1240-1250.
[http://dx.doi.org/10.1016/S0140-6736(15)00238-X] [PMID: 26386541]
[75]
Hannestad, J.; Gallezot, J.D.; Planeta-Wilson, B.; Lin, S.F.; Williams, W.A.; van Dyck, C.H.; Malison, R.T.; Carson, R.E.; Ding, Y.S. Clinically relevant doses of methylphenidate significantly occupy norepinephrine transporters in humans in vivo. Biol. Psychiatry, 2010, 68(9), 854-860.
[http://dx.doi.org/10.1016/j.biopsych.2010.06.017] [PMID: 20691429]
[76]
Benson, N.; Snelder, N.; Ploeger, B.; Napier, C.; Sale, H.; Birdsall, N.J.; Butt, R.P.; van der Graaf, P.H. Estimation of binding rate constants using a simultaneous mixed-effects method: application to monoamine transporter reuptake inhibitor reboxetine. Br. J. Pharmacol., 2010, 160(2), 389-398.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00719.x] [PMID: 20423348]
[77]
Yang, H.; Qin, C.; Li, Y.H.; Tao, L.; Zhou, J.; Yu, C.Y.; Xu, F.; Chen, Z.; Zhu, F.; Chen, Y.Z. Therapeutic target database update 2016: enriched resource for bench to clinical drug target and targeted pathway information. Nucleic Acids Res., 2016, 44(D1), D1069-D1074.
[http://dx.doi.org/10.1093/nar/gkv1230] [PMID: 26578601]
[78]
Volkow, N.D.; Fowler, J.S.; Wang, G.J.; Baler, R.; Telang, F. Imaging dopamine’s role in drug abuse and addiction. Neuropharmacology, 2009, 56(Suppl. 1), 3-8.
[http://dx.doi.org/10.1016/j.neuropharm.2008.05.022] [PMID: 18617195]
[79]
Lambert, O.; Bourin, M. SNRIs: mechanism of action and clinical features. Expert Rev. Neurother., 2002, 2(6), 849-858.
[http://dx.doi.org/10.1586/14737175.2.6.849] [PMID: 19810918]
[80]
Wang, P.; Fu, T.; Zhang, X.; Yang, F.; Zheng, G.; Xue, W.; Chen, Y.; Yao, X.; Zhu, F. Differentiating physicochemical properties between NDRIs and sNRIs clinically important for the treatment of ADHD. Biochim. Biophys. Acta, Gen. Subj., 2017, 1861(11 Pt A), 2766-2777.
[http://dx.doi.org/10.1016/j.bbagen.2017.07.022] [PMID: 28757337]
[81]
Maneeton, B.; Maneeton, N.; Likhitsathian, S.; Suttajit, S.; Narkpongphun, A.; Srisurapanont, M.; Woottiluk, P. Comparative efficacy, acceptability, and tolerability of lisdexamfetamine in child and adolescent ADHD: a meta-analysis of randomized, controlled trials. Drug Des. Devel. Ther., 2015, 9, 1927-1936.
[http://dx.doi.org/10.2147/DDDT.S79071] [PMID: 25897203]
[82]
Sharma, H.; Santra, S.; Dutta, A. Triple reuptake inhibitors as potential next-generation antidepressants: a new hope? Future Med. Chem., 2015, 7(17), 2385-2406.
[http://dx.doi.org/10.4155/fmc.15.134] [PMID: 26619226]
[83]
Subbaiah, M.A.M. Triple reuptake inhibitors as potential therapeutics for depression and other disorders: design paradigm and developmental challenges. J. Med. Chem., 2018, 61(6), 2133-2165.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01827] [PMID: 28731336]
[84]
Lane, R.M. Antidepressant drug development: Focus on triple monoamine reuptake inhibition. J. Psychopharmacol. (Oxford), 2015, 29(5), 526-544.
[http://dx.doi.org/10.1177/0269881114553252] [PMID: 25315829]
[85]
Liu, S.; Zha, C.; Nacro, K.; Hu, M.; Cui, W.; Yang, Y.L.; Bhatt, U.; Sambandam, A.; Isherwood, M.; Yet, L.; Herr, M.T.; Ebeltoft, S.; Hassler, C.; Fleming, L.; Pechulis, A.D.; Payen-Fornicola, A.; Holman, N.; Milanowski, D.; Cotterill, I.; Mozhaev, V.; Khmelnitsky, Y.; Guzzo, P.R.; Sargent, B.J.; Molino, B.F.; Olson, R.; King, D.; Lelas, S.; Li, Y.W.; Johnson, K.; Molski, T.; Orie, A.; Ng, A.; Haskell, R.; Clarke, W.; Bertekap, R.; O’Connell, J.; Lodge, N.; Sinz, M.; Adams, S.; Zaczek, R.; Macor, J.E. Design and synthesis of 4-heteroaryl 1,2,3,4-tetrahydroisoquinolines as triple reuptake inhibitors. ACS Med. Chem. Lett., 2014, 5(7), 760-765.
[http://dx.doi.org/10.1021/ml500053b] [PMID: 25050161]
[86]
Tao, L.; Zhu, F.; Xu, F.; Chen, Z.; Jiang, Y.Y.; Chen, Y.Z. Co-targeting cancer drug escape pathways confers clinical advantage for multi-target anticancer drugs. Pharmacol. Res., 2015, 102, 123-131.
[http://dx.doi.org/10.1016/j.phrs.2015.09.019] [PMID: 26438971]
[87]
Sanchez, C.; Asin, K.E.; Artigas, F. Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol. Ther., 2015, 145, 43-57.
[http://dx.doi.org/10.1016/j.pharmthera.2014.07.001] [PMID: 25016186]
[88]
Connolly, K.R.; Thase, M.E. Vortioxetine: a new treatment for major depressive disorder. Expert Opin. Pharmacother., 2016, 17(3), 421-431.
[http://dx.doi.org/10.1517/14656566.2016.1133588] [PMID: 26679430]
[89]
Tao, L.; Zhu, F.; Qin, C.; Zhang, C.; Xu, F.; Tan, C.Y.; Jiang, Y.Y.; Chen, Y.Z. Nature’s contribution to today’s pharmacopeia. Nat. Biotechnol., 2014, 32(10), 979-980.
[http://dx.doi.org/10.1038/nbt.3034] [PMID: 25299914]
[90]
Mnie-Filali, O.; El Mansari, M.; Scarna, H.; Zimmer, L.; Sánchez, C.; Haddjeri, N. [Escitalopram: a selective inhibitor and allosteric modulator of the serotonin transporter]. Encephale, 2007, 33(6), 965-972.
[http://dx.doi.org/10.1016/j.encep.2007.11.001] [PMID: 18789789]
[91]
Larsen, M.A.; Plenge, P.; Andersen, J.; Eildal, J.N.; Kristensen, A.S.; Bøgesø, K.P.; Gether, U.; Strømgaard, K.; Bang-Andersen, B.; Loland, C.J. Structure-activity relationship studies of citalopram derivatives: examining substituents conferring selectivity for the allosteric site in the 5-HT transporter. Br. J. Pharmacol., 2016, 173(5), 925-936.
[http://dx.doi.org/10.1111/bph.13411] [PMID: 26699847]
[92]
Iversen, L. Neurotransmitter transporters: fruitful targets for CNS drug discovery. Mol. Psychiatry, 2000, 5(4), 357-362.
[http://dx.doi.org/10.1038/sj.mp.4000728] [PMID: 10889545]
[93]
Mortensen, O.V.; Kortagere, S. Designing modulators of monoamine transporters using virtual screening techniques. Front. Pharmacol., 2015, 6, 223.
[http://dx.doi.org/10.3389/fphar.2015.00223] [PMID: 26483692]
[94]
Indarte, M.; Liu, Y.; Madura, J.D.; Surratt, C.K. Receptor-based discovery of a plasmalemmal monoamine transporter inhibitor via high throughput docking and pharmacophore modeling. ACS Chem. Neurosci., 2010, 1(3), 223-233.
[http://dx.doi.org/10.1021/cn900032u] [PMID: 20352074]
[95]
Erol, I.; Aksoydan, B.; Kantarcioglu, I.; Salmas, R.E.; Durdagi, S. Identification of novel serotonin reuptake inhibitors targeting central and allosteric binding sites: A virtual screening and molecular dynamics simulations study. J. Mol. Graph. Model., 2017, 74, 193-202.
[http://dx.doi.org/10.1016/j.jmgm.2017.02.001] [PMID: 28499269]
[96]
Topiol, S.; Bang-Andersen, B.; Sanchez, C.; Bøgesø, K.P. Exploration of insights, opportunities and caveats provided by the X-ray structures of hSERT. Bioorg. Med. Chem. Lett., 2016, 26(20), 5058-5064.
[http://dx.doi.org/10.1016/j.bmcl.2016.08.087] [PMID: 27624075]
[97]
Andersen, J.; Ladefoged, L.K.; Wang, D.; Kristensen, T.N.; Bang-Andersen, B.; Kristensen, A.S.; Schiøtt, B.; Strømgaard, K. Binding of the multimodal antidepressant drug vortioxetine to the human serotonin transporter. ACS Chem. Neurosci., 2015, 6(11), 1892-1900.
[http://dx.doi.org/10.1021/acschemneuro.5b00225] [PMID: 26389667]
[98]
Xue, W.; Wang, P.; Tu, G.; Yang, F.; Zheng, G.; Li, X.; Li, X.; Chen, Y.; Yao, X.; Zhu, F. Computational identification of the binding mechanism of a triple reuptake inhibitor amitifadine for the treatment of major depressive disorder. Phys. Chem. Chem. Phys., 2018, 20(9), 6606-6616.
[http://dx.doi.org/10.1039/C7CP07869B] [PMID: 29451287]
[99]
Zhu, F.; Li, X.X.; Yang, S.Y.; Chen, Y.Z. Clinical success of drug targets prospectively predicted by in silico study. Trends Pharmacol. Sci., 2018, 39(3), 229-231.
[http://dx.doi.org/10.1016/j.tips.2017.12.002] [PMID: 29295742]
[100]
Zhu, F.; Ma, X.H.; Qin, C.; Tao, L.; Liu, X.; Shi, Z.; Zhang, C.L.; Tan, C.Y.; Chen, Y.Z.; Jiang, Y.Y. Drug discovery prospect from untapped species: indications from approved natural product drugs. PLoS One, 2012, 7(7) e39782
[http://dx.doi.org/10.1371/journal.pone.0039782] [PMID: 22808057]
[101]
Zhu, F.; Qin, C.; Tao, L.; Liu, X.; Shi, Z.; Ma, X.; Jia, J.; Tan, Y.; Cui, C.; Lin, J.; Tan, C.; Jiang, Y.; Chen, Y. Clustered patterns of species origins of nature-derived drugs and clues for future bioprospecting. Proc. Natl. Acad. Sci. USA, 2011, 108(31), 12943-12948.
[http://dx.doi.org/10.1073/pnas.1107336108] [PMID: 21768386]
[102]
Wang, P.; Yang, F.; Yang, H.; Xu, X.; Liu, D.; Xue, W.; Zhu, F. Identification of dual active agents targeting 5-HT1A and SERT by combinatorial virtual screening methods. Biomed. Mater. Eng., 2015, 26(Suppl. 1), S2233-S2239.
[http://dx.doi.org/10.3233/BME-151529] [PMID: 26406003]
[103]
Yang, F.Y.; Fu, T.T.; Zhang, X.Y.; Hu, J.; Xue, W.W.; Zheng, G.X.; Li, B.; Li, Y.H.; Yao, X.J.; Zhu, F. Comparison of computational model and X-ray crystal structure of human serotonin transporter: potential application for the pharmacology of human monoamine transporters. Mol. Simul., 2017, 43(13-16), 1089-1098.
[http://dx.doi.org/10.1080/08927022.2017.1309653]
[104]
Seddik, A.; Geerke, D.P.; Stockner, T.; Holy, M.; Kudlacek, O.; Cozzi, N.V.; Ruoho, A.E.; Sitte, H.H.; Ecker, G.F. Combined simulation and mutation studies to elucidate selectivity of unsubstituted amphetamine-like cathinones at the dopamine transporter. Mol. Inform., 2017, 36(5-6)
[http://dx.doi.org/10.1002/minf.201600094] [PMID: 27860344]
[105]
Seddik, A.; Holy, M.; Weissensteiner, R.; Zdrazil, B.; Sitte, H.H.; Ecker, G.F. Probing the selectivity of monoamine transporter substrates by means of molecular modeling. Mol. Inform., 2013, 32(5-6), 409-413.
[http://dx.doi.org/10.1002/minf.201300013] [PMID: 23956802]
[106]
Koldsø, H.; Severinsen, K.; Tran, T.T.; Celik, L.; Jensen, H.H.; Wiborg, O.; Schiøtt, B.; Sinning, S. The two enantiomers of citalopram bind to the human serotonin transporter in reversed orientations. J. Am. Chem. Soc., 2010, 132(4), 1311-1322.
[http://dx.doi.org/10.1021/ja906923j] [PMID: 20055463]
[107]
Bisagno, V.; González, B.; Urbano, F.J. Cognitive enhancers versus addictive psychostimulants: The good and bad side of dopamine on prefrontal cortical circuits. Pharmacol. Res., 2016, 109, 108-118.
[http://dx.doi.org/10.1016/j.phrs.2016.01.013] [PMID: 26826399]
[108]
Schmeichel, B.E.; Zemlan, F.P.; Berridge, C.W. A selective dopamine reuptake inhibitor improves prefrontal cortex-dependent cognitive function: potential relevance to attention deficit hyperactivity disorder. Neuropharmacology, 2013, 64, 321-328.
[http://dx.doi.org/10.1016/j.neuropharm.2012.07.005] [PMID: 22796428]
[109]
Heal, D.J.; Gosden, J.; Smith, S.L. Dopamine reuptake transporter (DAT) “inverse agonism”--a novel hypothesis to explain the enigmatic pharmacology of cocaine. Neuropharmacology, 2014, 87, 19-40.
[http://dx.doi.org/10.1016/j.neuropharm.2014.06.012] [PMID: 24953830]
[110]
Mavel, S.; Meheux, N.; Guilloteau, D.; Emond, P. Synthesis and in vitro evaluation of fluorinated diphenyloxide derivatives and sulfur analogs as serotonin transporter ligands. Bioorg. Med. Chem., 2010, 18(1), 236-241.
[http://dx.doi.org/10.1016/j.bmc.2009.10.062] [PMID: 19926484]
[111]
Gu, X.; Izenwasser, S.; Wade, D.; Housman, A.; Gulasey, G.; Rhoden, J.B.; Savoie, C.D.; Mobley, D.L.; Lomenzo, S.A.; Trudell, M.L. Synthesis and structure-activity studies of benzyl ester meperidine and normeperidine derivatives as selective serotonin transporter ligands. Bioorg. Med. Chem., 2010, 18(23), 8356-8364.
[http://dx.doi.org/10.1016/j.bmc.2010.09.060] [PMID: 20980153]
[112]
Nencetti, S.; Mazzoni, M.R.; Ortore, G.; Lapucci, A.; Giuntini, J.; Orlandini, E.; Banti, I.; Nuti, E.; Lucacchini, A.; Giannaccini, G.; Rossello, A. Synthesis, molecular docking and binding studies of selective serotonin transporter inhibitors. Eur. J. Med. Chem., 2011, 46(3), 825-834.
[http://dx.doi.org/10.1016/j.ejmech.2010.12.018] [PMID: 21272963]
[113]
Vu, A.T.; Cohn, S.T.; Zhang, P.; Kim, C.Y.; Mahaney, P.E.; Bray, J.A.; Johnston, G.H.; Koury, E.J.; Cosmi, S.A.; Deecher, D.C.; Smith, V.A.; Harrison, J.E.; Leventhal, L.; Whiteside, G.T.; Kennedy, J.D.; Trybulski, E.J. 1-(Indolin-1-yl)-1-phenyl-3-propan-2-olamines as potent and selective norepinephrine reuptake inhibitors. J. Med. Chem., 2010, 53(5), 2051-2062.
[http://dx.doi.org/10.1021/jm901559e] [PMID: 20131864]
[114]
O’Neill, D.J.; Adedoyin, A.; Alfinito, P.D.; Bray, J.A.; Cosmi, S.; Deecher, D.C.; Fensome, A.; Harrison, J.; Leventhal, L.; Mann, C.; McComas, C.C.; Sullivan, N.R.; Spangler, T.B.; Uveges, A.J.; Trybulski, E.J.; Whiteside, G.T.; Zhang, P. Discovery of novel selective norepinephrine reuptake inhibitors: 4-[3-aryl-2,2-dioxido-2,1,3-benzothiadiazol-1(3H)-yl]-1-(methylamino)butan-2-ols (WYE-103231). J. Med. Chem., 2010, 53(11), 4511-4521.
[http://dx.doi.org/10.1021/jm100053t] [PMID: 20462211]
[115]
Banister, S.D.; Moussa, I.A.; Jordan, M.J.; Coster, M.J.; Kassiou, M. Oxo-bridged isomers of aza-trishomocubane sigma (sigma) receptor ligands: Synthesis, in vitro binding, and molecular modeling. Bioorg. Med. Chem. Lett., 2010, 20(1), 145-148.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.019] [PMID: 19954972]
[116]
Kaushal, N.; Seminerio, M.J.; Robson, M.J.; McCurdy, C.R.; Matsumoto, R.R. Pharmacological evaluation of SN79, a sigma (σ) receptor ligand, against methamphetamine-induced neurotoxicity in vivo. Eur. Neuropsychopharmacol., 2013, 23(8), 960-971.
[http://dx.doi.org/10.1016/j.euroneuro.2012.08.005] [PMID: 22921523]
[117]
Banister, S.D.; Moussa, I.A.; Beinat, C.; Reynolds, A.J.; Schiavini, P.; Jorgensen, W.T.; Kassiou, M. Trishomocubane as a scaffold for the development of selective dopamine transporter (DAT) ligands. Bioorg. Med. Chem. Lett., 2011, 21(1), 38-41.
[http://dx.doi.org/10.1016/j.bmcl.2010.11.075] [PMID: 21146989]
[118]
Motel, W.C.; Healy, J.R.; Viard, E.; Pouw, B.; Martin, K.; Matsumoto, R.R.; Coop, A. Chlorophenylpiperazine analogues as high affinity dopamine transporter ligands. Bioorg. Med. Chem. Lett., 2013, 23(24), 6920-6922.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.038] [PMID: 24211020]
[119]
Negus, S.S.; Banks, M.L. Decoding the structure of abuse potential for new psychoactive substances: structure-activity relationships for abuse-related effects of 4-substituted methcathinone analogs. Curr. Top. Behav. Neurosci., 2017, 32, 119-131.
[http://dx.doi.org/10.1007/7854_2016_18] [PMID: 27696217]
[120]
Eshleman, A.J.; Wolfrum, K.M.; Reed, J.F.; Kim, S.O.; Swanson, T.; Johnson, R.A.; Janowsky, A. Structure-activity relationships of substituted cathinones, with transporter binding, uptake, and release. J. Pharmacol. Exp. Ther., 2017, 360(1), 33-47.
[http://dx.doi.org/10.1124/jpet.116.236349] [PMID: 27799294]
[121]
Glennon, R.A.; Dukat, M. Structure-activity relationships of synthetic cathinones. Curr. Top. Behav. Neurosci., 2017, 32, 19-47.
[http://dx.doi.org/10.1007/7854_2016_41] [PMID: 27830576]
[122]
Zhu, F.; Han, L.; Zheng, C.; Xie, B.; Tammi, M.T.; Yang, S.; Wei, Y.; Chen, Y. What are next generation innovative therapeutic targets? Clues from genetic, structural, physicochemical, and systems profiles of successful targets. J. Pharmacol. Exp. Ther., 2009, 330(1), 304-315.
[http://dx.doi.org/10.1124/jpet.108.149955] [PMID: 19357322]
[123]
Angus, D.; Bingham, M.; Buchanan, D.; Dunbar, N.; Gibson, L.; Goodwin, R.; Haunsø, A.; Houghton, A.; Huggett, M.; Morphy, R.; Napier, S.; Nimz, O.; Passmore, J.; Walker, G. The identification, and optimisation of hERG selectivity, of a mixed NET/SERT re-uptake inhibitor for the treatment of pain. Bioorg. Med. Chem. Lett., 2011, 21(1), 271-275.
[http://dx.doi.org/10.1016/j.bmcl.2010.11.021] [PMID: 21112782]
[124]
Tsuruda, P.R.; Yung, J.; Martin, W.J.; Chang, R.; Mai, N.; Smith, J.A. Influence of ligand binding kinetics on functional inhibition of human recombinant serotonin and norepinephrine transporters. J. Pharmacol. Toxicol. Methods, 2010, 61(2), 192-204.
[http://dx.doi.org/10.1016/j.vascn.2009.12.003] [PMID: 20036748]
[125]
Shen, F.; Tsuruda, P.R.; Smith, J.A.; Obedencio, G.P.; Martin, W.J. Relative contributions of norepinephrine and serotonin transporters to antinociceptive synergy between monoamine reuptake inhibitors and morphine in the rat formalin model. PLoS One, 2013, 8(9) e74891
[http://dx.doi.org/10.1371/journal.pone.0074891] [PMID: 24098676]
[126]
Li, B.; Tang, J.; Yang, Q.; Li, S.; Cui, X.; Li, Y.; Chen, Y.; Xue, W.; Li, X.; Zhu, F. NOREVA: normalization and evaluation of MS-based metabolomics data. Nucleic Acids Res., 2017, 45(W1), W162-W170.
[http://dx.doi.org/10.1093/nar/gkx449] [PMID: 28525573]
[127]
Li, B.; Tang, J.; Yang, Q.; Cui, X.; Li, S.; Chen, S.; Cao, Q.; Xue, W.; Chen, N.; Zhu, F. Performance evaluation and online realization of data-driven normalization methods used in lc/ms based untargeted metabolomics analysis. Sci. Rep., 2016, 6, 38881.
[http://dx.doi.org/10.1038/srep38881] [PMID: 27958387]
[128]
Zhu, F.; Han, L.Y.; Chen, X.; Lin, H.H.; Ong, S.; Xie, B.; Zhang, H.L.; Chen, Y.Z. Homology-free prediction of functional class of proteins and peptides by support vector machines. Curr. Protein Pept. Sci., 2008, 9(1), 70-95.
[http://dx.doi.org/10.2174/138920308783565697] [PMID: 18336324]
[129]
Zhu, F.; Zheng, C.J.; Han, L.Y.; Xie, B.; Jia, J.; Liu, X.; Tammi, M.T.; Yang, S.Y.; Wei, Y.Q.; Chen, Y.Z. Trends in the exploration of anticancer targets and strategies in enhancing the efficacy of drug targeting. Curr. Mol. Pharmacol., 2008, 1(3), 213-232.
[http://dx.doi.org/10.2174/1874467210801030213] [PMID: 20021435]
[130]
Rao, H.B.; Zhu, F.; Yang, G.B.; Li, Z.R.; Chen, Y.Z. Update of PROFEAT: a web server for computing structural and physicochemical features of proteins and peptides from amino acid sequence.Nucleic Acids Res., 2011, 39(Web Server issue), W385-W390.
[http://dx.doi.org/10.1093/nar/gkr284] [PMID: 29609959]
[131]
Li, Y.H.; Wang, P.P.; Li, X.X.; Yu, C.Y.; Yang, H.; Zhou, J.; Xue, W.W.; Tan, J.; Zhu, F. The human kinome targeted by fda approved multi-target drugs and combination products: a comparative study from the drug-target interaction network perspective. PLoS One, 2016, 11(11) e0165737
[http://dx.doi.org/10.1371/journal.pone.0165737] [PMID: 27828998]
[132]
Smith, J.A.; Bourdet, D.L.; Daniels, O.T.; Ding, Y.S.; Gallezot, J.D.; Henry, S.; Kim, K.H.; Kshirsagar, S.; Martin, W.J.; Obedencio, G.P.; Stangeland, E.; Tsuruda, P.R.; Williams, W.; Carson, R.E.; Patil, S.T. Preclinical to clinical translation of CNS transporter occupancy of TD-9855, a novel norepinephrine and serotonin reuptake inhibitor. Int. J. Neuropsychopharmacol., 2014, 18(2) pyu027
[http://dx.doi.org/10.1093/ijnp/pyu027] [PMID: 25522383]
[133]
Vanderzee, P.; Koger, H.S.; Gootjes, J.; Hespe, W. Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur. J. Med. Chem., 1980, 15(4), 363-370.
[134]
Hsin, L.W.; Chang, L.T.; Rothman, R.B.; Dersch, C.M.; Jacobson, A.E.; Rice, K.C. Design and synthesis of 2- and 3-substituted-3-phenylpropyl analogs of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine and 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine: role of amino, fluoro, hydroxyl, methoxyl, methyl, methylene, and oxo substituents on affinity for the dopamine and serotonin transporters. J. Med. Chem., 2008, 51(9), 2795-2806.
[http://dx.doi.org/10.1021/jm701270n] [PMID: 18393401]
[135]
Torun, L.; Madras, B.K.; Meltzer, P.C. Synthesis and structure-activity relationship studies of 3-biaryl-8-oxabicyclo[3.2.1]octane-2-carboxylic acid methyl esters. Bioorg. Med. Chem., 2012, 20(8), 2762-2772.
[http://dx.doi.org/10.1016/j.bmc.2012.01.053] [PMID: 22398259]
[136]
Micheli, F.; Cavanni, P.; Arban, R.; Benedetti, R.; Bertani, B.; Bettati, M.; Bettelini, L.; Bonanomi, G.; Braggio, S.; Checchia, A.; Davalli, S.; Di Fabio, R.; Fazzolari, E.; Fontana, S.; Marchioro, C.; Minick, D.; Negri, M.; Oliosi, B.; Read, K.D.; Sartori, I.; Tedesco, G.; Tarsi, L.; Terreni, S.; Visentini, F.; Zocchi, A.; Zonzini, L. 1-(Aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes and 6-(aryl)-6-[alkoxyalkyl]-3-azabicyclo[3.1.0]hexanes: a new series of potent and selective triple reuptake inhibitors. J. Med. Chem., 2010, 53(6), 2534-2551.
[http://dx.doi.org/10.1021/jm901818u] [PMID: 20170186]
[137]
Micheli, F.; Cavanni, P.; Andreotti, D.; Arban, R.; Benedetti, R.; Bertani, B.; Bettati, M.; Bettelini, L.; Bonanomi, G.; Braggio, S.; Carletti, R.; Checchia, A.; Corsi, M.; Fazzolari, E.; Fontana, S.; Marchioro, C.; Merlo-Pich, E.; Negri, M.; Oliosi, B.; Ratti, E.; Read, K.D.; Roscic, M.; Sartori, I.; Spada, S.; Tedesco, G.; Tarsi, L.; Terreni, S.; Visentini, F.; Zocchi, A.; Zonzini, L.; Di Fabio, R. 6-(3,4-dichlorophenyl)-1-[(methyloxy)methyl]-3-azabicyclo[4.1.0]heptane: a new potent and selective triple reuptake inhibitor. J. Med. Chem., 2010, 53(13), 4989-5001.
[http://dx.doi.org/10.1021/jm100481d] [PMID: 20527970]
[138]
Zhang, F.; Shao, J.; Tian, J.; Zhong, Y.; Ye, L.; Meng, X.; Liu, Q.; Wang, H. Antidepressant-like effects of lpm580153, a novel potent triple reuptake inhibitor. Sci. Rep., 2016, 6, 24233.
[http://dx.doi.org/10.1038/srep24233] [PMID: 27052887]
[139]
Paudel, S.; Acharya, S.; Yoon, G.; Kim, K.M.; Cheon, S.H. Design, synthesis and in vitro activity of 1,4-disubstituted piperazines and piperidines as triple reuptake inhibitors. Bioorg. Med. Chem., 2017, 25(7), 2266-2276.
[http://dx.doi.org/10.1016/j.bmc.2017.02.051] [PMID: 28274674]
[140]
Paudel, S.; Min, X.; Acharya, S.; Khadka, D.B.; Yoon, G.; Kim, K.M.; Cheon, S.H. Triple reuptake inhibitors: Design, synthesis and structure-activity relationship of benzylpiperidine-tetrazoles. Bioorg. Med. Chem., 2017, 25(20), 5278-5289.
[http://dx.doi.org/10.1016/j.bmc.2017.07.046] [PMID: 28807575]
[141]
Zhu, X.Y.; Etukala, J.R.; Eyunni, S.V.; Setola, V.; Roth, B.L.; Ablordeppey, S.Y. Benzothiazoles as probes for the 5HT1A receptor and the serotonin transporter (SERT): a search for new dual-acting agents as potential antidepressants. Eur. J. Med. Chem., 2012, 53, 124-132.
[http://dx.doi.org/10.1016/j.ejmech.2012.03.042] [PMID: 22520153]
[142]
Czopek, A.; Kołaczkowski, M.; Bucki, A.; Byrtus, H.; Pawłowski, M.; Siwek, A.; Bojarski, A.J.; Bednarski, M.; Wróbel, D.; Wesołowska, A. Novel mannich bases, 5-arylimidazolidine-2,4-dione derivatives with dual 5-HT(1A) receptor and serotonin transporter affinity. Arch. Pharm. (Weinheim), 2013, 346(2), 98-109.
[http://dx.doi.org/10.1002/ardp.201200378] [PMID: 23288448]
[143]
Brinkø, A.; Larsen, M.T.; Koldsø, H.; Besenbacher, L.; Kolind, A.; Schiøtt, B.; Sinning, S.; Jensen, H.H. Synthesis and inhibitory evaluation of 3-linked imipramines for the exploration of the S2 site of the human serotonin transporter. Bioorg. Med. Chem., 2016, 24(12), 2725-2738.
[http://dx.doi.org/10.1016/j.bmc.2016.04.039] [PMID: 27160055]
[144]
Topiol, S.; Bang-Andersen, B.; Sanchez, C.; Plenge, P.; Loland, C.J.; Juhl, K.; Larsen, K.; Bregnedal, P.; Bøgesø, K.P. X-ray structure based evaluation of analogs of citalopram: Compounds with increased affinity and selectivity compared with R-citalopram for the allosteric site (S2) on hSERT. Bioorg. Med. Chem. Lett., 2017, 27(3), 470-478.
[http://dx.doi.org/10.1016/j.bmcl.2016.12.037] [PMID: 28041833]
[145]
Kumar, V.; Rahbek-Clemmensen, T.; Billesbølle, C.B.; Jorgensen, T.N.; Gether, U.; Newman, A.H. Novel and high affinity fluorescent ligands for the serotonin transporter based on (s)-citalopram. ACS Med. Chem. Lett., 2014, 5(6), 696-699.
[http://dx.doi.org/10.1021/ml5000806] [PMID: 24944746]
[146]
Tomlinson, I.D.; Iwamoto, H.; Blakely, R.D.; Rosenthal, S.J. Biotin tethered homotryptamine derivatives: high affinity probes of the human serotonin transporter (hSERT). Bioorg. Med. Chem. Lett., 2011, 21(6), 1678-1682.
[http://dx.doi.org/10.1016/j.bmcl.2011.01.102] [PMID: 21334895]
[147]
Liu, J.; Zhu, L.; Plössl, K.; Lieberman, B.P.; Kung, H.F. Synthesis and evaluation of novel N-fluoropyridyl derivatives of tropane as potential PET imaging agents for the dopamine transporter. Bioorg. Med. Chem. Lett., 2011, 21(10), 2962-2965.
[http://dx.doi.org/10.1016/j.bmcl.2011.03.051] [PMID: 21458259]
[148]
Zhou, Z.L.; Liu, H.L.; Wu, J.W.; Tsao, C.W.; Chen, W.H.; Liu, K.T.; Ho, Y. Combining structure-based pharmacophore and in silico approaches to discover novel selective serotonin reuptake inhibitors. Chem. Biol. Drug Des., 2013, 82(6), 705-717.
[http://dx.doi.org/10.1111/cbdd.12192] [PMID: 23865625]
[149]
Freyberg, Z.; Sonders, M.S.; Aguilar, J.I.; Hiranita, T.; Karam, C.S.; Flores, J.; Pizzo, A.B.; Zhang, Y.; Farino, Z.J.; Chen, A.; Martin, C.A.; Kopajtic, T.A.; Fei, H.; Hu, G.; Lin, Y.Y.; Mosharov, E.V.; McCabe, B.D.; Freyberg, R.; Wimalasena, K.; Hsin, L.W.; Sames, D.; Krantz, D.E.; Katz, J.L.; Sulzer, D.; Javitch, J.A. Mechanisms of amphetamine action illuminated through optical monitoring of dopamine synaptic vesicles in Drosophila brain. Nat. Commun., 2016, 7, 10652.
[http://dx.doi.org/10.1038/ncomms10652] [PMID: 26879809]
[150]
Comley, R.A.; Salinas, C.A.; Slifstein, M.; Petrone, M.; Marzano, C.; Bennacef, I.; Shotbolt, P.; Van der Aart, J.; Neve, M.; Iavarone, L.; Gomeni, R.; Laruelle, M.; Gray, F.A.; Gunn, R.N.; Rabiner, E.A. Monoamine transporter occupancy of a novel triple reuptake inhibitor in baboons and humans using positron emission tomography. J. Pharmacol. Exp. Ther., 2013, 346(2), 311-317.
[http://dx.doi.org/10.1124/jpet.112.202895] [PMID: 23685546]
[151]
Owens, M.J.; Knight, D.L.; Nemeroff, C.B. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol. Psychiatry, 2001, 50(5), 345-350.
[http://dx.doi.org/10.1016/S0006-3223(01)01145-3] [PMID: 11543737]
[152]
Uguz, F. Gastrointestinal side effects in the baby of a breastfeeding woman treated with low-dose fluvoxamine. J. Hum. Lact., 2015, 31(3), 371-373.
[http://dx.doi.org/10.1177/0890334415582207] [PMID: 25896469]
[153]
Tatsumi, M.; Groshan, K.; Blakely, R.D.; Richelson, E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur. J. Pharmacol., 1997, 340(2-3), 249-258.
[http://dx.doi.org/10.1016/S0014-2999(97)01393-9] [PMID: 9537821]
[154]
Owens, M.J.; Morgan, W.N.; Plott, S.J.; Nemeroff, C.B. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J. Pharmacol. Exp. Ther., 1997, 283(3), 1305-1322.
[PMID: 9400006]
[155]
Sanchez, C.; Reines, E.H.; Montgomery, S.A. A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike? Int. Clin. Psychopharmacol., 2014, 29(4), 185-196.
[http://dx.doi.org/10.1097/YIC.0000000000000023] [PMID: 24424469]
[156]
Edwards, J.G.; Glen-Bott, M. Does viloxazine have epileptogenic properties? J. Neurol. Neurosurg. Psychiatry, 1984, 47(9), 960-964.
[http://dx.doi.org/10.1136/jnnp.47.9.960] [PMID: 6434699]
[157]
Chebili, S.; Abaoub, A.; Mezouane, B.; Le Goff, J.F. [Antidepressants and sexual stimulation: the correlation]. Encephale, 1998, 24(3), 180-184.
[PMID: 9696909]
[158]
Grupper, C. [New iatrogenic acne: acne caused by amineptin (Survector)]. Ann. Dermatol. Venereol., 1988, 115(11), 1174-1176.
[PMID: 2977079]
[159]
Castot, A.; Benzaken, C.; Wagniart, F.; Efthymiou, M.L. [Amineptin abuse. Analysis of 155 cases. An evaluation of the official cooperative survey of the Regional Centers of Pharmacovigilance]. Therapie, 1990, 45(5), 399-405.
[PMID: 2260032]
[160]
Loland, C.J.; Mereu, M.; Okunola, O.M.; Cao, J.; Prisinzano, T.E.; Mazier, S.; Kopajtic, T.; Shi, L.; Katz, J.L.; Tanda, G.; Newman, A.H. R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol. Psychiatry, 2012, 72(5), 405-413.
[http://dx.doi.org/10.1016/j.biopsych.2012.03.022] [PMID: 22537794]
[161]
Battleday, R.M.; Brem, A.K. Modafinil for cognitive neuroenhancement in healthy non-sleep-deprived subjects: A systematic review. Eur. Neuropsychopharmacol., 2015, 25(11), 1865-1881.
[http://dx.doi.org/10.1016/j.euroneuro.2015.07.028] [PMID: 26381811]
[162]
Deecher, D.C.; Beyer, C.E.; Johnston, G.; Bray, J.; Shah, S.; Abou-Gharbia, M.; Andree, T.H. Desvenlafaxine succinate: A new serotonin and norepinephrine reuptake inhibitor. J. Pharmacol. Exp. Ther., 2006, 318(2), 657-665.
[http://dx.doi.org/10.1124/jpet.106.103382] [PMID: 16675639]
[163]
Bymaster, F.P.; Dreshfield-Ahmad, L.J.; Threlkeld, P.G.; Shaw, J.L.; Thompson, L.; Nelson, D.L.; Hemrick-Luecke, S.K.; Wong, D.T. Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology, 2001, 25(6), 871-880.
[http://dx.doi.org/10.1016/S0893-133X(01)00298-6] [PMID: 11750180]
[164]
Wong, M.C.; Chung, J.W.; Wong, T.K. Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ, 2007, 335(7610), 87.
[http://dx.doi.org/10.1136/bmj.39213.565972.AE] [PMID: 17562735]
[165]
Citrome, L. Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant--what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int. J. Clin. Pract., 2013, 67(11), 1089-1104.
[http://dx.doi.org/10.1111/ijcp.12298] [PMID: 24016209]
[166]
Sabatucci, J.P.; Mahaney, P.E.; Leiter, J.; Johnston, G.; Burroughs, K.; Cosmi, S.; Zhang, Y.; Ho, D.; Deecher, D.C.; Trybulski, E. Heterocyclic cycloalkanol ethylamines as norepinephrine reuptake inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(9), 2809-2812.
[http://dx.doi.org/10.1016/j.bmcl.2010.03.059] [PMID: 20378347]
[167]
Cipriani, A.; Furukawa, T.A.; Salanti, G.; Geddes, J.R.; Higgins, J.P.; Churchill, R.; Watanabe, N.; Nakagawa, A.; Omori, I.M.; McGuire, H.; Tansella, M.; Barbui, C. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet, 2009, 373(9665), 746-758.
[http://dx.doi.org/10.1016/S0140-6736(09)60046-5] [PMID: 19185342]
[168]
Simmler, L.D.; Buser, T.A.; Donzelli, M.; Schramm, Y.; Dieu, L.H.; Huwyler, J.; Chaboz, S.; Hoener, M.C.; Liechti, M.E. Pharmacological characterization of designer cathinones in vitro. Br. J. Pharmacol., 2013, 168(2), 458-470.
[http://dx.doi.org/10.1111/j.1476-5381.2012.02145.x] [PMID: 22897747]
[169]
Vitiello, B. Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function. Child Adolesc. Psychiatr. Clin. N. Am., 2008, 17(2), 459-474.
[http://dx.doi.org/10.1016/j.chc.2007.11.010] [PMID: 18295156]
[170]
Williard, R.L.; Middaugh, L.D.; Zhu, H.J.; Patrick, K.S. Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity. Behav. Pharmacol., 2007, 18(1), 39-51.
[http://dx.doi.org/10.1097/FBP.0b013e3280143226] [PMID: 17218796]
[171]
Cascade, E.; Kalali, A.H.; Wigal, S.B. Real-world data on: attention deficit hyperactivity disorder medication side effects. Psychiatry (Edgmont Pa.), 2010, 7(4), 13-15.
[PMID: 20508803]
[172]
Wynchank, D.; Bijlenga, D.; Beekman, A.T.; Kooij, J.J.S.; Penninx, B.W. Adult attention-deficit/hyperactivity disorder (ADHD) and insomnia: an update of the literature. Curr. Psychiatry Rep., 2017, 19(12), 98.
[http://dx.doi.org/10.1007/s11920-017-0860-0] [PMID: 29086065]
[173]
Markowitz, J.S.; Patrick, K.S. Differential pharmacokinetics and pharmacodynamics of methylphenidate enantiomers: does chirality matter? J. Clin. Psychopharmacol., 2008, 28(3)(Suppl. 2), S54-S61.
[http://dx.doi.org/10.1097/JCP.0b013e3181733560] [PMID: 18480678]
[174]
Markowitz, J.S.; DeVane, C.L.; Pestreich, L.K.; Patrick, K.S.; Muniz, R. A comprehensive in vitro screening of d-, l-, and dl-threo-methylphenidate: an exploratory study. J. Child Adolesc. Psychopharmacol., 2006, 16(6), 687-698.
[http://dx.doi.org/10.1089/cap.2006.16.687] [PMID: 17201613]
[175]
Hussain, F.; Frare, R.W.; Py Berrios, K.L. Drug abuse identification and pain management in dental patients: a case study and literature review. Gen. Dent., 2012, 60(4), 334-345.
[PMID: 22782046]
[176]
Fava, M.; Rush, A.J.; Thase, M.E.; Clayton, A.; Stahl, S.M.; Pradko, J.F.; Johnston, J.A. 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL. Prim. Care Companion J. Clin. Psychiatry, 2005, 7(3), 106-113.
[http://dx.doi.org/10.4088/PCC.v07n0305] [PMID: 16027765]
[177]
Skolnick, P.; Popik, P.; Janowsky, A.; Beer, B.; Lippa, A.S. Antidepressant-like actions of DOV 21,947: a “triple” reuptake inhibitor. Eur. J. Pharmacol., 2003, 461(2-3), 99-104.
[http://dx.doi.org/10.1016/S0014-2999(03)01310-4] [PMID: 12586204]
[178]
Zhang, R.; Li, X.; Shi, Y.; Shao, Y.; Sun, K.; Wang, A.; Sun, F.; Liu, W.; Wang, D.; Jin, J.; Li, Y. The effects of LPM570065, a novel triple reuptake inhibitor, on extracellular serotonin, dopamine and norepinephrine levels in rats. PLoS One, 2014, 9(3) e91775
[http://dx.doi.org/10.1371/journal.pone.0091775] [PMID: 24614602]
[179]
Skolnick, P.; Krieter, P.; Tizzano, J.; Basile, A.; Popik, P.; Czobor, P.; Lippa, A. Preclinical and clinical pharmacology of DOV 216,303, a “triple” reuptake inhibitor. CNS Drug Rev., 2006, 12(2), 123-134.
[http://dx.doi.org/10.1111/j.1527-3458.2006.00123.x] [PMID: 16958986]
[180]
Learned, S.; Graff, O.; Roychowdhury, S.; Moate, R.; Krishnan, K.R.; Archer, G.; Modell, J.G.; Alexander, R.; Zamuner, S.; Lavergne, A.; Evoniuk, G.; Ratti, E. Efficacy, safety, and tolerability of a triple reuptake inhibitor GSK372475 in the treatment of patients with major depressive disorder: two randomized, placebo- and active-controlled clinical trials. J. Psychopharmacol. (Oxford), 2012, 26(5), 653-662.
[http://dx.doi.org/10.1177/0269881111424931] [PMID: 22048884]
[181]
Koblan, K.S.; Hopkins, S.C.; Sarma, K.; Jin, F.; Goldman, R.; Kollins, S.H.; Loebel, A. Dasotraline for the treatment of attention-deficit/hyperactivity disorder: a randomized, double-blind, placebo-controlled, proof-of-concept trial in adults.neuropsychopharmacology, 2015, 40(12), 2745-2752.
[http://dx.doi.org/10.1038/npp.2015.124] [PMID: 25948101]
[182]
Heinrich, T.; Böttcher, H.; Gericke, R.; Bartoszyk, G.D.; Anzali, S.; Seyfried, C.A.; Greiner, H.E.; Van Amsterdam, C. Synthesis and structure--activity relationship in a class of indolebutylpiperazines as dual 5-HT(1A) receptor agonists and serotonin reuptake inhibitors. J. Med. Chem., 2004, 47(19), 4684-4692.
[http://dx.doi.org/10.1021/jm040793q] [PMID: 15341484]
[183]
Bang-Andersen, B.; Ruhland, T.; Jørgensen, M.; Smith, G.; Frederiksen, K.; Jensen, K.G.; Zhong, H.; Nielsen, S.M.; Hogg, S.; Mørk, A.; Stensbøl, T.B. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J. Med. Chem., 2011, 54(9), 3206-3221.
[http://dx.doi.org/10.1021/jm101459g] [PMID: 21486038]
[184]
Yamashita, A.; Singh, S.K.; Kawate, T.; Jin, Y.; Gouaux, E. Crystal structure of a bacterial homologue of Na+/Cl--dependent neurotransmitter transporters. Nature, 2005, 437(7056), 215-223.
[http://dx.doi.org/10.1038/nature03978] [PMID: 16041361]
[185]
Singh, S.K.; Yamashita, A.; Gouaux, E. Antidepressant binding site in a bacterial homologue of neurotransmitter transporters. Nature, 2007, 448(7156), 952-956.
[http://dx.doi.org/10.1038/nature06038] [PMID: 17687333]
[186]
Singh, S.K.; Piscitelli, C.L.; Yamashita, A.; Gouaux, E. A competitive inhibitor traps LeuT in an open-to-out conformation. Science, 2008, 322(5908), 1655-1661.
[http://dx.doi.org/10.1126/science.1166777] [PMID: 19074341]
[187]
Quick, M.; Winther, A.M.; Shi, L.; Nissen, P.; Weinstein, H.; Javitch, J.A. Binding of an octylglucoside detergent molecule in the second substrate (S2) site of LeuT establishes an inhibitor-bound conformation. Proc. Natl. Acad. Sci. USA, 2009, 106(14), 5563-5568.
[http://dx.doi.org/10.1073/pnas.0811322106] [PMID: 19307590]
[188]
Kroncke, B.M.; Horanyi, P.S.; Columbus, L. Structural origins of nitroxide side chain dynamics on membrane protein α-helical sites. Biochemistry, 2010, 49(47), 10045-10060.
[http://dx.doi.org/10.1021/bi101148w] [PMID: 20964375]
[189]
Piscitelli, C.L.; Gouaux, E. Insights into transport mechanism from LeuT engineered to transport tryptophan. EMBO J., 2012, 31(1), 228-235.
[http://dx.doi.org/10.1038/emboj.2011.353] [PMID: 21952050]
[190]
Krishnamurthy, H.; Gouaux, E. X-ray structures of LeuT in substrate-free outward-open and apo inward-open states. Nature, 2012, 481(7382), 469-474.
[http://dx.doi.org/10.1038/nature10737] [PMID: 22230955]
[191]
Wang, H.; Elferich, J.; Gouaux, E. Structures of LeuT in bicelles define conformation and substrate binding in a membrane-like context. Nat. Struct. Mol. Biol., 2012, 19(2), 212-219.
[http://dx.doi.org/10.1038/nsmb.2215] [PMID: 22245965]
[192]
Kantcheva, A.K.; Quick, M.; Shi, L.; Winther, A.M.; Stolzenberg, S.; Weinstein, H.; Javitch, J.A.; Nissen, P. Chloride binding site of neurotransmitter sodium symporters. Proc. Natl. Acad. Sci. USA, 2013, 110(21), 8489-8494.
[http://dx.doi.org/10.1073/pnas.1221279110] [PMID: 23641004]
[193]
Malinauskaite, L.; Said, S.; Sahin, C.; Grouleff, J.; Shahsavar, A.; Bjerregaard, H.; Noer, P.; Severinsen, K.; Boesen, T.; Schiøtt, B.; Sinning, S.; Nissen, P. A conserved leucine occupies the empty substrate site of LeuT in the Na(+)-free return state. Nat. Commun., 2016, 7, 11673.
[http://dx.doi.org/10.1038/ncomms11673] [PMID: 27221344]
[194]
Indarte, M.; Madura, J.D.; Surratt, C.K. Dopamine transporter comparative molecular modeling and binding site prediction using the LeuT(Aa) leucine transporter as a template. Proteins, 2008, 70(3), 1033-1046.
[http://dx.doi.org/10.1002/prot.21598] [PMID: 17847094]
[195]
Xhaard, H.; Backström, V.; Denessiouk, K.; Johnson, M.S. Coordination of Na(+) by monoamine ligands in dopamine, norepinephrine, and serotonin transporters. J. Chem. Inf. Model., 2008, 48(7), 1423-1437.
[http://dx.doi.org/10.1021/ci700255d] [PMID: 18543980]
[196]
Beuming, T.; Kniazeff, J.; Bergmann, M.L.; Shi, L.; Gracia, L.; Raniszewska, K.; Newman, A.H.; Javitch, J.A.; Weinstein, H.; Gether, U.; Loland, C.J. The binding sites for cocaine and dopamine in the dopamine transporter overlap. Nat. Neurosci., 2008, 11(7), 780-789.
[http://dx.doi.org/10.1038/nn.2146] [PMID: 18568020]
[197]
Kaufmann, K.W.; Dawson, E.S.; Henry, L.K.; Field, J.R.; Blakely, R.D.; Meiler, J. Structural determinants of species-selective substrate recognition in human and Drosophila serotonin transporters revealed through computational docking studies. Proteins, 2009, 74(3), 630-642.
[http://dx.doi.org/10.1002/prot.22178] [PMID: 18704946]
[198]
Guptaroy, B.; Zhang, M.; Bowton, E.; Binda, F.; Shi, L.; Weinstein, H.; Galli, A.; Javitch, J.A.; Neubig, R.R.; Gnegy, M.E. A juxtamembrane mutation in the N terminus of the dopamine transporter induces preference for an inward-facing conformation. Mol. Pharmacol., 2009, 75(3), 514-524.
[http://dx.doi.org/10.1124/mol.108.048744] [PMID: 19098122]
[199]
Andersen, J.; Taboureau, O.; Hansen, K.B.; Olsen, L.; Egebjerg, J.; Strømgaard, K.; Kristensen, A.S. Location of the antidepressant binding site in the serotonin transporter: importance of Ser-438 in recognition of citalopram and tricyclic antidepressants. J. Biol. Chem., 2009, 284(15), 10276-10284.
[http://dx.doi.org/10.1074/jbc.M806907200] [PMID: 19213730]
[200]
Ravna, A.W.; Sylte, I.; Dahl, S.G. Structure and localisation of drug binding sites on neurotransmitter transporters. J. Mol. Model., 2009, 15(10), 1155-1164.
[http://dx.doi.org/10.1007/s00894-009-0478-1] [PMID: 19238460]
[201]
Zhou, Z.; Zhen, J.; Karpowich, N.K.; Law, C.J.; Reith, M.E.; Wang, D.N. Antidepressant specificity of serotonin transporter suggested by three LeuT-SSRI structures. Nat. Struct. Mol. Biol., 2009, 16(6), 652-657.
[http://dx.doi.org/10.1038/nsmb.1602] [PMID: 19430461]
[202]
Tavoulari, S.; Forrest, L.R.; Rudnick, G. Fluoxetine (Prozac) binding to serotonin transporter is modulated by chloride and conformational changes. J. Neurosci., 2009, 29(30), 9635-9643.
[http://dx.doi.org/10.1523/JNEUROSCI.0440-09.2009] [PMID: 19641126]
[203]
Huang, X.; Gu, H.H.; Zhan, C.G. Mechanism for cocaine blocking the transport of dopamine: insights from molecular modeling and dynamics simulations. J. Phys. Chem. B, 2009, 113(45), 15057-15066.
[http://dx.doi.org/10.1021/jp900963n] [PMID: 19831380]
[204]
Andersen, J.; Olsen, L.; Hansen, K.B.; Taboureau, O.; Jørgensen, F.S.; Jørgensen, A.M.; Bang-Andersen, B.; Egebjerg, J.; Strømgaard, K.; Kristensen, A.S. Mutational mapping and modeling of the binding site for (S)-citalopram in the human serotonin transporter. J. Biol. Chem., 2010, 285(3), 2051-2063.
[http://dx.doi.org/10.1074/jbc.M109.072587] [PMID: 19892699]
[205]
Gedeon, P.C.; Indarte, M.; Surratt, C.K.; Madura, J.D. Molecular dynamics of leucine and dopamine transporter proteins in a model cell membrane lipid bilayer. Proteins, 2010, 78(4), 797-811.
[http://dx.doi.org/10.1002/prot.22601] [PMID: 19899168]
[206]
Sinning, S.; Musgaard, M.; Jensen, M.; Severinsen, K.; Celik, L.; Koldsø, H.; Meyer, T.; Bols, M.; Jensen, H.H.; Schiøtt, B.; Wiborg, O. Binding and orientation of tricyclic antidepressants within the central substrate site of the human serotonin transporter. J. Biol. Chem., 2010, 285(11), 8363-8374.
[http://dx.doi.org/10.1074/jbc.M109.045401] [PMID: 19948720]
[207]
Schmitt, K.C.; Mamidyala, S.; Biswas, S.; Dutta, A.K.; Reith, M.E. Bivalent phenethylamines as novel dopamine transporter inhibitors: evidence for multiple substrate-binding sites in a single transporter. J. Neurochem., 2010, 112(6), 1605-1618.
[http://dx.doi.org/10.1111/j.1471-4159.2010.06583.x] [PMID: 20067583]
[208]
Sucic, S.; Dallinger, S.; Zdrazil, B.; Weissensteiner, R.; Jørgensen, T.N.; Holy, M.; Kudlacek, O.; Seidel, S.; Cha, J.H.; Gether, U.; Newman, A.H.; Ecker, G.F.; Freissmuth, M.; Sitte, H.H. The N terminus of monoamine transporters is a lever required for the action of amphetamines. J. Biol. Chem., 2010, 285(14), 10924-10938.
[http://dx.doi.org/10.1074/jbc.M109.083154] [PMID: 20118234]
[209]
Field, J.R.; Henry, L.K.; Blakely, R.D. Transmembrane domain 6 of the human serotonin transporter contributes to an aqueously accessible binding pocket for serotonin and the psychostimulant 3,4-methylene dioxymethamphetamine. J. Biol. Chem., 2010, 285(15), 11270-11280.
[http://dx.doi.org/10.1074/jbc.M109.093658] [PMID: 20159976]
[210]
Torres-Altoro, M.I.; Kuntz, C.P.; Nichols, D.E.; Barker, E.L. Structural analysis of the extracellular entrance to the serotonin transporter permeation pathway. J. Biol. Chem., 2010, 285(20), 15369-15379.
[http://dx.doi.org/10.1074/jbc.M109.088138] [PMID: 20304925]
[211]
Wenthur, C.J.; Rodríguez, G.J.; Kuntz, C.P.; Barker, E.L. Conformational flexibility of transmembrane helix VII of the human serotonin transporter impacts ion dependence and transport. Biochem. Pharmacol., 2010, 80(9), 1418-1426.
[http://dx.doi.org/10.1016/j.bcp.2010.07.005] [PMID: 20637736]
[212]
Bisgaard, H.; Larsen, M.A.; Mazier, S.; Beuming, T.; Newman, A.H.; Weinstein, H.; Shi, L.; Loland, C.J.; Gether, U. The binding sites for benztropines and dopamine in the dopamine transporter overlap. Neuropharmacology, 2011, 60(1), 182-190.
[http://dx.doi.org/10.1016/j.neuropharm.2010.08.021] [PMID: 20816875]
[213]
Sarker, S.; Weissensteiner, R.; Steiner, I.; Sitte, H.H.; Ecker, G.F.; Freissmuth, M.; Sucic, S. The high-affinity binding site for tricyclic antidepressants resides in the outer vestibule of the serotonin transporter. Mol. Pharmacol., 2010, 78(6), 1026-1035.
[http://dx.doi.org/10.1124/mol.110.067538] [PMID: 20829432]
[214]
Tavoulari, S.; Rizwan, A.N.; Forrest, L.R.; Rudnick, G. Reconstructing a chloride-binding site in a bacterial neurotransmitter transporter homologue. J. Biol. Chem., 2011, 286(4), 2834-2842.
[http://dx.doi.org/10.1074/jbc.M110.186064] [PMID: 21115480]
[215]
Shan, J.; Javitch, J.A.; Shi, L.; Weinstein, H. The substrate-driven transition to an inward-facing conformation in the functional mechanism of the dopamine transporter. PLoS One, 2011, 6(1) e16350
[http://dx.doi.org/10.1371/journal.pone.0016350] [PMID: 21298009]
[216]
Hill, E.R.; Huang, X.; Zhan, C.G.; Ivy Carroll, F.; Gu, H.H. Interaction of tyrosine 151 in norepinephrine transporter with the 2β group of cocaine analog RTI-113. Neuropharmacology, 2011, 61(1-2), 112-120.
[http://dx.doi.org/10.1016/j.neuropharm.2011.03.014] [PMID: 21420984]
[217]
Gabrielsen, M.; Ravna, A.W.; Kristiansen, K.; Sylte, I. Substrate binding and translocation of the serotonin transporter studied by docking and molecular dynamics simulations. J. Mol. Model., 2012, 18(3), 1073-1085.
[http://dx.doi.org/10.1007/s00894-011-1133-1] [PMID: 21670993]
[218]
Koldsø, H.; Noer, P.; Grouleff, J.; Autzen, H.E.; Sinning, S.; Schiøtt, B. Unbiased simulations reveal the inwardfacing conformation of the human serotonin transporter and Na(+) ion release.PLOS Comput. Biol; , 2011, 7, . (10) e1002246
[http://dx.doi.org/10.1371/journal.pcbi.1002246] [PMID: 22046120]
[219]
Gabrielsen, M.; Kurczab, R.; Ravna, A.W.; Kufareva, I.; Abagyan, R.; Chilmonczyk, Z.; Bojarski, A.J.; Sylte, I. Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol. Eur. J. Med. Chem., 2012, 47(1), 24-37.
[http://dx.doi.org/10.1016/j.ejmech.2011.09.056] [PMID: 22071255]
[220]
Jarończyk, M.; Wołosewicz, K.; Gabrielsen, M.; Nowak, G.; Kufareva, I.; Mazurek, A.P.; Ravna, A.W.; Abagyan, R.; Bojarski, A.J.; Sylte, I.; Chilmonczyk, Z. Synthesis, in vitro binding studies and docking of long-chain arylpiperazine nitroquipazine analogues, as potential serotonin transporter inhibitors. Eur. J. Med. Chem., 2012, 49, 200-210.
[http://dx.doi.org/10.1016/j.ejmech.2012.01.012] [PMID: 22309909]
[221]
Wang, C.I.; Shaikh, N.H.; Ramu, S.; Lewis, R.J. A second extracellular site is required for norepinephrine transport by the human norepinephrine transporter. Mol. Pharmacol., 2012, 82(5), 898-909.
[http://dx.doi.org/10.1124/mol.112.080630] [PMID: 22874414]
[222]
Reith, M.E.; Ali, S.; Hashim, A.; Sheikh, I.S.; Theddu, N.; Gaddiraju, N.V.; Mehrotra, S.; Schmitt, K.C.; Murray, T.F.; Sershen, H.; Unterwald, E.M.; Davis, F.A. Novel C-1 substituted cocaine analogs unlike cocaine or benztropine. J. Pharmacol. Exp. Ther., 2012, 343(2), 413-425.
[http://dx.doi.org/10.1124/jpet.112.193771] [PMID: 22895898]
[223]
Plenge, P.; Shi, L.; Beuming, T.; Te, J.; Newman, A.H.; Weinstein, H.; Gether, U.; Loland, C.J. Steric hindrance mutagenesis in the conserved extracellular vestibule impedes allosteric binding of antidepressants to the serotonin transporter. J. Biol. Chem., 2012, 287(47), 39316-39326.
[http://dx.doi.org/10.1074/jbc.M112.371765] [PMID: 23007398]
[224]
Merchant, B.A.; Madura, J.D. Insights from molecular dynamics: the binding site of cocaine in the dopamine transporter and permeation pathways of substrates in the leucine and dopamine transporters. J. Mol. Graph. Model., 2012, 38, 1-12.
[http://dx.doi.org/10.1016/j.jmgm.2012.05.007] [PMID: 23079638]
[225]
Stockner, T.; Montgomery, T.R.; Kudlacek, O.; Weissensteiner, R.; Ecker, G.F.; Freissmuth, M.; Sitte, H.H. Mutational analysis of the high-affinity zinc binding site validates a refined human dopamine transporter homology model. PLOS Comput. Biol., 2013, 9(2) e1002909
[http://dx.doi.org/10.1371/journal.pcbi.1002909] [PMID: 23436987]
[226]
Koldsø, H.; Autzen, H.E.; Grouleff, J.; Schiøtt, B. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations. PLoS One, 2013, 8(6) e63635
[http://dx.doi.org/10.1371/journal.pone.0063635] [PMID: 23776432]
[227]
Beckman, M.L.; Pramod, A.B.; Perley, D.; Henry, L.K. Stereoselective inhibition of serotonin transporters by antimalarial compounds. Neurochem. Int., 2014, 73, 98-106.
[http://dx.doi.org/10.1016/j.neuint.2013.10.009] [PMID: 24161619]
[228]
Wilson, J.N.; Ladefoged, L.K.; Babinchak, W.M.; Schiøtt, B. Binding-induced fluorescence of serotonin transporter ligands: A spectroscopic and structural study of 4-(4-(dimethylamino)phenyl)-1-methylpyridinium (APP(+)) and APP(+) analogues. ACS Chem. Neurosci., 2014, 5(4), 296-304.
[http://dx.doi.org/10.1021/cn400230x] [PMID: 24460204]
[229]
Okunola-Bakare, O.M.; Cao, J.; Kopajtic, T.; Katz, J.L.; Loland, C.J.; Shi, L.; Newman, A.H. Elucidation of structural elements for selectivity across monoamine transporters: novel 2-[(diphenylmethyl)sulfinyl]acetamide (modafinil) analogues. J. Med. Chem., 2014, 57(3), 1000-1013.
[http://dx.doi.org/10.1021/jm401754x] [PMID: 24494745]
[230]
Gabrielsen, M.; Kurczab, R.; Siwek, A.; Wolak, M.; Ravna, A.W.; Kristiansen, K.; Kufareva, I.; Abagyan, R.; Nowak, G.; Chilmonczyk, Z.; Sylte, I.; Bojarski, A.J. Identification of novel serotonin transporter compounds by virtual screening. J. Chem. Inf. Model., 2014, 54(3), 933-943.
[http://dx.doi.org/10.1021/ci400742s] [PMID: 24521202]
[231]
Dahal, R.A.; Pramod, A.B.; Sharma, B.; Krout, D.; Foster, J.D.; Cha, J.H.; Cao, J.; Newman, A.H.; Lever, J.R.; Vaughan, R.A.; Henry, L.K. Computational and biochemical docking of the irreversible cocaine analog RTI 82 directly demonstrates ligand positioning in the dopamine transporter central substrate-binding site. J. Biol. Chem., 2014, 289(43), 29712-29727.
[http://dx.doi.org/10.1074/jbc.M114.571521] [PMID: 25179220]
[232]
Sakloth, F.; Kolanos, R.; Mosier, P.D.; Bonano, J.S.; Banks, M.L.; Partilla, J.S.; Baumann, M.H.; Negus, S.S.; Glennon, R.A. Steric parameters, molecular modeling and hydropathic interaction analysis of the pharmacology of para-substituted methcathinone analogues. Br. J. Pharmacol., 2015, 172(9), 2210-2218.
[http://dx.doi.org/10.1111/bph.13043] [PMID: 25522019]
[233]
Cheng, M.H.; Block, E.; Hu, F.; Cobanoglu, M.C.; Sorkin, A.; Bahar, I. Insights into the modulation of dopamine transporter function by amphetamine, orphenadrine, and cocaine binding. Front. Neurol., 2015, 6, 134.
[http://dx.doi.org/10.3389/fneur.2015.00134] [PMID: 26106364]
[234]
Cheng, M.H.; Bahar, I. Molecular mechanism of dopamine transport by human dopamine transporter. Structure, 2015, 23(11), 2171-2181.
[http://dx.doi.org/10.1016/j.str.2015.09.001] [PMID: 26481814]
[235]
Davis, B.A.; Nagarajan, A.; Forrest, L.R.; Singh, S.K. Mechanism of paroxetine (paxil) inhibition of the serotonin transporter. Sci. Rep., 2016, 6, 23789.
[http://dx.doi.org/10.1038/srep23789] [PMID: 27032980]
[236]
Andersen, J.; Ladefoged, L.K.; Kristensen, T.N.; Munro, L.; Grouleff, J.; Stuhr-Hansen, N.; Kristensen, A.S.; Schiøtt, B.; Strømgaard, K. Interrogating the molecular basis for substrate recognition in serotonin and dopamine transporters with high-affinity substrate-based bivalent ligands. ACS Chem. Neurosci., 2016, 7(10), 1406-1417.
[http://dx.doi.org/10.1021/acschemneuro.6b00164] [PMID: 27425420]
[237]
Talbot, J.N.; Geffert, L.M.; Jorvig, J.E.; Goldstein, R.I.; Nielsen, C.L.; Wolters, N.E.; Amos, M.E.; Munro, C.A.; Dallman, E.; Mereu, M.; Tanda, G.; Katz, J.L.; Indarte, M.; Madura, J.D.; Choi, H.; Leak, R.K.; Surratt, C.K. Rapid and sustained antidepressant properties of an NMDA antagonist/monoamine reuptake inhibitor identified via transporter-based virtual screening. Pharmacol. Biochem. Behav., 2016, 150-151, 22-30.
[http://dx.doi.org/10.1016/j.pbb.2016.08.007] [PMID: 27569602]
[238]
Haddad, Y.; Heger, Z.; Adam, V. Guidelines for homology modeling of dopamine, norepinephrine, and serotonin transporters. ACS Chem. Neurosci., 2016, 7(11), 1607-1613.
[http://dx.doi.org/10.1021/acschemneuro.6b00242] [PMID: 27596073]
[239]
Djikic, T.; Martí, Y.; Spyrakis, F.; Lau, T.; Benedetti, P.; Davey, G.; Schloss, P.; Yelekci, K. Human dopamine transporter: the first implementation of a combined in silico/in vitro approach revealing the substrate and inhibitor specificities. J. Biomol. Struct. Dyn., 2019, 37(2), 291-306.
[http://dx.doi.org/10.1080/07391102.2018.1426044] [PMID: 29334320]
[240]
Mena-Avila, E.; Márquez-Gómez, R.; Aquino-Miranda, G.; Nieto-Alamilla, G.; Arias-Montaño, J.A. Clobenpropit, a histamine H3 receptor antagonist/inverse agonist, inhibits [3H]-dopamine uptake by human neuroblastoma SH-SY5Y cells and rat brain synaptosomes. Pharmacol. Rep., 2018, 70(1), 146-155.
[http://dx.doi.org/10.1016/j.pharep.2017.08.007] [PMID: 29414147]
[241]
Macdougall, I.J.; Griffith, R. Pharmacophore design and database searching for selective monoamine neurotransmitter transporter ligands. J. Mol. Graph. Model., 2008, 26(7), 1113-1124.
[http://dx.doi.org/10.1016/j.jmgm.2007.10.003] [PMID: 18023378]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 27
ISSUE: 23
Year: 2020
Page: [3830 - 3876]
Pages: 47
DOI: 10.2174/0929867325666181009123218
Price: $65

Article Metrics

PDF: 42
HTML: 2