Vortioxetine , sold under the trade names Trintellix among others, is a medication used to treat major depressive disorder .[ 3] Effectiveness is viewed as similar to that of other antidepressants .[ 3] It is only recommended in people who have not improved sufficiently on two other antidepressants.[ 4] It is taken by mouth.[ 3]
Common side effects include constipation and nausea .[ 3] Serious side effects may include suicide in those under the age of 25, serotonin syndrome , bleeding, mania , and SIADH .[ 3] A withdrawal syndrome may occur if the dose is rapidly decreased.[ 3] Use during pregnancy and breastfeeding is not generally recommended.[ 4] It is classified as a serotonin modulator .[ 3] How it works is not entirely clear but is believed to be related to increasing serotonin levels.[ 3]
It was approved for medical use in the United States in 2013.[ 3] A month supply in the United Kingdom costs the NHS about £27.72 as of 2019.[ 4] In the United States the wholesale cost of this amount is about 368.40 USD.[ 5] In 2016 it was the 260th most prescribed medication in the United States with more than a million prescriptions.[ 6]
Medical uses
Vortioxetine is used as a treatment for major depressive disorder .[ 3] Effectiveness appear to be similar to other antidepressants .[ 3] It may be used when other treatments have failed.[ 7] [ 8] [ 9] [ 10]
Vortioxetine is also used off label for anxiety .[ 11] A 2016 review found it was not useful in generalized anxiety disorder .[ 12]
Adverse effects
The most common side effects reported with vortioxetine are nausea , diarrhea , dry mouth , constipation , vomiting , flatulence , dizziness , and sexual dysfunction .[ 7] However, with the singular exception of nausea, these side effects occurred in less than 10% of study participants given the active drug, with up to 8% of placebo-treated participants reporting the same side effects.
If Vortioxetine is prescribed alongside traditional selective serotonin reuptake inhibitors (SSRIs), or other serotonergic drugs, this can induce the potentially life-threatening serotonin syndrome .[ 7]
Incidence of sexual dysfunction is only slightly higher in patients taking vortioxetine than in people taking placebos and occurs in less than 10% of vortioxetine-treated patients. As such, vortioxetine may be appropriate for people who have suffered sexual side effects from other antidepressant medications.[ 7] [ 10]
Pharmacology
Pharmacodynamics
It increases serotonin concentrations in the brain by inhibiting its reuptake in the synapse , and by modulating (activating certain receptors while blocking, or antagonizing, others) certain serotonin receptors . This puts it in the class of atypical antidepressants known as serotonin modulators and stimulators .
Vortioxetine is a serotonin modulator and stimulator like vilazodone .[ 13] It has been shown to possess the following pharmacological actions:[ 7] [ 14] [ 15] [ 16] [ 17] [ 18]
Target
Affinity
Functional activity
Action
Ki (nM)
IC50 / EC50 (nM)
IA (%)
SERT Tooltip Serotonin transporter *
1.6
5.4
—
Inhibition
NET Tooltip Norepinephrine transporter *
113
—
—
Inhibition
5-HT1A *
15
200
96
Agonist
5-HT1B *
33
120
55
Partial agonist
5-HT1D *
54
370
—
Antagonist
5-HT3 *
3.7
12
—
Antagonist
5-HT7 *
19
450
—
Antagonist
β1
46[ 14]
—
—
—
* Human isoforms
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 mean Cmax values were 9, 18, and 33 ng/mL following doses of 5, 10, and 20 mg/day. Steady-state plasma concentrations are typically reached within two weeks.[ 7]
Vortioxetine's pKa values are determined to be 9.1 (± 0.1) and 3.0 (± 0.2) according to Australian Public Assessment Report for vortioxetine hydrobromide.[ 19]
History
10 mg tablets of vortioxetine (Trintellix).
Vortioxetine was discovered by scientists at Lundbeck who reported the rationale and synthesis for the drug (then called Lu AA21004) in a 2011 paper.[ 14] [ 20]
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.[ 21]
Vortioxetine was approved by the U.S. FDA for the treatment of major depressive disorder (MDD) in adults in September 2013,[ 22] and it was approved in Europe later that year.[ 23]
Society and culture
It is made by the pharmaceutical companies Lundbeck and Takeda .[ 7]
Names
Vortioxetine was previously trademarked as Brintellix in the United States, but on May 2, 2016, the US FDA approved a name change to Trintellix in order to avoid confusion with the blood-thinning medication Brilinta (ticagrelor ).[ 24]
References
^ "TGA eBS - Product and Consumer Medicine Information Licence" . www.ebs.tga.gov.au . Archived from the original on 29 April 2018. Retrieved 29 April 2018 .
^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)" . nctr-crs.fda.gov . FDA . Retrieved 22 Oct 2023 .
^ a b c d e f g h i j k "Vortioxetine Hydrobromide Monograph for Professionals" . Drugs.com . American Society of Health-System Pharmacists. Retrieved 18 March 2019 .
^ a b c British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 376. ISBN 9780857113382 .
^ "NADAC as of 2019-02-27" . Centers for Medicare and Medicaid Services . Retrieved 3 March 2019 .
^ "The Top 300 of 2019" . clincalc.com . Retrieved 22 December 2018 .
^ a b c d e f g US Label Archived 2016-01-31 at the Wayback Machine Last updated July 2014 after review in September, 2014. Versions of label are available at FDA index page Page accessed January 19, 2016
^ Connolly, KR; Thase, ME (2016). "Vortioxetine: a New Treatment for Major Depressive Disorder". Expert Opinion on Pharmacotherapy . 17 (3): 421–31. doi :10.1517/14656566.2016.1133588 . PMID 26679430 . The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option.
^ 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. doi :10.1177/0269881115609072 PMID 26464458
^ a b 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. doi :10.2147/TCRM.S55313 PMID 26316764 Free full text Archived 2018-04-29 at the Wayback Machine
^ Pae, Chi-Un; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A.; Masand, Praksh S.; Serretti, Alessandro (May 2015). "Vortioxetine, a multimodal antidepressant for generalized anxiety disorder: a systematic review and meta-analysis". Journal of Psychiatric Research . 64 : 88–98. doi :10.1016/j.jpsychires.2015.02.017 . ISSN 1879-1379 . PMID 25851751 .
^ Fu, Jie; Peng, Lilei; Li, Xiaogang (2016-04-19). "The efficacy and safety of multiple doses of vortioxetine for generalized anxiety disorder: a meta-analysis" . Neuropsychiatric Disease and Treatment . 12 : 951–959. doi :10.2147/NDT.S104050 . ISSN 1176-6328 . PMC 4844447 . PMID 27143896 . {{cite journal }}
: CS1 maint: unflagged free DOI (link )
^ "Lundbeck's "Serotonin Modulator and Stimulator" Lu AA21004: How Novel? How Good? - GLG News" . Archived from the original on 2011-07-24.
^ a b c 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 .
^ Sanchez, C; Asin, KE; Artigas, F (1 January 2015). "Vortioxetine, a Novel Antidepressant with Multimodal Activity: Review of Preclinical and Clinical Data". Pharmacology & Therapeutics . 145 : 43–57. doi :10.1016/j.pharmthera.2014.07.001 . ISSN 1879-016X . PMID 25016186 .
^ Stahl, Stephen M. (2013-04-11). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4th ed.). Cambridge University Press. ISBN 978-1107686465 .
^ "BindingDB Search: BDBM50400902 1-(2-(2,4-dimethylphenylsulfanyl)phenyl)piperazine" . BindingDB . Retrieved 7 December 2018 .
^ "Australian Public Assessment Report for vortioxetine hydrobromide" (PDF) . p. 11. Archived from the original (PDF) on 2017-08-01. Retrieved 2018-05-05 .
^ Sanchez, C; Asin, KE; Artigas, F (2015). "Vortioxetine, a novel antidepressant with multimodal activity: review of preclinical and clinical data". Pharmacol. Ther . 145 : 43–57. doi :10.1016/j.pharmthera.2014.07.001 . PMID 25016186 .
^ Daniel Beaulieu for First Word Pharma. September 5th, 2007 Lundbeck, Takeda enter strategic alliance for mood disorder, anxiety drugs Archived 2016-10-10 at the Wayback Machine
^ FDA approves new drug to treat major depressive disorder Archived 2013-10-03 at the Wayback Machine , U.S. Food and Drug Administration Press Announcement.
^ EMA Brintellix page at EMA site Archived 2016-01-26 at the Wayback Machine Page accessed January 19, 2016
^ Commissioner, Office of the. "Safety Alerts for Human Medical Products - Brintellix (vortioxetine): Drug Safety Communication - Brand Name Change to Trintellix, to Avoid Confusion With Antiplatelet Drug Brilinta (ticagrelor)" . www.fda.gov . Archived from the original on 2016-05-05. Retrieved 2016-05-02 .
SSRIs Tooltip Selective serotonin reuptake inhibitors SNRIs Tooltip Serotonin–norepinephrine reuptake inhibitors NRIs Tooltip Norepinephrine reuptake inhibitors NDRIs Tooltip Norepinephrine–dopamine reuptake inhibitors NaSSAs Tooltip Noradrenergic and specific serotonergic antidepressants SARIs Tooltip Serotonin antagonist and reuptake inhibitors SMS Tooltip Serotonin modulator and stimulators Others
TCAs Tooltip Tricyclic antidepressants TeCAs Tooltip Tetracyclic antidepressants Others
Non-selective MAOA Tooltip Monoamine oxidase A -selectiveMAOB Tooltip Monoamine oxidase B -selective
DAT Tooltip Dopamine transporter (DRIs Tooltip Dopamine reuptake inhibitors )
NET Tooltip Norepinephrine transporter (NRIs Tooltip Norepinephrine reuptake inhibitors )
Others: Antihistamines (e.g., brompheniramine , chlorphenamine , pheniramine , tripelennamine )
Antipsychotics (e.g., loxapine , ziprasidone )
Arylcyclohexylamines (e.g., ketamine , phencyclidine )
Dopexamine
Ephenidine
Ginkgo biloba
Indeloxazine
Nefazodone
Opioids (e.g., desmetramadol , methadone , pethidine (meperidine) , tapentadol , tramadol , levorphanol )
SERT Tooltip Serotonin transporter (SRIs Tooltip Serotonin reuptake inhibitors )
Others: A-80426
Amoxapine
Antihistamines (e.g., brompheniramine , chlorphenamine , dimenhydrinate , diphenhydramine , mepyramine (pyrilamine) , pheniramine , tripelennamine )
Antipsychotics (e.g., loxapine , ziprasidone )
Arylcyclohexylamines (e.g., 3-MeO-PCP , esketamine , ketamine , methoxetamine , phencyclidine )
Cyclobenzaprine
Delucemine
Dextromethorphan
Dextrorphan
Efavirenz
Hypidone
Medifoxamine
Mesembrine
Mifepristone
MIN-117 (WF-516)
N-Me-5-HT
Opioids (e.g., dextropropoxyphene , methadone , pethidine (meperidine) , levorphanol , tapentadol , tramadol )
Roxindole
VMATs Tooltip Vesicular monoamine transporters Others
5-HT1
5-HT1A
Agonists: 8-OH-DPAT
Adatanserin
Amphetamine
Antidepressants (e.g., etoperidone , hydroxynefazodone , nefazodone , trazodone , triazoledione , vilazodone , vortioxetine )
Atypical antipsychotics (e.g., aripiprazole , asenapine , brexpiprazole , cariprazine , clozapine , lurasidone , quetiapine , ziprasidone )
Azapirones (e.g., buspirone , eptapirone , gepirone , perospirone , tandospirone )
Bay R 1531
Befiradol
BMY-14802
Cannabidiol
Dimemebfe
Dopamine
Ebalzotan
Eltoprazine
Enciprazine
Ergolines (e.g., bromocriptine , cabergoline , dihydroergotamine , ergotamine , lisuride , LSD , methylergometrine (methylergonovine) , methysergide , pergolide )
F-11,461
F-12826
F-13714
F-14679
F-15063
F-15,599
Flesinoxan
Flibanserin
Flumexadol
Hypidone
Lesopitron
LY-293284
LY-301317
mCPP
MKC-242
Naluzotan
NBUMP
Osemozotan
Oxaflozane
Pardoprunox
Piclozotan
Rauwolscine
Repinotan
Roxindole
RU-24,969
S-14,506
S-14671
S-15535
Sarizotan
Serotonin (5-HT)
SSR-181507
Sunepitron
Tryptamines (e.g., 5-CT , 5-MeO-DMT , 5-MT , bufotenin , DMT , indorenate , N-Me-5-HT , psilocin , psilocybin )
TGBA01AD
U-92,016-A
Urapidil
Vilazodone
Xaliproden
Yohimbine
Antagonists: Atypical antipsychotics (e.g., iloperidone , risperidone , sertindole )
AV965
Beta blockers (e.g., alprenolol , carteolol , cyanopindolol , iodocyanopindolol , isamoltane , oxprenolol , penbutolol , pindobind , pindolol , propranolol , tertatolol )
BMY-7,378
CSP-2503
Dotarizine
Ergolines (e.g., metergoline )
FCE-24379
Flopropione
GR-46611
Isamoltane
Lecozotan
Mefway
Metitepine (methiothepin)
MIN-117 (WF-516)
MPPF
NAN-190
Robalzotan
S-15535
SB-649,915
SDZ 216-525
Spiperone
Spiramide
Spiroxatrine
UH-301
WAY-100135
WAY-100635
Xylamidine
5-HT1B
Agonists: Anpirtoline
CGS-12066A
CP-93129
CP-94253
CP-122,288
CP-135807
Eltoprazine
Ergolines (e.g., bromocriptine , dihydroergotamine , ergotamine , methylergometrine (methylergonovine) , methysergide , pergolide )
mCPP
RU-24,969
Serotonin (5-HT)
Triptans (e.g., avitriptan , donitriptan , eletriptan , sumatriptan , zolmitriptan )
TFMPP
Tryptamines (e.g., 5-BT , 5-CT , 5-MT , DMT )
Vortioxetine
5-HT1D
Agonists: CP-122,288
CP-135807
CP-286601
Ergolines (e.g., bromocriptine , cabergoline , dihydroergotamine , ergotamine , LSD , methysergide )
GR-46611
L-694247
L-772405
mCPP
PNU-109291
PNU-142633
Serotonin (5-HT)
TGBA01AD
Triptans (e.g., almotriptan , avitriptan , donitriptan , eletriptan , frovatriptan , naratriptan , rizatriptan , sumatriptan , zolmitriptan )
Tryptamines (e.g., 5-BT , 5-CT , 5-Et-DMT , 5-MT , 5-(nonyloxy)tryptamine , DMT )
5-HT1E
5-HT1F
5-HT2
5-HT2A
Agonists: 25H/NB series (e.g., 25I-NBF , 25I-NBMD , 25I-NBOH , 25I-NBOMe , 25B-NBOMe , 25C-NBOMe , 25TFM-NBOMe , 2CBCB-NBOMe , 25CN-NBOH , 2CBFly-NBOMe )
2Cs (e.g., 2C-B , 2C-E , 2C-I , 2C-T-2 , 2C-T-7 , 2C-T-21 )
2C-B-FLY
2CB-Ind
5-Methoxytryptamines (5-MeO-DET , 5-MeO-DiPT , 5-MeO-DMT , 5-MeO-DPT , 5-MT )
α-Alkyltryptamines (e.g., 5-Cl-αMT , 5-Fl-αMT , 5-MeO-αET , 5-MeO-αMT , α-Me-5-HT , αET , αMT )
AL-34662
AL-37350A
Bromo-DragonFLY
Dimemebfe
DMBMPP
DOx (e.g., DOB , DOC , DOI , DOM )
Efavirenz
Ergolines (e.g., 1P-LSD , ALD-52 , bromocriptine , cabergoline , ergine (LSA) , ergometrine (ergonovine) , ergotamine , lisuride , LA-SS-Az , LSB , LSD , LSD-Pip , LSH , LSP , methylergometrine (methylergonovine) , pergolide )
Flumexadol
IHCH-7113
Jimscaline
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
O-4310
Oxaflozane
PHA-57378
PNU-22394
PNU-181731
RH-34
SCHEMBL5334361
Phenethylamines (e.g., lophophine , mescaline )
Piperazines (e.g., BZP , quipazine , TFMPP )
Serotonin (5-HT)
TCB-2
TFMFly
Tryptamines (e.g., 5-BT , 5-CT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Antagonists: 5-I-R91150
5-MeO-NBpBrT
AC-90179
Adatanserin
Altanserin
Antihistamines (e.g., cyproheptadine , hydroxyzine , ketotifen , perlapine )
AMDA
Atypical antipsychotics (e.g., amperozide , aripiprazole , asenapine , blonanserin , brexpiprazole , carpipramine , clocapramine , clorotepine , clozapine , fluperlapine , gevotroline , iloperidone , lurasidone , melperone , mosapramine , ocaperidone , olanzapine , paliperidone , quetiapine , risperidone , sertindole , zicronapine , ziprasidone , zotepine )
Chlorprothixene
Cinanserin
CSP-2503
Deramciclane
Dotarizine
Eplivanserin
Ergolines (e.g., amesergide , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
Fananserin
Flibanserin
Glemanserin
Irindalone
Ketanserin
KML-010
Landipirdine
LY-393558
mCPP
Medifoxamine
Metitepine (methiothepin)
MIN-117 (WF-516)
Naftidrofuryl
Nantenine
Nelotanserin
Opiranserin (VVZ-149)
Pelanserin
Phenoxybenzamine
Pimavanserin
Pirenperone
Pizotifen
Pruvanserin
Rauwolscine
Ritanserin
Roluperidone
S-14671
Sarpogrelate
Serotonin antagonists and reuptake inhibitors (e.g., etoperidone , hydroxynefazodone , lubazodone , mepiprazole , nefazodone , triazoledione , trazodone )
SR-46349B
TGBA01AD
Teniloxazine
Temanogrel
Tetracyclic antidepressants (e.g., amoxapine , aptazapine , esmirtazapine , maprotiline , mianserin , mirtazapine )
Tricyclic antidepressants (e.g., amitriptyline )
Typical antipsychotics (e.g., chlorpromazine , fluphenazine , haloperidol , loxapine , perphenazine , pimozide , pipamperone , prochlorperazine , setoperone , spiperone , spiramide , thioridazine , thiothixene , trifluoperazine )
Volinanserin
Xylamidine
Yohimbine
5-HT2B
Agonists: 4-Methylaminorex
Aminorex
Amphetamines (e.g., chlorphentermine , cloforex , dexfenfluramine , fenfluramine , levofenfluramine , norfenfluramine )
BW-723C86
DOx (e.g., DOB , DOC , DOI , DOM )
Ergolines (e.g., cabergoline , dihydroergocryptine , dihydroergotamine , ergotamine , methylergometrine (methylergonovine) , methysergide , pergolide )
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
Piperazines (e.g., TFMPP )
PNU-22394
Ro60-0175
Serotonin (5-HT)
Tryptamines (e.g., 5-BT , 5-CT , 5-MT , α-Me-5-HT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Antagonists: Agomelatine
Atypical antipsychotics (e.g., amisulpride , aripiprazole , asenapine , brexpiprazole , cariprazine , clozapine , N-desalkylquetiapine (norquetiapine) , N-desmethylclozapine (norclozapine) , olanzapine , pipamperone , quetiapine , risperidone , ziprasidone )
Cyproheptadine
EGIS-7625
Ergolines (e.g., amesergide , bromocriptine , lisuride , LY-53857 , LY-272015 , mesulergine )
Ketanserin
LY-393558
mCPP
Metadoxine
Metitepine (methiothepin)
Pirenperone
Pizotifen
Propranolol
PRX-08066
Rauwolscine
Ritanserin
RS-127445
Sarpogrelate
SB-200646
SB-204741
SB-206553
SB-215505
SB-221284
SB-228357
SDZ SER-082
Tegaserod
Tetracyclic antidepressants (e.g., amoxapine , mianserin , mirtazapine )
Trazodone
Typical antipsychotics (e.g., chlorpromazine )
TIK-301
Yohimbine
5-HT2C
Agonists: 2Cs (e.g., 2C-B , 2C-E , 2C-I , 2C-T-2 , 2C-T-7 , 2C-T-21 )
5-Methoxytryptamines (5-MeO-DET , 5-MeO-DiPT , 5-MeO-DMT , 5-MeO-DPT , 5-MT )
α-Alkyltryptamines (e.g., 5-Cl-αMT , 5-Fl-αMT , 5-MeO-αET , 5-MeO-αMT , α-Me-5-HT , αET , αMT )
A-372159
AL-38022A
Alstonine
CP-809101
Dimemebfe
DOx (e.g., DOB , DOC , DOI , DOM )
Ergolines (e.g., ALD-52 , cabergoline , dihydroergotamine , ergine (LSA) , ergotamine , lisuride , LA-SS-Az , LSB , LSD , LSD-Pip , LSH , LSP , pergolide )
Flumexadol
Lorcaserin
MDxx (e.g., MDA (tenamfetamine) , MDMA (midomafetamine) , MDOH , MMDA )
MK-212
ORG-12962
ORG-37684
Oxaflozane
PHA-57378
Phenethylamines (e.g., lophophine , mescaline )
Piperazines (e.g., aripiprazole , BZP , mCPP , quipazine , TFMPP )
PNU-22394
PNU-181731
Ro60-0175
Ro60-0213
Serotonin (5-HT)
Tryptamines (e.g., 5-BT , 5-CT , bufotenin , DET , DiPT , DMT , DPT , psilocin , psilocybin , tryptamine )
Vabicaserin
WAY-629
WAY-161503
YM-348
Antagonists: Adatanserin
Agomelatine
Atypical antipsychotics (e.g., asenapine , clorotepine , clozapine , fluperlapine , iloperidone , melperone , olanzapine , paliperidone , quetiapine , risperidone , sertindole , ziprasidone , zotepine )
Captodiame
CEPC
Cinanserin
Cyproheptadine
Deramciclane
Desmetramadol
Dotarizine
Eltoprazine
Ergolines (e.g., amesergide , bromocriptine , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
Etoperidone
Fluoxetine
FR-260010
Irindalone
Ketanserin
Ketotifen
Latrepirdine (dimebolin)
Medifoxamine
Metitepine (methiothepin)
Nefazodone
Pirenperone
Pizotifen
Propranolol
Ritanserin
RS-102221
S-14671
SB-200646
SB-206553
SB-221284
SB-228357
SB-242084
SB-243213
SDZ SER-082
Tedatioxetine
Tetracyclic antidepressants (e.g., amoxapine , aptazapine , esmirtazapine , maprotiline , mianserin , mirtazapine )
TIK-301
Tramadol
Trazodone
Tricyclic antidepressants (e.g., amitriptyline , nortriptyline )
Typical antipsychotics (e.g., chlorpromazine , loxapine , pimozide , pipamperone , thioridazine )
Xylamidine
5-HT3 –7
5-HT3
Agonists: Alcohols (e.g., butanol , ethanol (alcohol) , trichloroethanol )
m-CPBG
Phenylbiguanide
Piperazines (e.g., BZP , mCPP , quipazine )
RS-56812
Serotonin (5-HT)
SR-57227
SR-57227A
Tryptamines (e.g., 2-Me-5-HT , 5-CT , bufotenidine (5-HTQ) )
Volatiles/gases (e.g., halothane , isoflurane , toluene , trichloroethane )
YM-31636
Antagonists: Alosetron
Anpirtoline
Arazasetron
AS-8112
Atypical antipsychotics (e.g., clozapine , olanzapine , quetiapine )
Azasetron
Batanopride
Bemesetron (MDL-72222)
Bupropion
Cilansetron
CSP-2503
Dazopride
Dolasetron
Galanolactone
Granisetron
Hydroxybupropion
Lerisetron
Memantine
Ondansetron
Palonosetron
Ramosetron
Renzapride
Ricasetron
Tedatioxetine
Tetracyclic antidepressants (e.g., amoxapine , mianserin , mirtazapine )
Thujone
Tropanserin
Tropisetron
Typical antipsychotics (e.g., loxapine )
Volatiles/gases (e.g., nitrous oxide , sevoflurane , xenon )
Vortioxetine
Zacopride
Zatosetron
5-HT4
5-HT5A
5-HT6
Agonists: Ergolines (e.g., dihydroergocryptine , dihydroergotamine , ergotamine , lisuride , LSD , mesulergine , metergoline , methysergide )
Hypidone
Serotonin (5-HT)
Tryptamines (e.g., 2-Me-5-HT , 5-BT , 5-CT , 5-MT , Bufotenin , E-6801 , E-6837 , EMD-386088 , EMDT , LY-586713 , N-Me-5-HT , ST-1936 , tryptamine )
WAY-181187
WAY-208466
Antagonists: ABT-354
Atypical antipsychotics (e.g., aripiprazole , asenapine , clorotepine , clozapine , fluperlapine , iloperidone , olanzapine , tiospirone )
AVN-101
AVN-211
AVN-322
AVN-397
BGC20-760
BVT-5182
BVT-74316
Cerlapirdine
EGIS-12,233
GW-742457
Idalopirdine
Ketanserin
Landipirdine
Latrepirdine (dimebolin)
Masupirdine
Metitepine (methiothepin)
MS-245
PRX-07034
Ritanserin
Ro 04-6790
Ro 63-0563
SB-258585
SB-271046
SB-357134
SB-399885
SB-742457
Tetracyclic antidepressants (e.g., amoxapine , mianserin )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , nortriptyline )
Typical antipsychotics (e.g., chlorpromazine , loxapine )
5-HT7
Antagonists: Atypical antipsychotics (e.g., amisulpride , aripiprazole , asenapine , brexpiprazole , clorotepine , clozapine , fluperlapine , olanzapine , risperidone , sertindole , tiospirone , ziprasidone , zotepine )
Butaclamol
DR-4485
EGIS-12,233
Ergolines (e.g., 2-Br-LSD (BOL-148) , amesergide , bromocriptine , cabergoline , dihydroergotamine , ergotamine , LY-53857 , LY-215,840 , mesulergine , metergoline , methysergide , sergolexole )
JNJ-18038683
Ketanserin
LY-215,840
Metitepine (methiothepin)
Ritanserin
SB-258719
SB-258741
SB-269970
SB-656104
SB-656104A
SB-691673
SLV-313
SLV-314
Spiperone
SSR-181507
Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin , mirtazapine )
Tricyclic antidepressants (e.g., amitriptyline , clomipramine , imipramine )
Typical antipsychotics (e.g., acetophenazine , chlorpromazine , chlorprothixene , fluphenazine , loxapine , pimozide )
Vortioxetine