Skip to main content Accessibility help
×
Home

Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors)

  • Stephen M. Stahl

Abstract

Vortioxetine is an antidepressant that targets multiple pharmacologic modes of action at sites—or nodes—where serotonergic neurons connect to various brain circuits. These multimodal pharmacologic actions of vortioxetine lead to enhanced release of various neurotransmitters, including serotonin, at various nodes within neuronal networks.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors)
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors)
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): enhancing serotonin release by combining serotonin (5HT) transporter inhibition with actions at 5HT receptors (5HT1A, 5HT1B, 5HT1D, 5HT7 receptors)
      Available formats
      ×

Copyright

References

Hide All
1. Stahl, SM. Classifying psychotropic drugs by mode of action and not by target disorder. CNS Spectr. 2013; 18(3): 113117.
2. Stahl, SM. Stahl’s Essential Psychopharmacology, 4th ed. Cambridge, UK: Cambridge University Press; 2013.
3. Zohar, J, Stahl, S, Moller, H-J, et al. Neuroscience Based Nomenclature. Cambridge, UK: Cambridge University Press; 2014.
4. Mork, A, Pehrson, A, Brennum, LT, et al. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther. 2012; 340(3): 666675.
5. Bang-Andersen, B, Ruhland, T, Jorgensen, M, 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(9): 32063221.
6. Areberg, J, Luntang-Jensen, M, Søgaard, B, Nilausen, . Occupancy of the serotonin transporter after administration of Lu AA21004 and its relation to plasma concentration in healthy subjects. Basic Clin Pharmacol Toxicol. 2012; 110(4): 401404.
7. Stahl, SM. Modes and nodes explain the mechanism of action of vortioxetine, a multi-modal agent (MMA): modifying serotonin’s downstream effects on glutamate and GABA (gamma-amino-butyric acid) release by blocking 5HT3 and 5HT7 receptors. CNS Spectr. In press.
8. Stahl, SM. Modes and nodes explain the mechanism of action of vortioxetine, a multi-modal agent (MMA): enhancing downstream release of neurotransmitters by blocking 5HT3 receptors. CNS Spectr. In press.
9. Stahl, SM. Modes and nodes explain the mechanism of action of vortioxetine, a multi-modal agent (MMA): enhancing downstream release of four pro-cognitive neurotransmitters by blocking 5HT1D receptors. CNS Spectr. In press.
10. Insel, T, Cuthbert, B, Garvey, M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010; 167(7): 748751.
11. Pehrson, AL, Sanchez, C. Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS Spectr. 2014; 19(2): 121133.
12. Pehrson, AL, Cremers, T, Betry, C, et al. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters—a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol. 2013; 23(2): 133145.
13. Fink, KB, Gothert, M. 5HT receptor regulation of neurotransmitter release. Pharmacol Rev. 2007; 59(4): 360417.
14. Assié, MB, Lomentach, H, Ravailhe, V, Faucillon, V, Newman-Tancredi, A. Rapid desensitization of somatodendritic 5HT1A receptors by chronic administration of the high-efficacy 5HT1A agonist, F13714: a microdialysis study in the rat. Br J Pharmacol. 2006; 149(2): 170178.
15. Gardier, AM, Malgie, I, Trillat, AC, Jacquot, C, Artigas, F. Role of 5HT1A autoreceptors in the mechanism of action of serotoninergic antidepressant drugs: recent findings from in vivo microdialysis studies. Fundam Clin Pharmacol. 1996; 10(1): 1627.
16. Romero, L, Ben, N, Artigas, F, De Montigny, C, Blier, P. Effect of pindolol on the function of pre- and postsynaptic 5HT1A receptors: in vivo microdialysis and electrophysiological studies in the rat brain. Neuropsychopharmacology. 1996; 15(4): 349360.
17. Sprouse, JS, Aghajanian, GK. Electrophysiological responses of serotoninergic dorsal raphe neurons to 5HT1A and 5HT1B agonists. Synapse. 1987; 1(1): 39.
18. Adell, A, Celada, P, Artigas, F. The role of 5HT1B receptors in the regulation of serotonin cell firing and release in the rat brain. J Neurochem. 2001; 79(1): 172182.
19. De Groote, L, Klompmakers, AA, Olivier, B, Westenberg, HG. Role of extracellular serotonin levels in the effect of 5HT1B receptor blockade. Psychopharmacology (Berl). 2003; 167(2): 153158.
20. Ruf, BM, Bhagwagar, Z. The 5HT1B receptor: a novel target for the pathophysiology of depression. Curr Drug Targets. 2009; 10(11): 11181138.
21. Sari, Y. Serotonin 1B receptors: from protein to physiological function and behavior. Neurosci Biobehav Rev. 2004; 28(6): 565582.
22. Sarkisyan, G, Roberts, AJ, Hedlund, PB. The 5HT7 receptor as a mediator and modulator of antidepressant-like behavior. Behav Brain Res. 2010; 209(1): 99108.
23. Bonaventure, P, Kelly, L, Aluisio, L, et al. Selective blockade of 5-hydroxytryptamine (5HT)7 receptors enhances 5HT neurotransmission, antidepressant-like behavior and rapid eye movement sleep suppression induced by citalopram in rodents. J Pharmacol Exp Ther. 2007; 321(2): 690698.
24. Stenkrona, P, Halldin, C, Lundberg, J. 5HTT and 5HT1A receptor occupancy of the novel substance vortioxetine (Lu AA21004). A PET study in control subjects. Eur Neuropsychopharmacol. 2013; 23(10): 11901198.
25. Meyer, JH. Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neuosci. 2007; 32(2): 86102.
26. Lundberg, J, Tiger, M, Landén, M, Halldin, C, Farde, L. Serotonin transporter occupancy with TCAs and SSRIs: a PET study in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012; 15(8): 11671172.
27. Meyer, JH, Wilson, AA, Sagrati, S, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an 11C-DASB positron emission tomography study. Am J Psychiatry. 2004; 161(5): 826835.
28. Citrome, L. Vortioxetine 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. 2014; 68(1): 6082.

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed