Abstract
Depression is nowadays a major contributor to global burden of disease. The most commonly prescribed drugs influence monoaminergic pathways, mainly concentrating on serotonin. Unfortunately, there are several drawbacks associated with these drugs, namely late onset of action, risk of suicide and adverse effects: mainly nausea, vomiting and sexual dysfunction. Therefore there is still need for new drugs with possibly high efficacy and fewer side effects.
In this paper selected compounds which inhibit serotonin reuptake by acting on the serotonin transporter (SERT) and various serotoninergic receptors are presented. We also discuss the ways in which their mechanism of action can be modified to improve pharmacological profile.
Here, we focus on describing drugs’ potency, efficacy and adverse effects. Additional applications, apart from depression, are also discussed.
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Elhwuegi AS. Central monoamines and their role in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:435–51.
Mathew SJ, Manji HK, Charney DS. Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology 2008;33:2080–92.
Ribeiro P, Patocka N. Neurotransmitter transporters in schistosomes: structure, function and prospects for drug discovery. Parasitol Int 2013;62:629–38.
Lau T, Schloss P. Differential regulation of serotonin transporter cell surface expression. Wiley Interdiscip Rev Membr Transp Signal 2012;1:259–68.
Ramamoorthy S, Shippenberg TS, Jayanthi LD. Regulation of monoamine transporters: role of transporter phosphorylation. Pharmacol Ther 2011;129:220–38.
Blakely RD, Bauman AL. Biogenic amine transporters: regulation in flux. Curr Opin Neurobiol 2000;10:328–36.
Abraham G, Milev R. Stuart lawson J: T3 augmentation of SSRI resistant depression. J Affect Disord 2006;91:211–5.
Brunton L, Chabner B, Knollman B. Goodman and Gilman’s the pharmacological basis of therapeutics. 12th ed. McGraw-Hill Education; 2011.
Katzung B, Trevor A. Basic & clinical pharmacology. 13th ed. McGraw-Hill Education; 2014.
Artigas F. Serotonin receptors involved in antidepressant effects. Pharmacol Ther 2013;137:119–31.
Romero L, Bel N, Artigas F, de Montigny C, Blier P. Effect of pindolol on the function of pre- and postsynaptic 5-HT1A receptors: in vivo microdialysis and electrophysiological studies in the rat brain. Neuropsychopharmacology 1996;15:349–60.
Artigas F, Celada P, Laruelle M, Adell A. How does pindolol improve antidepressant action? Trends Pharmacol Sci 2001;22:224–8.
Kimura S, Ohi Y, Haji A. Effects of cholinesterase inhibitors and serotonin-1A receptor agonists on morphine-induced ventilatory depression and antinociception in rats. Eur J Pharmacol 2013;703:33–41.
Svenningsson P, Chergui K, Rachleff I, Flajolet M, Zhang X, El Yacoubi M, et al. Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 2006;311:77–80.
López-Figueroa AL, Norton CS, López-Figueroa MO, Armellini-Dodel D, Burke S, Akil H, et al. Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Biol Psychiatry 2004;55:225–33.
Davidson C, Stamford JA. Effect of chronic paroxetine treatment on 5-HT1B and 5-HT1D autoreceptors in rat dorsal raphe nucleus. Neurochem Int 2000;36:91–6.
Cooke HJ, Sidhu M, Wang YZ. Activation of 5-HT1P receptors on submucosal afferents subsequently triggers VIP neurons and chloride secretion in the guinea-pig colon. J Auton Nerv Syst 1997;66:105–10.
Hamon M, Blier P. Monoamine neurocircuitry in depression and strategies for new treatments. Prog Neuropsychopharmacol Biol Psychiatry 2013;45:54–63.
Yang HY, Tae J, Seo YW, Kim YJ, Im HY, Choi GD, et al. Novel pyrimidoazepine analogs as serotonin 5-HT(2A) and 5-HT(2C) receptor ligands for the treatment of obesity. Eur J Med Chem 2013;63:558–69.
Mbaki Y, Gardiner J, McMurray G, Ramage AG. 5-HT 2A receptor activation of the external urethral sphincter and 5-HT 2C receptor inhibition of micturition: a study based on pharmacokinetics in the anaesthetized female rat. Eur J Pharmacol 2012;682:142–52.
Cavero I, Safety Guillon J-M. Pharmacology assessment of drugs with biased 5-HT(2B) receptor agonism mediating cardiac valvulopathy. J Pharmacol Toxicol Methods 2014;69:150–61.
Li X, Ma Y, Wu X, Hao Z, Yin J, Shen J, et al. Serotonin acts as a novel regulator of interleukin-6 secretion in osteocytes through the activation of the 5-HT2B receptor and the ERK1/2 signalling pathway. Biochem Biophys Res Commun 2013;441:809–14.
Cervantes-Durán C, Rocha-González HI, Granados-Soto V. Peripheral and spinal 5-HT receptors participate in the pronociceptive and antinociceptive effects of fluoxetine in rats. Neuroscience 2013;252:396–409.
Bharti S, Singh R, Chauhan SS, Hussain T, Al-Attas OS, Arya DS. Phosphorylation of Akt/GSK-3b/eNOS amplifies 5-HT 2 B receptor blockade mediated anti-hypertrophic effect in rats. FEBS Lett 2012;586:180–5.
Hutcheson JD, Ryzhova LM, Setola V, Merryman WD. 5-HT2B antagonism arrests non-canonical TGF-b1-induced valvular myofibroblast differentiation. J Mol Cell Cardiol 2012;53:707–14.
Moss N, Choi Y, Cogan D, Flegg A, Kahrs A, Loke P, et al. A new class of 5-HT2B antagonists possesses favorable potency, selectivity, and rat pharmacokinetic properties. Bioorg Med Chem Lett 2009;19:2206–10.
Löfdahl A, Rydell-Törmänen K, Müller C, Martina Holst C, Thiman L, Ekström G, et al. 5-HT2B receptor antagonists attenuate myofibroblast differentiation and subsequent fibrotic responses in vitro and in vivo. Physiol Rep 20164:.
Janssen W, Schymura Y, Novoyatleva T, Kojonazarov B, Boehm M, Wietelmann A, et al. 5-HT2B receptor antagonists inhibit fibrosis and protect from RV heart failure. Biomed Res Int 2015;2015:1–9.
Fletcher PJ, Rizos Z, Noble K, Soko AD, Silenieks LB, Lê AD, et al. Effects of the 5-HT2C receptor agonist Ro60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement. Neuropharmacology 2012;62:2288–98.
Kondaurova EM, Naumenko VS, Popova NK. Effect of chronic activation of 5-HT3 receptors on 5-HT3, 5-HT(1A) and 5-HT(2A) receptors functional activity and expression of key genes of the brain serotonin system. Neurosci Lett 2012;522:52–6.
Ohno Y, Imaki J, Mae Y, Takahashi T, Tatara A. Serotonergic modulation of extrapyramidal motor disorders in mice and rats: role of striatal 5-HT3 and 5-HT6 receptors. Neuropharmacology 2011;60:201–8.
Ortega JE, Mendiguren A, Pineda J, Meana JJ. Regulation of central noradrenergic activity by 5-HT(3) receptors located in the locus coeruleus of the rat. Neuropharmacology 2012;62:2472–9.
Kovac AL. Comparative pharmacology and guide to the use of the serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting. Drugs 2016;76:1719–35.
Lennertz L, Wagner M, Grabe HJ, Franke PE, Guttenthaler V, Rampacher F, et al. 5-HT3 receptor influences the washing phenotype and visual organization in obsessive-compulsive disorder supporting 5-HT3 receptor antagonists as novel treatment option. Eur Neuropsychopharmacol 2014;24:86–94.
Berthouze M, Rivail L, Lucas A, Ayoub MA, Russo O, Sicsic S, et al. Two transmembrane Cys residues are involved in 5-HT4 receptor dimerization. Biochem Biophys Res Commun 2007;356:642–7.
Licht CL, Knudsen GM, Sharp T. Effects of the 5-HT(4) receptor agonist RS67333 and paroxetine on hippocampal extracellular 5-HT levels. Neurosci Lett 2010;476:58–61.
Grailhe R, Grabtree GW, Hen R. Human 5-HT(5) receptors: the 5-HT(5A) receptor is functional but the 5-HT(5B) receptor was lost during mammalian evolution. Eur J Pharmacol 2001;418:157–67.
McCorvy JD, Roth BL. Structure and function of serotonin G protein-coupled receptors. Pharmacol Ther 2015;150:129–42.
Ferrero H, Solas M, Francis PT, Ramirez MJ. Serotonin 5-HT6 receptor antagonists in Alzheimer’s disease: therapeutic rationale and current development status. CNS Drugs 2017;31:19–32.
Heal DJ, Smith SL, Fisas A, Codony X, Buschmann H. Selective 5-HT6 receptor ligands: progress in the development of a novel pharmacological approach to the treatment of obesity and related metabolic disorders. Pharmacol Ther 2008;117:207–31.
Monti JM, Jantos H, Schechter LE. The effects of systemic and local microinjection into the central nervous system of the selective serotonin 5-HT6 receptor agonist WAY-208466 on sleep and wakefulness in the rat. Behav Brain Res 2013;249:65–74.
Monti JM, Jantos H. Effects of the 5-HT6 receptor antagonists SB-399885 and RO-4368554 and of the 5-HT(2A) receptor antagonist EMD 281014 on sleep and wakefulness in the rat during both phases of the light-dark cycle. Behav Brain Res 2011;216:381–8.
de Bruin NMWJ, McCreary AC, van Loevezijn A, de Vries TJ, Venhorst J, van Drimmelen M, et al. A novel highly selective 5-HT6 receptor antagonist attenuates ethanol and nicotine seeking but does not affect inhibitory response control in Wistar rats. Behav Brain Res 2013;236:157–65.
Horisawa T, Nishikawa H, Toma S, Ikeda A, Horiguchi M, Ono M, et al. The role of 5-HT7 receptor antagonism in the amelioration of MK-801-induced learning and memory deficits by the novel atypical antipsychotic drug lurasidone. Behav Brain Res 2013;244:66–9.
Nikiforuk A, Popik P. Amisulpride promotes cognitive flexibility in rats: the role of 5-HT7 receptors. Behav Brain Res 2013;248:136–40.
Ulugol A, Oltulu C, Gunduz O, Citak C, Carrara R, Shaqaqi MR, et al. 5-HT7 receptor activation attenuates thermal hyperalgesia in streptozocin-induced diabetic mice. Pharmacol Biochem Behav 2012;102:344–8.
Albayrak A, Halici Z, Cadirci E, Polat B, Karakus E, Bayir Y, et al. Inflammation and peripheral 5-HT7 receptors: the role of 5-HT7 receptors in carrageenan induced inflammation in rats. Eur J Pharmacol 2013;715:270–9.
Yang Z, Liu X, Yin Y, Sun S, Deng X. Involvement of 5-HT7 receptors in the pathogenesis of temporal lobe epilepsy. Eur J Pharmacol 2012;685:52–8.
Barbanti P, Aurilia C, Egeo G, Fofi L, Palmirotta R. Serotonin receptor targeted therapy for migraine treatment: an overview of drugs in phase I and II clinical development. Expert Opin Investig Drugs 2017;1-9.
Fitzgerald KT, Bronstein AC. Selective serotonin reuptake inhibitor exposure. Top Companion Anim Med 2013;28:13–7.
Mourilhe P, Stokes PE. Risks and benefits of selective serotonin reuptake inhibitors in the treatment of depression. Drug Saf 1998;18:57–82.
Nelson LS, Lewin NA, Howland MA, Hoffman RS, Goldfrank LR, Flomenbaum NE. Goldfrank’s toxicologic emergencies. 10th ed. McGraw-Hill Education; 2015.
Thomas DE, Lee JA, Hovda LR. Retrospective evaluation of toxicosis from selective serotonin reuptake inhibitor antidepressants: 313 dogs (2005-2010). J Vet Emerg Crit Care (San Antonio) 2012;22:674–81.
Woolf AD, Erdman AR, Nelson LS, Caravati EM, Cobaugh DJ, Booze LL, et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila) 2007;45:203–33.
Klint T, Helsdingen JT. Lack of typical SSRI-related adverse effects and sexual dysfunction with mirtazapine is related to specific blockade of 5-HT2 and 5-HT3 receptors. Eur Psychiatry 1996;11:347s.
Nebhinani N. Sertraline-induced galactorrhea: case report and review of cases reported with other SSRIs. Gen Hosp Psychiatry 2013;35(576):e3–e35.
Ho HY, Kam K-WA, Young AL, Chan LK, Yu EC-S. Acute angle closure glaucoma after sertraline. Gen Hosp Psychiatry 2013;35(575):e1–2.
Uguz F, Sonmez EÖ. Neuroleptic malignant syndrome following combination of sertraline and paroxetine: a case report. Gen Hosp Psychiatry 201335:327. e7-327. e8.
Hogg S, Dalvi A. Acceleration of onset of action in schedule-induced polydipsia: combinations of SSRI and 5-HT1A and 5-HT1B receptor antagonists. Pharmacol Biochem Behav 2004;77:69–75.
Fagiolini A, Comandini A, Catena Dell’Osso M, Kasper S. Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs 2012;26:1033–49.
Papakostas GI, Fava M. A meta-analysis of clinical trials comparing the serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. Eur Psychiatry 2007;22:444–7.
Zaniewska M, McCreary AC, Wydra K, Filip M. Effects of serotonin (5-HT)2 receptor ligands on depression-like behavior during nicotine withdrawal. Neuropharmacology 2010;58:1140–6.
Tarantino P, Appleton N, Lansdell K. Effect of trazodone on hERG channel current and QT-interval. Eur J Pharmacol 2005;510:75–85.
Ghanbari R, El Mansari M, Blier P. Electrophysiological impact of trazodone on the dopamine and norepinephrine systems in the rat brain. Eur Neuropsychopharmacol 2012;22:518–26.
Schreiber S, Backer MM, Herman I, Shamir D, Boniel T, Pick CG. The antinociceptive effect of trazodone in mice is mediated through both mu-opioid and serotonergic mechanisms. Behav Brain Res 2000;114:51–6.
Roth BL, Lopez E, Patel S, Kroeze WK. The multiplicity of serotonin receptors: uselessly diverse molecules or an embarrassment of riches? Neuroscientist 2000;6:252–62.
Fernández-Dueñas V, Poveda R, Fernández A, Sánchez S, Planas E, Ciruela F. Fentanyl-trazodone-paracetamol triple drug combination: multimodal analgesia in a mouse model of visceral pain. Pharmacol Biochem Behav 2011;98:331–6.
Stein MD, Kurth ME, Sharkey KM, Anderson BJ, Corso RP, Millman RP. Trazodone for sleep disturbance during methadone maintenance: a double-blind, placebo-controlled trial. Drug Alcohol Depend 2012;120:65–73.
Cheng W-M, Lin T-P, Lin ATL, Chen K-K, Chen T-J. A nationwide population study of trazodone use in urology patients. J Chin Med Assoc 2013;76:432–7.
Chang J-C, Wu Y-T, Lee W-C, Lin L-C, Tsai T-H. Herb-drug interaction of silymarin or silibinin on the pharmacokinetics of trazodone in rats. Chem Biol Interact 2009;182:227–32.
Ren Z, Chen S, Zhang J, Doshi U, Li AP, Guo L. Endoplasmic reticulum stress induction and ERK1/2 activation contribute to nefazodone-induced toxicity in hepatic cells. Toxicol Sci 2016;154:368–80.
Horst WD, Preskorn SH. Mechanisms of action and clinical characteristics of three atypical antidepressants: venlafaxine, nefazodone, bupropion. J Affect Disord 1998;51:237–54.
Gelenberg AJ, Trivedi MH, Rush AJ, Thase ME, Howland R, Klein DN, et al. Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Biol Psychiatry 2003;54:806–17.
Núñez M. Effects of nefazodone on voluntary ethanol consumption induced by isolation stress in young and aged rats. Pharmacol Biochem Behav 2002;73:689–96.
Goldberg JF. A preliminary open trial of nefazodone added to mood stabilizers for bipolar depression. J Affect Disord 2013;144:176–8.
Rush AJ, Armitage R, Gillin JC, Yonkers KA, Winokur A, Moldofsky H, et al. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry 1998;44:3–14.
Wiegand MH, Galanakis P, Schreiner R. Nefazodone in primary insomnia: an open pilot study. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:1071–8.
Freire-Garabal M, Varela M, Riveiro P, Balboa J, Liñares D, Mañá P, et al. Effects of nefazodone on the immune system of mice. Eur Neuropsychopharmacol 2000;10:255–64.
Agelink MW, Majewski T, Wurthmann C, Postert T, Linka T, Rotterdam S, et al. Autonomic neurocardiac function in patients with major depression and effects of antidepressive treatment with nefazodone. J Affect Disord 2001;62:187–98.
Brotto LA, Hanson LA, Gorzalka BB. Nefazodone attenuates the stress-induced facilitation of wet dog shaking behaviour but not the facilitation of sexual behaviour in female rats. Eur J Pharmacol 1999;381:101–4.
Przegaliński E, Lewandowska A. The effect of etoperidone, a new potential antidepressant drug, on the central serotonin system. J Neural Transm 1979;46:303–12.
Carruba MO, Parenti M, Ricciardi S, Picotti GB, Mantegazza P. Effect of etoperidone on the depletion of brain 5-hydroxytryptamine and catecholamines induced respectively by p-chloromethamphetamine and 6-hydroxydopamine in rats. Pharmacol Res Commun 1979;11:169–77.
Wu W, McKown LA. Hepatic in vitro metabolism of etoperidone, an antidepressant drug, in the rat and human. Chin Pharm J Taipei 2007;59:31.
Lisciani R, Baldini A, Benedetti D, Campana A, Barcellona PS. Acute cardiovascular toxicity of trazodone, etoperidone and imipramine in rats. Toxicology 1978;10:151–8.
Placheta P, Singer E, Kriwanek W, Mepiprazole Hertting G. a new psychotropic drug: effects on uptake and retention of monoamines in rat brain synaptosomes. Psychopharmacology (Berl) 1976;48:295–301.
Cohen ML, Fuller RW, Kurz KD. Evidence that blood pressure reduction by serotonin antagonists is related to alpha receptor blockade in spontaneously hypertensive rats. Hypertension 1983;5:676–81.
Maj J, Sypniewska M. Central action of mepiprazole. Pol J Pharmacol Pharm 1980;32:475–84.
Fuxe K, Agnati LF, Ungerstedt U. The effect of mepiprazole on central monoamine neurons: evidence for increased 5-hydroxytryptamine and dopamine receptor activity. Eur J Pharmacol 1976;35:93–108.
Fong MH, Garattini S, Caccia S. 1-m-Chlorophenylpiperazine is an active metabolite common to the psychotropic drugs trazodone, etoperidone and mepiprazole. J Pharm Pharmacol 1982;34:674–5.
Pullar IA, Carney SL, Colvin EM, Lucaites VL, Nelson DL, Wedley S. LY367265, an inhibitor of the 5-hydroxytryptamine transporter and 5-hydroxytryptamine(2A) receptor antagonist: a comparison with the antidepressant, nefazodone. Eur J Pharmacol 2000;407:39–46.
Wang S-J. Potential antidepressant LY 367265 presynaptically inhibits the release of glutamate in rat cerebral cortex. Synapse 2005;55:156–63.
Ozdemir E, Bagcivan I, Gursoy S, Altun A, Durmus N. Effects of fluoxetine and LY 367265 on tolerance to the analgesic effect of morphine in rats. Acta Physiol Hung 2011;98:205–13.
Bang-Andersen B, Ruhland T, Jørgensen M, Smith G, Frederiksen K, Jensen KG, et al. 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;54:3206–21.
Zhu XY, Etukala JR, Eyunni SVK, Setola V, Roth BL, Ablordeppey SY. 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;53:124–32.
Pessoa-Mahana H, González-Lira C, Fierro A, Zapata-Torres G, Pessoa-Mahana CD, Ortiz-Severin J, et al. Synthesis, docking and pharmacological evaluation of novel homo- and hetero-bis 3-piperazinylpropylindole derivatives at SERT and 5-HT1A receptor. Bioorg Med Chem 2013;21:7604–11.
Gomółka A, Ciesielska A, Wróbel MZ, Chodkowski A, Kleps J, Dawidowski M, et al. Novel 4-aryl-pyrido[1,2-c]pyrimidines with dual SSRI and 5-HT(1A) activity. Part 5. Eur J Med Chem 2015;98:221–36.
Stefanowicz J, Słowiński T, Wróbel MZ, Herold F, Gomółka AE, Wesołowska A, et al. Synthesis and biological investigation of new equatorial (β) stereoisomers of 3-aminotropane arylamides with atypical antipsychotic profile. Bioorg Med Chem 2016;24:3994–4007.
Ashby CR, Kehne JH, Bartoszyk GD, Renda MJ, Athanasiou M, Pierz KA, et al. Electrophysiological evidence for rapid 5-HT1A autoreceptor inhibition by vilazodone, a 5-HT1A receptor partial agonist and 5-HT reuptake inhibitor. Eur J Pharmacol 2013;714:359–65.
Heinrich T, Böttcher H, Gericke R, Bartoszyk GD, Anzali S, Seyfried CA, et al. 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;47:4684–92.
Hughes ZA, Starr KR, Langmead CJ, Hill M, Bartoszyk GD, Hagan JJ, et al. Neurochemical evaluation of the novel 5-HT1A receptor partial agonist/ serotonin reuptake inhibitor, vilazodone. Eur J Pharmacol 2005;510:49–57.
Page ME, Cryan JF, Sullivan A, Dalvi A, Saucy B, Manning DR, et al. Behavioral and neurochemical effects of 5-(4-[4-(5-Cyano-3-indolyl)-butyl)-butyl]-1-piperazinyl)-benzofuran-2-carboxamide (EMD 68843): a combined selective inhibitor of serotonin reuptake and 5-hydroxytryptamine(1A) receptor partial agonist. J Pharmacol Exp Ther 2002;302:1220–7.
Jain R, Chen D, Edwards J, Mathews M. Early and sustained improvement with vilazodone in adult patients with major depressive disorder: post hoc analyses of two phase III trials. Curr Med Res Opin 2014;30:263–70.
BRINTELLIX (vortioxetine). https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204447s000lbl.pdf (Accessed 17 July 2017).
Riga MS, Celada P, Sanchez C, Artigas F. P. 2. e. 003 Role of 5-HT3 receptors in the mechanism of action of the investigational antidepressant vortioxetine. Eur Neuropsychopharmacol 2013;23:S393–4.
Sanchez C. 863-Vortioxetine, an investigational antidepressant: implications of its multimodal mechanism of action in preclinical models of depression and cognitive function. Eur Psychiatry 2013;28:1.
Pehrson A, Li Y, Haddjeri N, Gulinello M, Sanchez C. P.1. g.014 Vortioxetine, a novel multimodal antidepressant, modulates GABA and glutamate neurotransmission via serotonergic mechanisms. Eur Neuropsychopharmacol 2013;23:S196–7.
du Jardin KG, Jensen JB, Sanchez C, Pehrson AL. Vortioxetine dose-dependently reverses 5-HT depletion-induced deficits in spatial working and object recognition memory: a potential role for 5-HT1A receptor agonism and 5-HT3 receptor antagonism. Eur Neuropsychopharmacol 2014;24:160–71.
Mørk A, Montezinho LP, Miller S, Trippodi-Murphy C, Plath N, Li Y, et al. Vortioxetine (Lu AA21004), a novel multimodal antidepressant, enhances memory in rats. Pharmacol Biochem Behav 2013;105:41–50.
Jensen JB, du Jardin KG, Song D, Budac D, Smagin G, Sanchez C, et al. Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation. Eur Neuropsychopharmacol 2014;24:148–59.
Keefe RSE, Mahableshwarkar AR, Olsen CK. P.2. f.013 Clinical evidence for improvement in cognitive dysfunction in patients with major depressive disorder (MDD) after treatment with vortioxetine. Eur Neuropsychopharmacol 2013;23:S402–3.
Angel I, Schoemaker H, Prouteau M, Garreau M, Langer SZ. Litoxetine: a selective 5-HT uptake inhibitor with concomitant 5-HT3 receptor antagonist and antiemetic properties. Eur J Pharmacol 1993;232:139–45.
Andrews M, Brown A, Chiva J-Y, Fradet D, Gordon D, Lansdell M, et al. Design and optimization of selective serotonin re-uptake inhibitors with high synthetic accessibility. Part 1. Bioorg Med Chem Lett 2009;19:2329–32.
Stolerman IP. Encyclopedia of psychopharmacology. Springer; 2010.
Dose Finding Study With Lu AA24530 in Major Depressive Disorder. https://clinicaltrials.gov/ct2/show/NCT00599911?term=Lu+AA24530&rank=1 (Accessed 17 July 2017).
Efficacy and Safety of Lu AA34893 in Patients With Bipolar Depression, https://clinicaltrials.gov/ct2/show/results/NCT00622245 (Accessed 17 July 2017).
Andreasen JT, Redrobe JP, Nielsen EØ. Combined α7 nicotinic acetylcholine receptor agonism and partial serotonin transporter inhibition produce antidepressant-like effects in the mouse forced swim and tail suspension tests: a comparison of SSR180711 and PNU-282987. Pharmacol Biochem Behav 2012;100:624–9.
Hayward A, Adamson L, Neill JC. Partial agonism at the α7 nicotinic acetylcholine receptor improves attention, impulsive action and vigilance in low attentive rats. Eur Neuropsychopharmacol 2017;27(4):325–35.
McClernon FJ, Hiott FB, Westman EC, Rose JE, Levin ED. Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial. Psychopharmacology (Berl) 2006;189:125–33.
Papakostas G, Ionescu D. Towards new mechanisms: an update on therapeutics for treatment-resistant major depressive disorder. Mol Psychiatry 2015;20:1142–50.
Murrough JW, Abdallah CG, Mathew SJ. Targeting glutamate signalling in depression: progress and prospects. Nat Rev Drug Discov 2017;16(7):472–86.
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Taciak, P.P., Lysenko, N. & Mazurek, A.P. Drugs which influence serotonin transporter and serotonergic receptors: Pharmacological and clinical properties in the treatment of depression. Pharmacol. Rep 70, 37–46 (2018). https://doi.org/10.1016/j.pharep.2017.07.011
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DOI: https://doi.org/10.1016/j.pharep.2017.07.011