Vortioxetine
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| Systematic (IUPAC) name | |
|---|---|
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1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]piperazine | |
| Clinical data | |
| Trade names | Brintellix |
| Licence data | EMA:Link, US FDA:link |
| Pregnancy category |
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| Legal status |
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| Routes of administration | Oral |
| Pharmacokinetic data | |
| Bioavailability | 75% (peak at 7–11 hours) |
| Protein binding | 98% |
| Metabolism | extensive hepatic, primarily CYP2D6-mediated oxidation |
| Biological half-life | 66 hours |
| Excretion | 59% in urine, 26% in feces |
| Identifiers | |
| CAS Number |
508233-74-7  |
| ATC code | N06AX26 |
| PubChem | CID 9966051 |
| IUPHAR/BPS | 7351 |
| ChemSpider |
8141643  |
| KEGG |
D10184 |
| ChEBI |
CHEBI:76016 |
| Synonyms | Lu AA21004 |
| Chemical data | |
| Formula | C18H22N2S |
| Molar mass | 298.45 g/mol (379.36 as hydrobromide) |
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| (what is this?) (verify) | |
Vortioxetine (vor-tye-OKS-e-teen, trade name Brintellix (BRIN-tel-ix[1]) and Trintellix in Canada) is an atypical antidepressant (a serotonin modulator and stimulator) made by Lundbeck and Takeda.[2]
Medical use
Vortioxetine is used as first-line treatment for major depressive disorder.[2][3][4][5][6]
Side effects
The most common side effects reported with vortioxetine are nausea, diarrhea, dry mouth, constipation, vomiting, flatulence, dizziness, and sexual dysfunction.[2] Vortioxetine used alone in high dose or in combination with other medications, such as other antidepressants, can produce a potentially life-threatening drug reaction known as serotonin syndrome.[2]
Incidence of sexual dysfunction is reportedly higher in patients taking vortioxetine than in people taking placebos but appears to be lower than in people taking other antidepressants[2][6]
Pharmacodynamics
Vortioxetine is a so-called "serotonin modulator and stimulator".<ref name="urlLundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News">"Lundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News".</ref> It has been shown to possess the following pharmacological actions:[2][7][8]
- Serotonin transporter (SERT) blocker (i.e. serotonin reuptake inhibitor (SRI)) — Ki (binding affinity) = 1.6 nM, IC50 = 5.4 nM
- Norepinephrine transporter (NET) blocker — Ki = 113 nM
- 5-HT1A receptor high-efficacy partial agonist/near-full agonist — Ki = 15 nM, IA = 80%
- 5-HT1B receptor partial agonist — Ki = 33 nM
- 5-HT1D receptor antagonist — Ki = 54 nM
- 5-HT3A receptor antagonist — Ki = 3.7 nM
- 5-HT7 receptor antagonist — Ki = 19 nM
- β1-Adrenergic receptor ligand — Ki = 46 nM[7]
Pharmacokinetics
Vortioxetine reaches peak plasma concentration (Cmax) within 7 to 11 hours post-administration (Tmax), and its mean terminal half-life (t½) is ≈ 66 hours. Steady-state plasma concentrations are typically reached within two weeks.[2] It has no active metabolites (i.e. it is not a prodrug).[2]
Research
Vortioxetine has been studied in several clinical trials as a potential treatment for general anxiety disorder but results were inconsistent.[9][10]
History
Vortioxetine was discovered by scientists at Lundbeck who reported the rationale and synthesis for the drug (then called Lu AA21004) in a 2011 paper.[7][11]
In 2007, the compound was in Phase II clinical trials, and Lundbeck and Takeda entered into a partnership in which Takeda paid Lundbeck $40 million upfront, with promises of up to $345 million in milestone payments, and Takeda agreed to pay most of the remaining cost of developing the drug. The companies agreed to co-promote the drug in the US and Japan, and that Lundbeck would receive a royalty on all such sales. The deal included another drug candidate, tedatioxetine (Lu AA24530), and could be expanded to include two other Lundbeck compounds.[12]
Vortioxetine was approved by the U.S. FDA for the treatment of major depressive disorder (MDD) in adults in September, 2013,[13] and it was approved in Europe later that year.[14]
See also
- Tedatioxetine
- Paroxetine
- Buspar
- Vilazodone — a recently FDA-approved antidepressant with a similar dual mechanism of action.
References
- ↑ H. Lundbeck A/S (December 12, 2012). "FDA accepts Takeda and Lundbeck's filing for review of Brintellix (vortioxetine) for the treatment of major depression". Retrieved June 12, 2015.
- 1 2 3 4 5 6 7 8 US Label Last updated July 2014 after review in September, 2014. Versions of label are available at FDA index page Page accessed January 19, 2016
- ↑ [No authors listed] Vortioxetine. Aust Prescr. 2015 Jun;38(3):101-2. PMID 26648632 Free full text
- ↑ "Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies.". Curr Med Res Opin 30: 2589–606. Oct 10, 2014. doi:10.1185/03007995.2014.969566. PMID 25249164.
- ↑ Köhler S, Cierpinsky K, Kronenberg G, Adli M. The serotonergic system in the neurobiology of depression: Relevance for novel antidepressants. J Psychopharmacol. 2016 Jan;30(1):13-22. PMID 26464458
- 1 2 Kelliny M, Croarkin PE, Moore KM, Bobo WV. Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature. Ther Clin Risk Manag. 2015 Aug 12;11:1193-212. PMID 26316764 Free full text
- 1 2 3 Bang-Andersen B, Ruhland T, Jørgensen M, et al. (May 2011). "Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder". Journal of Medicinal Chemistry 54 (9): 3206–21. doi:10.1021/jm101459g. PMID 21486038.
- ↑ N. Moore; B. Bang-Andersen; L. Brennum; K. Fredriksen; S. Hogg; A. Mork; T. Stensbol; H. Zhong; C. Sanchez; D. Smith (August 2008). "Lu AA21004: a novel potential treatment for mood disorders". European Neuropsychopharmacology 18 (Supplement 4): S321. doi:10.1016/S0924-977X(08)70440-1.
- ↑ Pae CU et al. Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis. J Psychiatr Res. 2015 May;64:88-98. PMID 25851751
- ↑ Reinhold JA, Rickels K. Pharmacological treatment for generalized anxiety disorder in adults: an update. Expert Opin Pharmacother. 2015;16(11):1669-81. PMID 26159446
- ↑ Sanchez C, Asin KE, Artigas F Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data. Pharmacol Ther. 2015 Jan;145:43-57. PMID 25016186 Free full text
- ↑ Daniel Beaulieu for First Word Pharma. September 5th, 2007 Lundbeck, Takeda enter strategic alliance for mood disorder, anxiety drugs
- ↑ FDA approves new drug to treat major depressive disorder, U.S. Food and Drug Administration Press Announcement.
- ↑ EMA Brintellix page at EMA site Page accessed January 19, 2016
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