|
Vortioksetiini poikkeaa muista masennuslääkkeistä, siten, että se sekä vaikuttaa suoraan serotoniinireseptoreihin että estää serotoniinin takaisinottoa.<ref name=":2" /> Vaikka jotkut luokittelevat lääkkeen SSRI-lääkkeeksi,<ref name=":4" /> sen toimintamekanismi poikkeaa SSRI-lääkkeistä serotoniinireseptoreiden modulaation vuoksi.<ref name=":5" />
Tutkimusten perusteella vortioksetiini sitoutuu pääasiassa serotoniinin välittäjäaineeseenserotoniinitransporttereihin<!-- Mikä on oikea serotonin transporter suomennos? --> (SERT).<ref name=":5" /> Vortioksetiini vaikuttaa myös useisiin aivojen [[SerotoniinireseptoriAistinreseptori|serotoniinireseptoreihinreseptoreihin]].<ref name=":2" /> Se toimii 5-HT<sub>3</sub>, 5-HT<sub>1D</sub>, ja 5-HT<sub>7</sub> [[Antagonisti (lääketiede)|antagonistina]], 5-HT<sub>1A</sub> [[Agonisti|agonistina]], ja 5-HT<sub>1B</sub> osittaisena agonistina.<ref name=":5" /> Ei ole selvää vaikuttaako näihin reseptoreihin vaikuttaminen masennuksen hoidossa.<ref name=":2" /><ref name=":5" /> Puutteellinen 5-HT reseptorien toiminta on yhdistetty ahdistukseen ja pakkomielteisiin.<ref name=":7">{{Lehtiviite|Tekijä=Chantal Moret, Mike Briley|Otsikko=The importance of norepinephrine in depression|Julkaisu=Neuropsychiatric Disease and Treatment|Ajankohta=2011|Vuosikerta=7|Numero=Suppl 1|Sivut=9–13|Pmid=21750623|Doi=10.2147/NDT.S19619|Issn=1176-6328|www=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131098/}}</ref>
Joidenkin masennuslääkkeiden pitkäaikainen käyttö voi aiheuttaa 5-HT<sub>1A</sub> -reseptorin turtumista, joka johtaa negatiiviseen kierteeseen ja lääkehoidon tehon heikkenemiseen. Vortioksetiini toimii 5-HT<sub>1A</sub> -reseptorin agonistina, mikä saattaa nopeuttaa antidepressiivisia vaikutuksia. Annoksen nostaminen lisää lääkkeen sitoutumista 5-HT reseptoreihin 15 % jokaista 5 mg kohden.<ref name=":5" />
Vortioksetiinin on havaittu parantavan masentuneiden kognitiivisia taitoja.<ref>{{Verkkoviite|osoite=https://academic.oup.com/ijnp/article/17/10/1557/2356868|julkaisu=academic.oup.com|viitattu=2024-03-08}}</ref> 5-HT, noradrenaliinin ja asetyylikoliinin vapautuminen saattaa olla syynä myös kognitiivisten taitojen parantumiseen.<ref name=":6" /> Eläinkokeissa on havaittu 5-HT<sub>3</sub> -reseptorin antagonisoinnin vaikuttavan kognitiivisiin taitoihin.<ref>{{Lehtiviite|Tekijä=Amy F. T. Arnsten, C. Huie Lin, Christopher H. Van Dyck, Kelly J. Stanhope|Otsikko=The effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys|Julkaisu=Neurobiology of Aging|Ajankohta=1997-01-01|Vuosikerta=18|Numero=1|Sivut=21–28|Doi=10.1016/S0197-4580(96)00162-5|Issn=0197-4580|www=https://www.sciencedirect.com/science/article/pii/S0197458096001625}}</ref>
{| class="wikitable"
|+
!Reseptori
!Lääkkeen vaikutus
!Reseptorin säätelemät asiat kehossa<!-- Tehtävät kopioitu serotoniinireseptori sivulta lähteineen 8.3.2024 -->
|-
|5-HT<sub>1A</sub>
|agonisti (lisää)
|Riippuvuus <ref name="pmid7862892">{{cite journal|author=Tomkins DM, Higgins GA, Sellers EM|title=Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake|journal=Psychopharmacology (Berl).|volume=115|issue=1–2|pages=173–9|year=1994|pmid=7862892|doi=10.1007/BF02244769}}</ref><ref name="pmid17316955">{{cite journal|author=Müller CP, Carey RJ, Huston JP, De Souza Silva MA|title=Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors|journal=Prog Neurobiol.|volume=81|issue=3|pages=133–78|year=2007|pmid=17316955|doi=10.1016/j.pneurobio.2007.01.001}}</ref><ref name="pmid15713268">{{cite journal|author=Carey RJ, DePalma G, Damianopoulos E, Shanahan A, Müller CP, Huston JP|title=Evidence that the 5-HT1A autoreceptor is an important pharmacological target for the modulation of cocaine behavioral stimulant effects|journal=Brain Res.|volume=1034|issue=1–2|pages=162–71|year=2005|pmid=15713268|doi=10.1016/j.brainres.2004.12.012}}</ref>, Aggressio<ref name="pmid16310183">{{cite journal|author=de Boer SF, Koolhaas JM|title=5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis|journal=Eur J Pharmacol.|volume=526|issue=1–3|pages=125–39|year=2005|pmid=16310183|doi=10.1016/j.ejphar.2005.09.065}}</ref>, Hätääntyneisyys<ref name="pmid9724773">{{cite journal|author=Parks CL, Robinson PS, Sibille E, Shenk T, Toth M|title=Increased anxiety of mice lacking the serotonin1A receptor|journal=Proc Natl Acad Sci U S A.|volume=195|issue=18|pages=10734–9|year=1998|pmid=9724773|pmc=27964|doi=10.1073/pnas.95.18.10734}}</ref>, Ruokahalu<ref name="pmid17609739">{{cite journal|author=Ebenezer IS, Arkle MJ, Tite RM|title=8-Hydroxy-2-(di-n-propylamino)-tetralin inhibits food intake in fasted rats by an action at 5-HT1A receptors|journal=Methods Find Exp Clin Pharmacol.|volume=29|issue=4|pages=269–72|year=1998|pmid=17609739|doi=10.1358/mf.2007.29.4.1075362}}</ref>, Verenpaine<ref name="pmid2842163">{{cite journal|author=Wouters W, Tulp MT, Bevan P|title=Flesinoxan lowers blood pressure and heart rate in cats via 5-HT1A receptors|journal=Eur J Pharmacol.|volume=149|issue=3|pages=213–23|year=1998|pmid=2842163|doi=10.1016/0014-2999(88)90651-6}}</ref><ref name="pmid18667366">{{cite journal|author=Horiuchi J, McDowall LM, Dampney RA|title=Role of 5-HT(1A) receptors in the lower brainstem on the cardiovascular response to dorsomedial hypothalamus activation|journal=Auton Neurosci.|volume=142|issue=1–2|pages=71–6|year=2008|pmid=18667366|doi=10.1016/j.autneu.2008.06.004}}</ref>, Sydän<ref name="pmid15802554">{{cite journal|author=Nalivaiko E, Ootsuka Y, Blessing WW.|title=Activation of 5-HT1A receptors in the medullary raphe reduces cardiovascular changes elicited by acute psychological and inflammatory stresses in rabbits|journal=Am J Physiol Regul Integr Comp Physiol.|volume=289|issue=2|pages=R596–R604|year=2005|pmid=15802554|doi=10.1152/ajpregu.00845.2004}}</ref>, Oksentaminen<ref name="pmid8013549">{{cite journal|author=Lucot JB.|title=Antiemetic effects of flesinoxan in cats: comparisons with 8-hydroxy-2-(di-n-propylamino)tetralin|journal=Eur J Pharmacol.|volume=253|issue=1–2|pages=53–60|year=1994|pmid=8013549|doi=10.1016/0014-2999(94)90756-0}}</ref>, Sydämen lyöntitiheys<ref name="pmid2842163" /><ref name="pmid18667366" />, Impulsiivisuus<ref name="pmid15688093">{{cite journal|author=Winstanley CA, Theobald DE, Dalley JW, Robbins TW.|title=Interactions between serotonin and dopamine in the control of impulsive choice in rats: therapeutic implications for impulse control disorders|journal=Neuropsychopharmacology.|volume=30|issue=4|pages=669–682|year=2005|pmid=15688093|doi=10.1038/sj.npp.1300610}}</ref>, Muisti<ref name="pmid18394726">{{cite journal|author=Ogren SO, Eriksson TM, Elvander-Tottie E, D'Addario C, Ekström JC, Svenningsson P, Meister B, Kehr J, Stiedl O|title=The role of 5-HT(1A) receptors in learning and memory|journal=Behav Brain Res.|volume=195|issue=1|pages=54–77|year=2008|pmid=18394726|doi=10.1016/j.bbr.2008.02.023}}</ref><ref name="pmid12562581">{{cite journal|author=Yasuno F, Suhara T, Nakayama T, Ichimiya T, Okubo Y, Takano A, Ando T, Inoue M, Maeda J, Suzuki K|title=Inhibitory effect of hippocampal 5-HT1A receptors on human explicit memory|journal=Am J Psychiatry|volume=160|issue=2|pages=334–40|year=2003|pmid=12562581|doi=10.1176/appi.ajp.160.2.334}}</ref>, Mieliala<ref name="pmid2883013">{{cite journal|author=Kennett GA, Dourish CT, Curzon G|title=Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression|journal=Eur J Pharmacol.|volume=134|issue=3|pages=265–74|year=1987|pmid=2883013|doi=10.1016/0014-2999(87)90357-8}}</ref>, Pahoinvointi<ref name="pmid8013549" />, Haitalliset ärsykkeet<ref name="pmid12595749">{{cite journal|author=Bardin L, Tarayre JP, Malfetes N, Koek W, Colpaert FC.|title=Profound, non-opioid analgesia produced by the high-efficacy 5-HT(1A) agonist F 13640 in the formalin model of tonic nociceptive pain|journal=Pharmacology.|volume=67|issue=4|pages=182–194|year=2003|pmid=12595749|doi=10.1159/000068404}}</ref>, Siittimen erektio<ref name="pmid9085055">{{cite journal|author=Millan MJ, Perrin-Monneyron S|title=Potentiation of fluoxetine-induced penile erections by combined blockade of 5-HT1A and 5-HT1B receptors|journal=Eur J Pharmacol.|volume=321|issue=3|pages=11–3|year=1997|pmid=9085055|doi=10.1016/S0014-2999(97)00050-2}}</ref>, Pupillin laajeneminen<ref name="pmid8982715">{{cite journal|author=Prow MR, Martin KF, Heal DJ|title=8-OH-DPAT-induced mydriasis in mice: a pharmacological characterisation|journal=Eur J Pharmacol.|volume=317|issue=1|pages=21–8|year=1996|pmid=8982715|doi=10.1016/S0014-2999(96)00693-0}}</ref>, Hengitys<ref name="pmid16166206">{{cite journal|author=Meyer LC, Fuller A, Mitchell D|title=Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats|journal=American Journal of Physiology. Regulatory, Integrative and Comparative Physiology|volume=290|issue=2|pages=R405–13|year=2006|month=February|pmid=16166206|doi=10.1152/ajpregu.00440.2005|url=|issn=}}</ref>, Seksuaalinen käytös<ref name="pmid11965359">{{cite journal|author=Popova NK, Amstislavskaya TG|title=Involvement of the 5-HT(1A) and 5-HT(1B) serotonergic receptor subtypes in sexual arousal in male mice|journal=Psychoneuroendocrinology|volume=27|issue=5|pages=609–18|year=2002|pmid=11965359|doi=10.1016/S0306-4530(01)00097-X}}</ref>, Uni<ref name="pmid10607047">{{cite journal|author=Monti JM, Jantos H|title=Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat|journal=J Sleep Res.|volume=1|issue=3|pages=169–175|year=1992|pmid=10607047|doi=10.1111/j.1365-2869.1992.tb00033.x}}</ref>, Sosiaalisuus<ref name="pmid17383105">{{cite journal|author=Thompson MR, Callaghan PD, Hunt GE, Cornish JL, McGregor IS|title=A role for oxytocin and 5-HT(1A) receptors in the prosocial effects of 3,4 methylenedioxymethamphetamine ("ecstasy")|journal=Neuroscience|volume=146|issue=2|pages=509–14|year=2007|pmid=17383105|doi=10.1016/j.neuroscience.2007.02.032}}</ref>, Lämmönsäätely<ref name="pmid2951611">{{cite journal|author=Gudelsky GA, Koenig JI, Meltzer HY|title=Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors|journal=Neuropharmacology|volume=25|issue=12|pages=1307–13|year=1986|pmid=2951611|doi=10.1016/0028-3908(86)90101-2}}</ref>, Verisuonten supistuminen<ref name="pmid16455061">{{cite journal|author=Ootsuka Y, Blessing WW.|title=Activation of 5-HT1A receptors in rostral medullary raphé inhibits cutaneous vasoconstriction elicited by cold exposure in rabbits|journal=Brain Res.|volume=1073-1074|pages=252–61|year=2006|pmid=16455061|doi=10.1016/j.brainres.2005.12.031}}</ref>
|-
|5-HT<sub>1B</sub>
|osittainen agonisti (lisää)
|Riippuvuus <ref name="pmid10027505">{{cite journal|author=Harrison AA, Parsons LH, Koob GF, Markou A|title=RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist|journal=Psychopharmacology (Berl).|volume=141|issue=3|pages=242–50|year=1999|pmid=10027505|doi=10.1007/s002130050831}}</ref>, Aggressio<ref name="pmid163101832">{{cite journal|author=de Boer SF, Koolhaas JM|title=5-HT1A and 5-HT1B receptor agonists and aggression: a pharmacological challenge of the serotonin deficiency hypothesis|journal=Eur J Pharmacol.|volume=526|issue=1–3|pages=125–39|year=2005|pmid=16310183|doi=10.1016/j.ejphar.2005.09.065}}</ref>, Hätääntyneisyys<ref name="pmid15720791">{{cite journal|author=Chojnacka-Wójcik E, Klodzinska A, Tatarczynska E|title=The anxiolytic-like effect of 5-HT1B receptor ligands in rats: a possible mechanism of action|journal=J Pharm Pharmacol.|volume=57|issue=2|pages=253–7|year=2005|pmid=15720791|doi=10.1211/0022357055399}}</ref><ref name="pmid11888549">{{cite journal|author=Lin D, Parsons LH|title=Anxiogenic-like effect of serotonin(1B) receptor stimulation in the rat elevated plus-maze|journal=Pharmacol Biochem Behav.|volume=71|issue=4|pages=581–7|year=2002|pmid=11888549|doi=10.1016/S0091-3057(01)00712-2}}</ref><ref name="pmid15577451">{{cite journal|author=Tatarczynska E, Klodzinska A, Stachowicz K, Chojnacka-Wójcik E|title=Effects of a selective 5-HT1B receptor agonist and antagonists in animal models of anxiety and depression|journal=Behav Pharmacol.|volume=15|issue=8|pages=523–34|year=2004|pmid=15577451|doi=10.1097/00008877-200412000-00001}}</ref>, Oppiminen<ref name="pmid18394658">{{cite journal|author=Eriksson TM, Madjid N, Elvander-Tottie E, Stiedl O, Svenningsson P, Ogren SO|title=Blockade of 5-HT 1B receptors facilitates contextual aversive learning in mice by disinhibition of cholinergic and glutamatergic neurotransmission|journal=Neuropharmacology|volume=54|issue=7|pages=1041–50|year=2008|pmid=18394658|doi=10.1016/j.neuropharm.2008.02.007}}</ref>, Liikkeet<ref name="pmid10454466">{{cite journal|author=McCreary AC, Bankson MG, Cunningham KA|title=Pharmacological studies of the acute and chronic effects of (+)-3, 4-methylenedioxymethamphetamine on locomotor activity: role of 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B/1D) receptors|journal=J Pharmacol Exp Ther.|volume=290|issue=3|pages=965–73|year=1999|pmid=10454466}}</ref>, Muisti<ref name="pmid18394658" />, Mieliala<ref name="pmid15577451" />, Siittimen erektio<ref name="pmid90850552">{{cite journal|author=Millan MJ, Perrin-Monneyron S|title=Potentiation of fluoxetine-induced penile erections by combined blockade of 5-HT1A and 5-HT1B receptors|journal=Eur J Pharmacol.|volume=321|issue=3|pages=11–3|year=1997|pmid=9085055|doi=10.1016/S0014-2999(97)00050-2}}</ref>, Seksuaalinen käytös<ref name="pmid119653592">{{cite journal|author=Popova NK, Amstislavskaya TG|title=Involvement of the 5-HT(1A) and 5-HT(1B) serotonergic receptor subtypes in sexual arousal in male mice|journal=Psychoneuroendocrinology|volume=27|issue=5|pages=609–18|year=2002|pmid=11965359|doi=10.1016/S0306-4530(01)00097-X}}</ref>, Verisuonten supistuminen
|-
|5-HT<sub>1D</sub>
|antagonisti (vähentää)
|Hätääntyneisyys<ref name="pmid15820416">{{cite journal|author=Amital D, Fostick L, Sasson Y, Kindler S, Amital H, Zohar J|title=Anxiogenic effects of Sumatriptan in panic disorder: a double-blind, placebo-controlled study|journal=Eur Neuropsychopharmacol.|volume=15|issue=3|pages=279–82|year=2005|pmid=15820416|doi=10.1016/j.euroneuro.2004.12.002}}</ref><ref name="pmid8736648">{{cite journal|author=Feuerstein TJ, Hüring H, van Velthoven V, Lücking CH, Landwehrmeyer GB|title=5-HT1D-like receptors inhibit the release of endogenously formed [3H]GABA in human, but not in rabbit, neocortex|journal=Neurosci Lett.|volume=209|issue=3|pages=210–4|year=1996|pmid=8736648|doi=10.1016/0304-3940(96)12637-9}}</ref>, Liikkeet<ref name="pmid104544662">{{cite journal|author=McCreary AC, Bankson MG, Cunningham KA|title=Pharmacological studies of the acute and chronic effects of (+)-3, 4-methylenedioxymethamphetamine on locomotor activity: role of 5-hydroxytryptamine(1A) and 5-hydroxytryptamine(1B/1D) receptors|journal=J Pharmacol Exp Ther.|volume=290|issue=3|pages=965–73|year=1999|pmid=10454466}}</ref>, Verisuonten supistuminen
|-
|5-HT<sub>3</sub>
|antagonisti (vähentää)
|Riippuvuus, Hätääntyneisyys, Oksentaminen, Ruoansulatuskanavan liikkuvuus{{Lähde|pyydetty=22.11.2023}}, Oppiminen<ref name="pmid8115433">{{cite journal|author=Pitsikas N, Brambilla A, Borsini F.|title=Effect of DAU 6215, a novel 5-HT3 receptor antagonist, on scopolamine-induced amnesia in the rat in a spatial learning task|journal=Pharmacol Biochem Behav.|volume=47|issue=1|pages=95–99|year=1994|pmid=8115433|doi=10.1016/0091-3057(94)90116-3}}</ref>, Muisti<ref name="pmid8115433" />, Pahoinvointi
|-
|5-HT<sub>7</sub>
|antagonisti (vähentää)
|Hätääntyneisyys<ref name="pmid16018977">{{cite journal|author=Hedlund PB, Huitron-Resendiz S, Henriksen SJ, Sutcliffe JG|title=5-HT7 receptor inhibition and inactivation induce antidepressantlike behavior and sleep pattern|journal=Biological Psychiatry|volume=58|issue=10|pages=831–7|year=2005|month=November|pmid=16018977|doi=10.1016/j.biopsych.2005.05.012|url=|issn=}}</ref><ref name="pmid16828124">{{cite journal|author=Wesolowska A, Nikiforuk A, Stachowicz K, Tatarczynska E|title=Effect of the selective 5-HT7 receptor antagonist SB 269970 in animal models of anxiety and depression|journal=Neuropharmacology|volume=51|issue=3|pages=578–86|year=2006|month=September|pmid=16828124|doi=10.1016/j.neuropharm.2006.04.017|url=|issn=}}</ref>, Muisti<ref name="pmid18308404">{{cite journal|author=Gasbarri A, Cifariello A, Pompili A, Meneses A|title=Effect of 5-HT(7) antagonist SB-269970 in the modulation of working and reference memory in the rat|journal=Behavioural Brain Research|volume=195|issue=1|pages=164–70|year=2008|month=December|pmid=18308404|doi=10.1016/j.bbr.2007.12.020|url=|issn=}}</ref><ref name="pmid18570192">{{cite journal|author=Liy-Salmeron G, Meneses A|title=Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model|journal=Hippocampus|volume=18|issue=9|pages=965–74|year=2008|pmid=18570192|doi=10.1002/hipo.20459|url=|issn=}}</ref>, Mieliala<ref name="pmid16018977" /><ref name="pmid16828124" />, Hengitys<ref name="pmid161662061">{{cite journal|author=Meyer LC, Fuller A, Mitchell D|title=Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats|journal=Am J Physiol Regul Integr Comp Physiol.|volume=290|issue=2|pages=405–13|year=2006|pmid=16166206|doi=10.1152/ajpregu.00440.2005}}</ref><ref name="pmid17314195">{{cite journal|author=Bonaventure P, Kelly L, Aluisio L, Shelton J, Lord B, Galici R, Miller K, Atack J, Lovenberg TW, Dugovic C|title=Selective blockade of 5-hydroxytryptamine (5-HT)7 receptors enhances 5-HT transmission, antidepressant-like behavior, and rapid eye movement sleep suppression induced by citalopram in rodents|journal=J Pharmacol Exp Ther.|volume=321|issue=2|pages=690–8|year=2007|pmid=17314195|doi=10.1124/jpet.107.119404}}</ref>, Uni<ref name="pmid16018977" /><ref name="pmid17314195" /><ref name="pmid12812993">{{cite journal|author=Thomas DR, Melotto S, Massagrande M, Gribble AD, Jeffrey P, Stevens AJ, Deeks NJ, Eddershaw PJ, Fenwick SH, Riley G, Stean T, Scott CM, Hill MJ, Middlemiss DN, Hagan JJ, Price GW, Forbes IT|title=SB-656104-A, a novel selective 5-HT7 receptor antagonist, modulates REM sleep in rats|journal=Br J Pharmacol.|volume=139|issue=4|pages=705–14|year=2003|pmid=12812993|doi=10.1038/sj.bjp.0705290|pmc=1573887}}</ref>, Lämmönsäätely, Verisuonten supistuminen
|}
== Tutkimukset ja lääkelupa ==
|
