Medication used for major depressive disorder
Gepirone , sold under the brand name Exxua , is a medication used for the treatment of major depressive disorder .[ 1] It is taken orally .[ 1]
Side effects of gepirone include dizziness , nausea , insomnia , abdominal pain , and dyspepsia (indigestion).[ 1] Gepirone acts as a partial agonist of the serotonin 5-HT1A receptor .[ 1] [ 2] An active metabolite of gepirone, 1-(2-pyrimidinyl)piperazine , is an α2 -adrenergic receptor antagonist .[ 1] [ 3] Gepirone is a member of the azapirone group of compounds.[ 2]
Gepirone was synthesized by Bristol-Myers Squibb in 1986 and was developed and marketed by Fabre-Kramer Pharmaceuticals .[ 4] It was approved for the treatment of major depressive disorder in the United States in September 2023.[ 4] This came after the drug had been rejected by the Food and Drug Administration (FDA) three times over two decades due to insufficient evidence of effectiveness.[ 5]
Gepirone is indicated for the treatment of major depressive disorder (MDD) in adults.[ 1] Of 15 clinical trials of gepirone for major depressive disorder submitted to the U.S. Food and Drug Administration (FDA), three were excluded for methodological reasons, three were deemed "failed" and "uninformative", seven were deemed negative and did not demonstrate effectiveness, and two were deemed positive and did show effectiveness.[ 6] Two positive trials are needed for FDA drug approval, with this being the case regardless of the number of negative trials.[ 7] In the two positive trials of gepirone for depression, the drug significantly outperformed placebo in terms of depressive symptom reduction and showed effect sizes similar to those of other approved antidepressants.[ 1] [ 8] In both trials, gepirone reduced depressive symptoms by about 2.5 points more than placebo on the 52-point Hamilton Depression Rating Scale (17-item version or HAMD-17).[ 1] The baseline depression scores in the trials ranged from 22.7 to 24.2 in the different patient groups.[ 1]
Gepirone comes in the form of extended-release tablets of the hydrochloride salt , gepirone hydrochloride, in the strengths 18.2 mg, 36.3 mg, 54.5 mg, and 72.6 mg.[ 1]
Specific populations [ edit ] It is not known if gepirone is safe in women who are breastfeeding. Medications with more data in this setting may be preferred.[ 9]
Gepirone is contraindicated in people that have experienced an allergic reaction to gepirone, a corrected QT interval > 450 msec, a history of congenital long QT syndrome , use medications that strongly inhibit CYP3A4 (an enzyme involved in gepirone's metabolism), severe liver problems, or have used a monoamine oxidase inhibitor (MAOI) medication within 14 days.[ 1]
Serious side effects of gepirone include QT prolongation (increases the risk of a potentially life-threatening cardiac arrhythmia called torsade de pointes ), serotonin syndrome (especially in the presence of other serotonergic drugs), and activation of mania or hypomania in people with bipolar disorder . Common side effects include dizziness , nausea , insomnia , abdominal pain , and dyspepsia (indigestion).[ 1]
The CYP3A4 inhibitors ketoconazole and verapamil strongly increase exposure to gepirone, whereas lithium , paroxetine , and warfarin have no effect on exposure to gepirone.[ 1] The CYP3A4 inducer rifampin profoundly decreases exposure to gepirone.[ 1]
Gepirone acts as a selective partial agonist of the 5-HT1A receptor .[ 2] Unlike its relative buspirone , however, gepirone has greater efficacy in activating the 5-HT1A and has negligible affinity for the D2 receptor (30- to 50-fold lower in comparison to buspirone ).[ 10] However, similarly to buspirone, gepirone metabolizes into 1-(2-pyrimidinyl)piperazine (1-PP), which is known to act as a potent antagonist of the α2 -adrenergic receptor .[ 3]
The absolute bioavailability of gepirone is 14 to 17%.[ 1] The time to peak concentrations of gepirone with the extended-release formulation is 6 hours.[ 1] When taken with a high-fat meal, the time to peak levels decreases to 3 hours.[ 1] A high-fat meal increases exposure to gepirone, with the effect increasing dependent on the amount of fat in the meal.[ 1] Peak concentrations were increased by 27% with a low-fat meal, 55% with a medium-fat meal, and 62% with a high-fat meal, while area-under-the-curve levels of gepirone were increased by 14% with a low-fat meal, 22% with a medium-fat meal, and 32 to 37% with a high-fat meal.[ 1] The effect was similar for the metabolites of gepirone, 1-PP and 3'-hydroxygepirone (3'-OH-gepirone).[ 1]
The apparent volume of distribution of gepirone is approximately 94.5 L.[ 1] The plasma protein binding of gepirone in vitro is 72% and is independent of concentration.[ 1] The plasma protein binding of 3'-OH-gepirone is 59% and of 1-PP is 42%.[ 1]
Gepirone is metabolized primarily by CYP3A4 .[ 1] Its major metabolites are 1-PP and 3'-OH-gepirone, both of which are pharmacologically active .[ 1] These metabolites are present in the circulation at higher concentrations than gepirone.[ 1]
With a single oral dose of radiolabeled gepirone, 81% is recovered in urine and 13% is recovered in feces as metabolites .[ 1] About 60% of the gepirone is eliminated in urine within 24 hours.[ 1]
The terminal half-life of gepirone as the extended-release form is approximately 5 hours.[ 1]
Gepirone is a member of the azapirone group of compounds and is structurally related to buspirone , tandospirone , and other azapirones.[ 11]
Gepirone was developed by Bristol-Myers Squibb in 1986,[ 5] but was out-licensed to Fabre-Kramer in 1993. The FDA rejected approval for gepirone in 2002 and 2004.[ 5] It was submitted for the preregistration (NDA) phase again in May 2007 after adding additional information from clinical trials as the FDA required in 2009. However, in 2012 it once again failed to convince the FDA of its qualities for treating anxiety and depression.[ 5] In December 2015, the FDA once again gave gepirone a negative review for depression due to concerns of efficacy.[ 12] However, in March 2016, the FDA reversed its decision and gave gepirone ER a positive review.[ 13] Gepirone ER was finally approved for the treatment of major depressive disorder in the United States in September 2023.[ 5]
Society and culture [ edit ] The brand name of gepirone is Exxua.[ 1] Former tentative brand names which were never used included Ariza, Variza, and Travivo.[ 4]
Gepirone is under development for the treatment of decreased libido and generalized anxiety disorder (GAD).[ 4] [ 14] [ 15] As of October 2023, it is in phase III clinical trials for these indications.[ 4] The pro-sexual effects of gepirone appear to be independent of its antidepressant and anxiolytic effects.[ 14] [ 15]
^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am "EXXUA (gepirone) extended-release tablets, for oral use" (PDF) . Mission Pharmacal Company . U.S. Food and Drug Administration. 2023. Archived (PDF) from the original on 28 September 2023. Retrieved 28 September 2023 . ^ a b c Kishi T, Meltzer HY, Matsuda Y, Iwata N (August 2014). "Azapirone 5-HT1A receptor partial agonist treatment for major depressive disorder: systematic review and meta-analysis" (PDF) . Psychological Medicine . 44 (11): 2255–2269. doi :10.1017/S0033291713002857 . PMID 24262766 . S2CID 20830020 . Archived from the original (PDF) on 18 February 2019. ^ a b Halbreich U, Montgomery SA (1 November 2008). Pharmacotherapy for Mood, Anxiety, and Cognitive Disorders . American Psychiatric Pub. pp. 375–. ISBN 978-1-58562-821-6 . ^ a b c d e "Gepirone - Fabre-Kramer Pharmaceuticals" . AdisInsight . Springer Nature Switzerland AG. Archived from the original on 11 April 2023. Retrieved 28 September 2023 . ^ a b c d e Becker Z (28 September 2023). "Decades long regulatory odyssey ends with FDA nod for Fabre-Kramer's depression med Exxua" . Fierce Pharma . ^ Firth S (30 November 2015). "Controversial Antidepressant Comes Up for FDA OK -- Again" . MedPage Today . ^ Kirsch I (2014). "Antidepressants and the Placebo Effect" . Zeitschrift für Psychologie . 222 (3): 128–134. doi :10.1027/2151-2604/a000176 . PMC 4172306 . PMID 25279271 . ^ "FDA Rules Favorably On Efficacy Of Travivo (Gepirone ER) For Treatment Of Major Depressive Disorder" . Fabre-Kramer Pharmaceuticals, Inc . Cision PR Newswire. 17 March 2016. ^ "Gepirone" . Drugs and Lactation Database . National Institute of Child Health and Human Development. 2006. PMID 37856644 . Retrieved 11 December 2023 . ^ Schatzberg AF, Nemeroff CB (2009). The American Psychiatric Publishing Textbook of Psychopharmacology . American Psychiatric Pub. pp. 494–. ISBN 978-1-58562-309-9 . ^ Kaur Gill A, Bansal Y, Bhandari R, Kaur S, Kaur J, Singh R, et al. (July 2019). "Gepirone hydrochloride: a novel antidepressant with 5-HT1A agonistic properties". Drugs of Today . 55 (7): 423–437. doi :10.1358/dot.2019.55.7.2958474 . PMID 31347611 . S2CID 198911377 . ^ "Gepirone ER" . Adis Insight. Archived from the original on 6 August 2016. Retrieved 13 January 2016 . ^ "FDA Rules Favorably On Efficacy Of Travivo (Gepirone ER) For Treatment Of Major Depressive Disorder" (Press release). 17 March 2016. Archived from the original on 24 September 2017. Retrieved 23 January 2018 . ^ a b Fabre LF, Brown CS, Smith LC, Derogatis LR (May 2011). "Gepirone-ER treatment of hypoactive sexual desire disorder (HSDD) associated with depression in women". The Journal of Sexual Medicine . 8 (5): 1411–1419. doi :10.1111/j.1743-6109.2011.02216.x . PMID 21324094 . ^ a b Fabre LF, Clayton AH, Smith LC, Goldstein I, Derogatis LR (March 2012). "The effect of gepirone-ER in the treatment of sexual dysfunction in depressed men". The Journal of Sexual Medicine . 9 (3): 821–829. doi :10.1111/j.1743-6109.2011.02624.x . PMID 22240272 .
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
α1
Agonists Antagonists Abanoquil Ajmalicine Alfuzosin Anisodamine Anisodine Atiprosin Atypical antipsychotics (e.g., brexpiprazole , clozapine , olanzapine , quetiapine , risperidone ) Benoxathian Beta blockers (e.g., adimolol , amosulalol , arotinolol , carvedilol , eugenodilol , labetalol ) Buflomedil Bunazosin Corynanthine Dapiprazole Domesticine Doxazosin Ergolines (e.g., acetergamine , ergotamine , dihydroergotamine , lisuride , nicergoline , terguride ) Etoperidone Fenspiride Hydroxyzine Indoramin Ketanserin L-765,314 mCPP Mepiprazole Metazosin Monatepil Moxisylyte Naftopidil Nantenine Neldazosin Niaprazine Niguldipine Pardoprunox Pelanserin Perlapine Phendioxan Phenoxybenzamine Phentolamine Phenylpiperazine antidepressants (e.g., hydroxynefazodone , nefazodone , trazodone , triazoledione ) Piperoxan Prazosin Quinazosin Quinidine Silodosin Spegatrine Spiperone Talipexole Tamsulosin Terazosin Tiodazosin Tolazoline Tetracyclic antidepressants (e.g., amoxapine , maprotiline , mianserin ) Tricyclic antidepressants (e.g., amitriptyline , clomipramine , doxepin , imipramine , trimipramine ) Trimazosin Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine ) Urapidil WB-4101 Zolertine
α2
Agonists Antagonists 1-PP Adimolol Amesergide Aptazapine Atipamezole Atypical antipsychotics (e.g., asenapine , brexpiprazole , clozapine , lurasidone , olanzapine , paliperidone , quetiapine , risperidone , zotepine ) Azapirones (e.g., buspirone , gepirone , ipsapirone , tandospirone ) BRL-44408 Buflomedil Cirazoline Efaroxan Esmirtazapine Fenmetozole Fluparoxan Idazoxan Ketanserin Lisuride mCPP Mianserin Mirtazapine NAN-190 Pardoprunox Phentolamine Phenoxybenzamine Piperoxan Piribedil Rauwolscine Rotigotine Setiptiline Spegatrine Spiroxatrine Sunepitron Terguride Tolazoline Typical antipsychotics (e.g., chlorpromazine , fluphenazine , loxapine , thioridazine ) Yohimbine
β
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