- List of investigational antidepressants
- List of antidepressants
- Lists of drugs
- Lists of investigational drugs
- List of investigational hallucinogens and entactogens
- NV-5138
- Antidepressant
- List of investigational antipsychotics
- Atypical antidepressant
- S-Adenosyl methionine
list of investigational antidepressants
List of investigational antidepressants GudangMovies21 Rebahinxxi LK21
This is a list of investigational antidepressants, or drugs that are currently under development for clinical use in the treatment of depression but are not yet approved. Specific indications include major depressive disorder, treatment-resistant depression, dysthymia, bipolar depression, and postpartum depression, among others.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.
This list was last comprehensively updated in August 2024. It is likely to become outdated with time.
Under development
= Preregistration
=Buprenorphine/samidorphan (ALKS-5461) – μ-opioid receptor partial agonist, κ-opioid receptor antagonist, δ-opioid receptor antagonist, and μ-opioid receptor antagonist combination – New Drug Application (NDA) rejected in 2019, no updates since 2021
= Phase 3
=Aticaprant (AVTX-501; CERC-501; JNJ-3964; JNJ-67953964; LY-2456302) – κ-opioid receptor antagonist
CYB003 (CYB-003; deuterated psilocybin analogue) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen
Cycloserine/lurasidone (Cyclurad; NRX-101) – ionotropic glutamate NMDA receptor glycine site partial agonist and atypical antipsychotic (non-selective monoamine receptor modulator) combination
Esmethadone (dextromethadone; REL-1017) – ionotropic glutamate NMDA receptor antagonist and other actions
Ketamine (HTX-100; NRX-100) – ionotropic glutamate NMDA receptor antagonist
Navacaprant (BTRX-140; BTRX-335140; CYM-53093; NMRA-140; NMRA-335140) – κ-opioid receptor antagonist
Pimavanserin (ACP-103; BVF-048; Nuplazid) – serotonin 5-HT2A receptor antagonist or inverse agonist
Psilocybin (COMP-360) – non-selective serotonin receptor agonist and psychedelic hallucinogen
Seltorexant (JNJ-42847922; JNJ-7922; MIN-202) – orexin OX2 receptor antagonist
SEP-4199 (non-racemic amisulpride; aramisulpride/esamisulpride [85:15 ratio]) – atypical antipsychotic (dopamine D2 and D3 receptor antagonist and serotonin 5-HT2B and 5-HT7 receptor antagonist)
SNG-12 (Synapsinae) – glycine transporter 1 (GlyT1) inhibitor
Solriamfetol (Sunosi; JZP-110; SKLN05; ARL-N05; YKP-10A; R-228060; ADX-N05) – norepinephrine and dopamine reuptake inhibitor and trace amine-associated receptor 1 (TAAR1) agonist
Ulotaront (SEP-363856; SEP-856) – serotonin 5-HT1A receptor agonist and trace amine-associated receptor 1 (TAAR1) agonist
= Phase 2/3
=PRAX-114 – extrasynaptic GABAA receptor-preferring positive allosteric modulator and neurosteroid
= Phase 2
=4-Chlorokynurenine (4-CL-KYN; AV-101) – ionotropic glutamate NMDA receptor glycine site antagonist and kynurenine modulator
Ademetionine (MSI-190; MSI-195; S-Adenosyl-L-Methionine; Sam-E; SAMe; Strada) – cofactor in monoamine neurotransmitter biosynthesis
ALTO-100 (NSI-189) – unknown mechanism of action (hippocampal neurogenesis stimulant and indirect brain-derived neurotrophic factor (BDNF) modulator)
ALTO-203 – histamine H3 receptor agonist
Apimostinel (AGN-241660; GATE-202; NRX-1074) – ionotropic glutamate NMDA receptor glycine site partial agonist
Arketamine ((R)-ketamine; PCN-101) – ionotropic glutamate NMDA receptor antagonist
Azetukalner (1OP-2198; Encukalner; VRX-621698; XEN-1101; XPF-008) – KCNQ potassium channel agonist
BHV-7000 (BPN-25203; KB-3061) – KCNQ2 potassium channel stimulant
BI-1358894 – transient receptor potential cation TRPC4 and TRPC5 channel inhibitor
Blixeprodil (GM-1020; (R)-4-fluorodeschloroketamine ((R)-4-FDCK) – ionotropic glutamate NMDA receptor antagonist
Bretisilocin (GM-2505; 5F-MET; 5-fluoro-N-methyl-N-ethyltryptamine) – serotonin 5-HT2A and 5-HT2C receptor agonist, serotonin 5-HT2B receptor antagonist, psychedelic hallucinogen, and serotonin releasing agent
Brezivaptan (ANC-501; THY-1773; TS-1211; TS-121) – vasopressin V1b receptor antagonist
Centanafadine (CTN; EB-1020) – serotonin, norepinephrine, and dopamine reuptake inhibitor
Deudextromethorphan/quinidine (AVP-786; CTP-786; d-DM/Q; d6-DM/Q; deuterated dextromethorphan/ultra-low-dose quinidine) – sigma σ1 receptor agonist, serotonin reuptake inhibitor, ionotropic glutamate NMDA receptor antagonist, other actions, and CYP2D6 inhibitor combination
Dimethyltryptamine (N,N-Dimethyltryptamine; DMT; N,N-DMT; BMND-01; BMND-02; BMND-03) – non-selective serotonin receptor agonist and psychedelic hallucinogen
Emestedastat (UE-2343; Xanamem) – 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor (glucocorticoid synthesis inhibitor)
Esketamine (CLE-100) – ionotropic glutamate NMDA receptor antagonist
FKB-01MD (FKB01MD; TGBA-01AD; TGBA01AD) – serotonin reuptake inhibitor, serotonin 5-HT1A receptor agonist, serotonin 5-HT1D receptor modulator, and serotonin 5-HT2 receptor agonist
Itruvone (PH-10; PH-10A; PH10-NS) – chemoreceptor cell stimulant, vomeropherine, and neurosteroid
JNJ-54175446 (JNJ-5446) – purinergic P2X7 receptor antagonist
JNJ-55308942 – purinergic P2X7 receptor antagonist
Ketamine (extended-release; R-107; R107) – ionotropic glutamate NMDA receptor antagonist
Ketamine (intranasal; Ereska; PMI-100; PMI-150; SLS-002; TUR-002) – ionotropic glutamate NMDA receptor antagonist
Ketamine (prolonged-release oral; KET-01) – ionotropic glutamate NMDA receptor antagonist
Liafensine (BMS-820836; DB-104) – serotonin, norepinephrine, and dopamine reuptake inhibitor
Lisdexamfetamine (Vyvanse) – norepinephrine and dopamine releasing agent
Lysergic acid diethylamide (LSD; MB-22001) – non-selective serotonin receptor agonist and psychedelic hallucinogen
Mebufotenin (5-MeO-DMT; 5-Methoxy-N,N-Dimethyltryptamine; BPL-002; BPL-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen
Mifepristone (Mifeprex; RU-38486; RU-486) – progesterone receptor antagonist, glucocorticoid receptor antagonist, and androgen receptor antagonist
NBI-1070770 – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
NORA-520 (brexanolone prodrug) – GABAA receptor positive allosteric modulator and neurosteroid
Onabotulinum toxin A (BoNTA; Botox; Botulinum toxin A injectable; GSK-1358820; OnabotA X; onabotulinumtoxinA X; Vistabel; Vistabex) – acetylcholine release inhibitor and neuromuscular blocking agent
Onfasprodil (CAD-9271; MIJ-821; MIJ821) – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
OPC-64005 – serotonin, norepinephrine, and dopamine reuptake inhibitor
Osavampator (TAK-653; NBI-1065845; NBI-845) – ionotropic glutamate AMPA receptor positive allosteric modulator
OSU-6162 (PNU-9639; PNU-96391; PNU-96391A) – serotonin 5-HT2A receptor partial agonist (non-hallucinogenic), dopamine D2 receptor partial agonist, and sigma σ1 receptor ligand (so-called "monoaminergic stabilizer")
PDC-1421 (ABV-1504; ABV-1505; ABV-1601; BLI-1005) – norepinephrine reuptake inhibitor
Pegipanermin (DN-TNF; INB-03; LIVNate; Quellor; XENP-1595; XENP-345; XPro-1595; XPro595; XPro) – tumor necrosis factor α (TNFα) inhibitor
Pramipexole (CTC-413; CTC-501) – dopamine D2, D3, and D4 receptor agonist
Pregnenolone methyl ether (3β-methoxypregnenolone; MAP-4343) – microtubule-associated protein (MAP) stimulant and tubulin polymerization promoter
Ralmitaront (RG-7906; RO-6889450) – trace amine-associated receptor 1 (TAAR1) agonist
RE-104 (FT-104; 4-HO-DiPT/iprocin prodrug) – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen
Rislenemdaz (AVTX-301; CERC-301; MK-0657) – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
Ropanicant (SUVN-911) – α4β2 nicotinic acetylcholine receptor antagonist
SP-624 – sirtuin 6 (SIRT6) stimulant
SPN-820 (NV-5138; SPN-821) – sestrin2 modulator and mammalian target of rapamycin complex 1 (mTORC1) stimulant
Tebideutorexant (JNJ-61393215; JNJ-3215) – orexin OX1 receptor antagonist
Tildacerfont (SPR-001; LY-2371712) – corticotropin releasing factor receptor 1 (CRF1) antagonist
Tramadol (controlled-release; ETS-6103; ETX-6103; Viotra) – μ-opioid receptor agonist, serotonin and norepinephrine reuptake inhibitor, serotonin 5-HT2C receptor antagonist, and other actions
TS-161 – metabotropic glutamate mGlu2 and mGlu3 receptor antagonist
Zelquistinel (AGN-241751; GATE-251) – ionotropic glutamate NMDA receptor partial positive allosteric modulator
= Phase 1/2
=PT-00114 (PT100114) – corticotropin releasing hormone (CRH) inhibitor
= Phase 1
=ABX-002 (LL-340001 prodrug) – thyroid hormone receptor β (TRβ) agonist
Agomelatine (ALTO-300; agomelatine 25 mg formulation) – serotonin 5-HT2C receptor antagonist and melatonin MT1 and MT2 receptor agonist
BI-1569912 – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
BMND07 (BMND-07; dimethyltryptamine or 5-MeO-DMT combination drug) – non-selective serotonin receptor agonist, serotonergic hallucinogen, and other actions combination
BRII-296 (extended-release injectable aqueous suspension formulation of brexanolone) – GABAA receptor positive allosteric modulator and neurosteroid
Brilaroxazine (RP-5000; RP-5063) – atypical antipsychotic (non-selective monoamine receptor modulator)
Carbidopa/oxitriptan (EVX-101) – serotonin precursor (5-hydroxytryptophan; 5-HTP) and aromatic L-amino acid decarboxylase (AAAD) inhibitor combination
Crisdesalazine (AAD-2004) – microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitor
DGX-001 – gut–brain axis modulator
Dimethyltryptamine (N,N-dimethyltryptamine; DMT; N,N-DMT; VLS-01) – non-selective serotonin receptor agonist and psychedelic hallucinogen
DSP-3456 – metabotropic glutamate mGlu2 and mGlu3 receptor negative allosteric modulator
Ebselen (DR-3305; Harmokisane; PZ-51; SPI-1005; SPI-3005) – multiple mechanisms of action
Icalcaprant (CVL-354) – κ-opioid receptor antagonist
KAR-2618 (GFB-887) – transient receptor potential cation TRPC4 and TRPC5 channel inhibitor
PIPE-307 – muscarinic acetylcholine M1 receptor antagonist
SAL-0114 – undefined mechanism of action
Scopolamine (DPI-385-CVS; DPI-386; DPI-386 Nasal Gel; DPI-386-SG; DPI-386-SS; DPI-387; DPI-521-CG; DPI-550-TBI; INSCOP spray) – non-selective muscarinic acetylcholine receptor antagonist
Traneurocin (NA-831; Cycloprolylglycine; CPG) – unknown or undefined / ionotropic glutamate AMPA receptor positive allosteric modulator, GABAA receptor positive allosteric modulator, and racetam-like drug
XW-10508 (oral esketamine conjugate prodrug) – ionotropic glutamate NMDA receptor antagonist
Zalsupindole (DLX-001; DLX-1; AAZ; AAZ-A-154) – non-hallucinogenic serotonin 5-HT2A receptor agonist
= Preclinical
=2-Bromo-LSD (bromolysergide; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions
ACD856 (ACD-856) – tropomyosin receptor kinase TrkA, TrkB, and TrkC positive allosteric modulator
AKO-003 (ketamine-based psychedelic formulation; ketamine/specific plant bioactive) – ionotropic glutamate NMDA receptor antagonist, dissociative hallucinogen, and "specific plant bioactive" combination
ALTO-202 – NR2B subunit-containing ionotropic glutamate NMDA receptor antagonist
Brexpiprazole (long-acting injectable; MTD-211) – atypical antipsychotic (non-selective monoamine receptor modulator)
CB-03 (CB-04; CB-003; CB03-154) – KCNQ2 and KCNQ3 potassium channel stimulant
CRHR1 antagonist therapeutic (HMNC Brain Health) – corticotropin releasing factor receptor 1 (CRF1) antagonist
Duloxetine (oral suspension) – serotonin and norepinephrine reuptake inhibitor
EB-003 – non-hallucinogenic serotonin receptor agonist and psychoplastogen
EGX-A – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen
EGX-B – serotonin 5-HT2A receptor agonist and psychedelic hallucinogen
ENX-104 – presynaptic dopamine D2 and D3 autoreceptor antagonist (at low doses)
ENX-105 – dopamine D2 and D3 receptor antagonist and serotonin 5-HT1A and 5-HT2A receptor agonist (non-hallucinogenic)
Etifoxine deuterated (GRX-917) – GABAA receptor positive allosteric modulator and translocator protein (TSPO; peripheral benzodiazepine receptor) agonist (neurosteroidogenesis stimulant)
GABA positive allosteric modulator (CS Bay Therapeutics) – GABAA receptor positive allosteric modulator
INV-88 – macrophage migration inhibitory factor (MIF) inhibitor
ITI-333 – serotonin 5-HT2A receptor antagonist, μ-opioid receptor biased partial agonist, α1A-adrenergic receptor antagonist, and dopamine D1 receptor antagonist
ITI-1549 – non-hallucinogenic serotonin 5-HT2A receptor agonist and serotonin 5-HT2B receptor antagonist
Ketamine (depot; ALA-3000) – ionotropic glutamate NMDA receptor antagonist
Lithium cocrystal (AL-001; LiProSal; lithium salicylate L-proline ionic cocrystal) – unknown mechanism of action and mood stabilizer (improved formulation of lithium)
LPH-5 – selective serotonin 5-HT2A receptor partial agonist and psychedelic hallucinogen
LPCN-1154 (LPCN1154; oral brexanolone) – GABAA receptor positive allosteric modulator and neurosteroid
Lucid-PSYCH (Lucid-201) – undefined mechanism of action and psychedelic hallucinogen
Mebufotenin (5-MeO-DMT; 5-methoxy-N,N-dimethyltryptamine; LSR-1019) – non-selective serotonin receptor agonist and psychedelic hallucinogen
Midomafetamine (microneedle transdermal patch; 3,4-methylenedioxymethamphetamine; MDMA) – serotonin, norepinephrine, and dopamine releasing agent and weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist (entactogen and weak psychedelic hallucinogen)
Nezavist – GABAA receptor positive allosteric modulator
NLX-101 (F-15599) – serotonin 5-HT1A receptor full agonist
PSIL-001 (DMT analogue) – serotonin 5-HT1 receptor modulator (non-hallucinogenic)
PSIL-002 (DMT analogue) – serotonin 5-HT1 receptor modulator (non-hallucinogenic)
PSYLO-3001 (Psylo-3001) – non-hallucinogenic non-selective serotonin receptor agonist and psychoplastogen
PSYLO-4001 (Psylo-4001) – non-hallucinogenic serotonin 5-HT2A receptor agonist and psychoplastogen
SYT-510 – endocannabinoid reuptake inhibitor
TF-0066 – undefined mechanism of action
= Research
=BHV-5000 – low-trapping ionotropic glutamate NMDA receptor antagonist
NP-10679 – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
Psilocybin (MYCO-001; MYCO-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen
PSYLO-5001 (Psylo-5001) – non-hallucinogenic serotonin 5-HT2A receptor agonist and psychoplastogen
Small molecule therapeutic - Rugen Therapeutics – undefined mechanism of action
= Phase unknown
=Amuxetine – serotonin, norepinephrine, and dopamine reuptake inhibitor
EDG-005 – undefined mechanism of action
EDG-006 – undefined mechanism of action
Iloperidone (Fanapt; Fanaptum; Fiapta; HP-873; ILO-522; VYV-683; Zomaril) – atypical antipsychotic (non-selective monoamine receptor modulator)
INV-407 – undefined mechanism of action
Ketamine (intravenous/oral; Braxia) – ionotropic glutamate NMDA receptor antagonist
SK-2110 (buprenorphine implant) – μ-opioid receptor partial agonist, κ-opioid receptor antagonist, and δ-opioid receptor antagonist – under development in China
Venlafaxine (controlled-release) – serotonin and norepinephrine reuptake inhibitor
Not under development
= Development suspended
=BVF-045 (bupropion/undisclosed serotonin reuptake inhibitor) – norepinephrine and dopamine reuptake inhibitor, nicotinic acetylcholine receptor negative allosteric modulator, and serotonin reuptake inhibitor combination
Dexmedetomidine (BXCL-501; Igalmi; KalmPen) – α2-adrenergic receptor agonist
ETX-155 – GABAA receptor positive allosteric modulator
Ganaxolone (CCD-1042; Ztalmy) – GABAA receptor positive allosteric modulator and neurosteroid
= No development reported
=AAG-561 – corticotropin releasing hormone (CRH) inhibitor
Adinazolam (Deracyn; U-41123; U-41123F) – GABAA receptor positive allosteric modulator and benzodiazepine
Amitifadine (DOV-21947; EB-1010) – serotonin, norepinephrine, and dopamine reuptake inhibitor
AN-788 (NSD-788) – serotonin and dopamine reuptake inhibitor
ANAVEX 1-41 (blarcamesine analogue) – sigma σ1 receptor agonist, muscarinic acetylcholine receptor modulator, and sodium and chloride channel modulator
Aripiprazole (transdermal; AQS-1301) – atypical antipsychotic (non-selective monoamine receptor modulator)
Arketamine (HR-071603; (R)-ketamine nasal spray) – ionotropic glutamate NMDA receptor antagonist
AZD-8108 – ionotropic glutamate NMDA receptor antagonist
BCI-632 – metabotropic glutamate mGlu2 and mGlu3 receptor antagonist
BCI-838 – metabotropic glutamate mGlu2 and mGlu3 receptor antagonist
BMS-866949 (CSTI-500) – serotonin, norepinephrine, and dopamine reuptake inhibitor
BNC-210 (IW-2143) – α7 nicotinic acetylcholine receptor negative allosteric modulator
Bryostatin 1 (MW-904) – protein kinase C (PKC) stimulant
BTRX-246040 (LY-2940094) – nociceptin receptor antagonist
Bupropion/naltrexone (Contrave) – norepinephrine and dopamine reuptake inhibitor, nicotinic acetylcholine receptor negative allosteric modulator, and μ-opioid receptor antagonist combination
Cericlamine (JO-1017) – serotonin reuptake inhibitor
Citalopram/pipamperone (PipCit; PNB-01) – serotonin reuptake inhibitor and typical antipsychotic combination
Depression therapy - Genopia Biomedical – undefined mechanism of action
(R)-Desmethylsibutramine ((+)-desmethylsibutramine; or (R)-desmethylsibutramine/(+)-didesmethylsibutramine) – serotonin, norepinephrine, and dopamine reuptake inhibitor
Deulumateperone (ITI-1284; lumateperone deuterated) – atypical antipsychotic (non-selective monoamine receptor modulator)
Dipraglurant (ADX-48621; mGluR5-NAM) – metabotropic glutamate mGlu5 receptor negative allosteric modulator
Erteberel (LY-500307; SERBA-1) – estrogen receptor β (ERβ) agonist
Esketamine (esketamine DPI; Falkieri; PG061; S-ketamine) – ionotropic glutamate NMDA receptor antagonist
Eszopiclone (Lunesta) – GABAA receptor positive allosteric modulator and Z-drug
EVT-101 (ENS-101) – NR2B subunit-containing ionotropic glutamate NMDA receptor negative allosteric modulator
Fananserin (RP-62203) – serotonin 5-HT2A receptor antagonist and dopamine D4 receptor antagonist
Fibroblast growth factor 1 (FGF-1) – fibroblast growth factor receptor (FGFR) agonist
Filorexant (MK-6096) – orexin OX1 and OX2 receptor antagonist
GEA-857 (alaproclate analogue) – potassium conductance putative blocker
GSK-588045 – serotonin 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonist
GSK-1360707 – serotonin, norepinephrine, and dopamine reuptake inhibitor
HS-10353 – GABAA receptor positive allosteric modulator
Hypidone – serotonin reuptake inhibitor and serotonin 5-HT1A and 5-HT6 receptor agonist
Igmesine (CI-1019; JO-1784) – sigma σ1 receptor agonist
Imiloxan (RS-21361) – α2-adrenergic receptor antagonist
IN-ASTR-001 – undefined mechanism of action
Ketamine (transdermal patch; SHX-001) – ionotropic glutamate NMDA receptor antagonist
Ketamine (sublingual; ketamine wafer; SLS-003; Wafermine) – ionotropic glutamate NMDA receptor antagonist
KFM-19 – adenosine A1 receptor antagonist
LSM-6 (3-hydroxy-N,N-dimethylphenethylamine) – undefined mechanism of action (adrenergic and serotonergic agent; constituent of Limacia scanden Lour.) – was under development in Malaysia
Midomafetamine (3,4-methylenedioxymethamphetamine; MDMA; ecstasy) – serotonin, norepinephrine, and dopamine releasing agent and weak serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonist (entactogen and weak psychedelic hallucinogen)
Mitizodone (HEC-113995) – serotonin reuptake inhibitor and serotonin 5-HT1A and 5-HT1B receptor partial agonist
Nivacortol (nivazole; NEBO-174; novozola) – glucocorticoid receptor antagonist
Omiloxetine – serotonin reuptake inhibitor
Oxitriptan (5-hydroxytryptophan; 5-HTP; EVX-301) – serotonin precursor
Pseudohypericin – undefined mechanism of action (constituent of St John's wort)
Psilocybin (CYB-001; INT0052/2020) – non-selective serotonin receptor agonist and psychedelic hallucinogen
Psilocybin (biosynthetic psilocybin; PB-1818) – non-selective serotonin receptor agonist and psychedelic hallucinogen
QRX-002 – ionotropic glutamate NMDA receptor antagonist
RG-7351 – trace amine-associated receptor 1 (TAAR1) agonist
Riluzole (sublingual; BHV-0223; Nurtec) – complex mechanism of action or glutamatergic modulator
Risperidone (Risperdal) – atypical antipsychotic (non-selective monoamine receptor modulator)
SAR-102779 (SAR-10279) – neurokinin NK2 receptor antagonist
SD-254 (deuterated venlafaxine) – serotonin and norepinephrine reuptake inhibitor
SEP-378614 – undefined mechanism of action
SNA-1 – undefined mechanism of action
SPL-801-B ((2R,6R)-hydroxynorketamine; 6-HNK) – non-hallucinogenic ketamine derivative/metabolite
TrkB receptor antagonist (Celon Pharma) – tropomyosin receptor kinase TrkB antagonist
YDP-2225 – undefined mechanism of action
= Development discontinued
=ABT-436 – vasopressin V1b receptor antagonist
Adatanserin (WAY-SEB-324; WY-50324; SEB-324) – serotonin 5-HT1A receptor partial agonist and serotonin 5-HT2A and 5-HT2C receptor antagonist
ADX-71149 (JNJ-1813; JNJ-40411813; JNJ-mGluR2-PAM) – metabotropic glutamate mGlu2 receptor modulator
Amesergide (LY-237733) – serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor antagonist, α2-adrenergic receptor antagonist, and other actions
Amibegron (SR-58611; SR-58611A) – β3-adrenergic receptor agonist
Aprepitant (MK-869) – neurokinin NK1 receptor antagonist
ARA-014418 (AR-A014418; GSK-3β Inhibitor VIII) – glycogen synthase kinase GSK-3β inhibitor
Armodafinil (CEP-10953; Nuvigil; (R)-modafinil) – atypical dopamine reuptake inhibitor
Atipamezole (antisedan; MPV-1248) – α2-adrenergic receptor antagonist
Atomoxetine (LY-139603; Strattera; Tomoxetine) – norepinephrine reuptake inhibitor
AZD-2066 – metabotropic glutamate mGlu5 receptor antagonist
AZD-2327 – δ-opioid receptor agonist
AZD-7268 – δ-opioid receptor agonist
AZD-8129 (AR-A000002; AR-A2XX; AR-A2) – serotonin 5-HT1B receptor antagonist
Basimglurant (NOE-101; RG-7090; RO-4917523) – metabotropic glutamate mGlu5 receptor antagonist
Befloxatone (MD-370503) – monoamine oxidase MAO-A reversible inhibitor
BMS-181101 (BMY-42569) – serotonin reuptake inhibitor and serotonin 5-HT1A and 5-HT1D receptor agonist
Buspirone (transdermal; BuSpar Patch) – serotonin 5-HT1A receptor partial agonist
Casopitant (GW-679769; GW679769) – neurokinin NK1 receptor antagonist
Centpropazine – unknown mechanism of action
Cibinetide (ARA-290) – erythropoietin receptor (EpoR) agonist
Citalopram (controlled-release) – serotonin reuptake inhibitor
Clavulanic acid (RX-10100; Serdaxin; Zoraxel) – β-lactamase inhibitor and unknown mechanism of action (glutamate transporter GLT1 expression enhancer, dopamine, glutamate, and serotonin modulator, possibly via Munc18-1 and Rab4 interactions)
Clovoxamine (DU-23811) – serotonin and norepinephrine reuptake inhibitor
Coluracetam (BCI-540; MKC-231) – ionotropic glutamate AMPA receptor positive allosteric modulator, choline uptake and acetylcholine synthesis enhancer, and racetam
CP-316311 – corticotropin releasing hormone (CRH) inhibitor
Crinecerfont (NBI-74788; SSR-125543; SSR-125543A) – corticotropin releasing factor receptor 1 (CRF1) antagonist
CRL-41789 – undefined mechanism of action
Cutamesine (AGY-94806; Msc-1; SA-4503) – sigma σ1 receptor agonist
CX157 (KP157; TriRima; Tyrima) – monoamine oxidase MAO-A reversible inhibitor
Dapoxetine (LY-210448; Priligy) – serotonin reuptake inhibitor
Dasotraline (DSP-225289; SEP-225289; SEP-0225289; SEP-289) – serotonin, norepinephrine, and dopamine reuptake inhibitor
DDP-225 – norepinephrine reuptake inhibitor and serotonin 5-HT3 receptor antagonist
Decoglurant – metabotropic glutamate mGlu2 and mGlu3 receptor antagonist
Delequamine (RS-15385; RS-15385197) – α2-adrenergic receptor antagonist
Delucemine (NPS-1506) – ionotropic glutamate NMDA receptor polyamine site antagonist and serotonin reuptake inhibitor
Dexmecamylamine (AT-5214; NIH-11008; S-mecamylamine; TC-5214) – α3β4 and α4β2 nicotinic acetylcholine receptor negative allosteric modulator
Dexnafenodone (LU-43706) – serotonin and norepinephrine reuptake inhibitor
DMP-695 – corticotropin releasing hormone (CRH) inhibitor
DOV-216303 – serotonin, norepinephrine, and dopamine reuptake inhibitor
DPC-368 – undefined mechanism of action
DSP-1200 – serotonin 5-HT2A receptor antagonist, dopamine D2 receptor antagonist, and α2A-adrenergic receptor antagonist
Edivoxetine (EDP-125; LY-2216684) – norepinephrine reuptake inhbitor
Elzasonan (CP-448187) – serotonin 5-HT1B and 5-HT1D receptor antagonist
Emapunil (AC-5216; XBD-173) – translocator protein (TSPO; peripheral benzodiazepine receptor) agonist (neurosteroidogenesis stimulant)
Emicerfont (GW-876008; GW-876008X) – corticotropin releasing factor receptor 1 (CRF1) antagonist
Eplivanserin (Ciltyri; Sliwens; SR-46349; SR-46349B; SR-46615A) – serotonin 5-HT2A receptor antagonist
Eptapirone (F-11440) – serotonin 5-HT1A receptor full agonist
Esreboxetine ((S,S)-Reboxetine; AXS-14; PNU-165442G) – norepinephrine reuptake inhibitor
Esuprone (LU-43839) – monoamine oxidase MAO-A reversible inhibitor
Ethyl eicosapentaenoic acid (Ethyl-EPA) – omega-3 fatty acid
Farampator (CX-691; ORG-24448) – ionotropic glutamate AMPA receptor positive allosteric modulator
Fasoracetam (AEVI-001; LAM-105; MDGN-001; NFC-1; NS-105) – unknown mechanism of action (metabotropic glutamate receptor modulator) and racetam
FCE-25876 – serotonin reuptake inhibitor
Flerobuterol (CRL-40827) – β-adrenergic receptor agonist
Flesinoxan (DU-29373) – serotonin 5-HT1A receptor agonist
Flibanserin (Addyi; BIMT-17; Girosa) – serotonin 5-HT1A receptor agonist, serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor antagonist, and dopamine D4 receptor antagonist
(R)-Fluoxetine – serotonin reuptake inhibitor
Fluparoxan (GR-50360; GR-50360A) – α2-adrenergic receptor antagonist
Gaboxadol (LU-02030; LU-2-030; MK-0928; OV-101; THIP) – GABAA receptor agonist
Girisopam (EGIS-5810; GYKI-51189) – GABAA receptor positive allosteric modulator and benzodiazepine
GYKI-52895 – dopamine reuptake inhibitor
Haloperidol (CLR-3001) – typical antipsychotic (non-selective monoamine receptor modulator; low-dose withdrawal therapy)
HT-2157 (SNAP-37889) – galanin GAL3 receptor antagonist
ICI-170809 (ZM-170809) – serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor antagonist
Idazoxan – α2-adrenergic receptor antagonist
Ipsapirone (BAY-Q-7821; TVX-Q-7821) – serotonin 5-HT1A receptor partial agonist
IRFI-165 – adenosine A1 receptor antagonist
Istradefylline (KW-6002; Nourianz; Nouriast) – adenosine A2 receptor antagonist
JNJ-18038683 – serotonin 5-HT7 receptor antagonist
JNJ-19567470 (CRA-5626; R-317573) – corticotropin releasing factor receptor 1 (CRF1) antagonist
JNJ-26489112 – unknown mechanism of action (topiramate successor)
JNJ-39393406 – α7 nicotinic acetylcholine receptor positive allosteric modulator
Lanicemine (AZD-6765) – low-trapping ionotropic glutamate NMDA receptor antagonist
LB-100 (LB-1) – protein phosphatase 2A (PP2A) inhibitor
Levoprotiline (CGP-12103; CGP-12103A; CGS-12103; R(–)-oxaprotiline; R(–)-hydroxymaprotiline) – histamine H1 receptor antagonist, other actions, and tetracyclic antidepressant
Lithium – unknown mechanism of action and mood stabilizer
Litoxetine (IXA-001; SL-810385) – serotonin reuptake inhibitor and weak serotonin 5-HT3 receptor antagonist
Losmapimod (FTX-1821; GS-856553; GSK-856553; GW-856553; GW-856553X) – p38-α/β mitogen-activated protein kinase (MAPK) inhibitor and double homeobox 4 (DUX4) inhibitor
LU-AA34893 (LU-AA-34893) – serotonin receptor modulator
LU-AA39959 (LU-AA-39959) – ion channel modulator
Lubazodone (SM-50C; YM-35992; YM-992) – serotonin reuptake inhibitor and serotonin 5-HT2A receptor antagonist
Masitinib (AB-07105; AB-1010; Alsitek; Masican; Masipro; Masiviera) – tyrosine kinase inhibitor and other actions
Mecamylamine (Inversine; Tridmac) – nicotinic acetylcholine receptor negative allosteric modulator
MIN-117 (WF-516) – serotonin and dopamine reuptake inhibitor, serotonin 5-HT1A and 5-HT7 receptor antagonist, and α1-adrenergic receptor antagonist
MK-1942 – undefined mechanism of action
ML-105 – undefined mechanism of action
Naloxone/tianeptine (TNX-601; TNX-601-CR; TNX-601-ER) – weak and atypical μ- and δ-opioid receptor agonist, other actions, tricyclic antidepressant, and μ-opioid receptor antagonist combination
Naluzotan (PRX-00023) – serotonin 5-HT1A receptor partial agonist and sigma σ1 receptor antagonist
NB-415 – vasopressin V1b receptor antagonist
Neboglamine (nebostinel; CR-2249; XY-2401) – ionotropic glutamate NMDA receptor glycine site positive allosteric modulator
Nefiracetam (BRN 6848330; CCRIS 6729; DM 9384; DMPPA; DN-9384; DZL-221; HL-0812; HPI-001; Motiva; Translon) – unknown mechanism of action (voltage-gated calcium channel potentiator, α4β2 nicotinic acetylcholine receptor potentiator, ionotropic glutamate NMDA receptor potentiator (possible glycine site partial positive allosteric modulator), ionotropic glutamate AMPA receptor potentiator, and GABAA receptor agonist) and racetam
Nemifitide (INN-00835) – unknown mechanism of action
NS-2359 (GSK-372475) – serotonin, norepinephrine, and dopamine reuptake inhibitor
NS-2389 (GW-650250; GW-650250A) – serotonin, norepinephrine, and dopamine reuptake inhibitor
ORM-10921 – α2C-adrenergic receptor antagonist
Orvepitant (GW-823296; GW-823296X; GW823296) – neurokinin NK1 receptor antagonist
Osanetant (ACER-801; SR-142801; SR-142806) – neurokinin NK3 receptor antagonist
Pexacerfont (BMS-562086) – corticotropin releasing factor receptor 1 (CRF1) antagonist
PF-04455242 – κ-opioid receptor antagonist
PT-150 (ORG-34517; SCH-900636) – glucocorticoid receptor antagonist and androgen receptor antagonist
Radafaxine (GW-353162; (2S,3S)-hydroxybupropion) – norepinephrine and dopamine reuptake inhibitor
Ramelteon (Rozerem; TAK-375) – melatonin MT1 and MT2 receptor agonist
Rapastinel (BV-102; GLYX-13; TPPT-amide) – ionotropic glutamate NMDA receptor glycine site partial agonist
RG-7166 – serotonin, norepinephrine, and dopamine reuptake inhibitor
Ritanserin (R-55667) – serotonin 5-HT2A and 5-HT2C receptor antagonist
Robalzotan (AZD-7371; NAD-299) – serotonin 5-HT1A receptor antagonist
Rolipram (ME-3167; ZK-62711) – phosphodiesterase 4 (PDE4) inhibitor
Sabcomeline (BCI-224; CEB-242; Memric; SB-202026) – muscarinic acetylcholine M1 receptor agonist
Saredutant (SR-48968) – neurokinin NK2 receptor antagonist
SB-236057 – serotonin 5-HT1B receptor inverse agonist
SB-245570 – serotonin 5-HT1B receptor antagonist
Sibutramine (Aoquqing; BTS-54524; Ectiva; KES-524; Meridia; Reductase; Reductil; Reduxade; Sibutral) – serotonin, norepinephrine, and dopamine reuptake inhibitor
Siramesine (LU-28179) – sigma σ2 receptor agonist
Sirukumab (CNTO-136; Plivensia) – interleukin 6 (IL-6) inhibitor
SKL-10406 (SKL-DEP) – serotonin, norepinephrine, and dopamine reuptake inhibitor
SKL-PSY (FZ-016) – serotonin 5-HT1A receptor agonist
Sodium phenylbutyrate (slow-release; LU-901; Lunaphen) – histone deacetylase (HDAC) inhibitor
SSR-149415 (SR-149415) – vasopressin V1b receptor antagonist
SSR-241586 – neurokinin NK2 and NK3 receptor antagonist
Tandospirone (metanopirone; Sediel; SM-3997) – serotonin 5-HT1A receptor partial agonist and α2-adrenergic receptor antagonist
Tasimelteon (BMS-214778; Hetlioz; VEC-162) – melatonin MT1 and MT2 receptor agonist
Tedatioxetine (LU-AA24530) – serotonin, norepinephrine, and dopamine reuptake inhibitor, serotonin 5-HT2A, 5-HT2C, and 5-HT3 receptor antagonist, and α1A-adrenergic receptor antagonist
Tianeptine (JNJ-39823277; TPI-1062) – weak and atypical μ- and δ-opioid receptor agonist, other actions, and tricyclic antidepressant
TS-111 – undefined mechanism of action
Tulrampator (CX-1632; S-47445) – ionotropic glutamate AMPA receptor positive allosteric modulator
Vanoxerine (boxeprazine; GBR-12909) – atypical dopamine reuptake inhibitor
Verucerfont (GSK-561679; NBI-77860) – corticotropin releasing factor receptor 1 (CRF1) antagonist
Vestipitant (GW-597599; GW-597599B) – neurokinin NK1 receptor antagonist
Viloxazine (Qelbree) – norepinephrine reuptake inhibitor
VN-2222 – serotonin reuptake inhibitor and serotonin 5-HT1A receptor partial agonist
VUFB-17649 – serotonin reuptake inhibitor
VUFB-18285 – serotonin reuptake inhibitor
ZD-4974 – neurokinin NK1 receptor antagonist
Zelatriazin (TAK-041; NBI-1065846; NBI-846) – G protein-coupled receptor 139 (GPR139) agonist
Ziprasidone (Geodon) – atypical antipsychotic (non-selective monoamine receptor modulator)
= Preregistration submission withdrawal
=Aripiprazole/sertraline (ASC-01) – atypical antipsychotic (non-selective monoamine receptor modulator) and serotonin reuptake inhibitor combination
= Formal development never or not yet started
=Mevidalen (LY-3154207; D1 PAM) – dopamine D1 receptor positive allosteric modulator – under development for Lewy body disease
Nitrous oxide (N2O; "laughing gas") – ionotropic glutamate NMDA receptor antagonist – being studied for depression but doesn't seem to be being formally developed towards approval
Clinically used drugs
= Approved drugs
=Agomelatine (Valdoxan) – serotonin 5-HT2C receptor antagonist and melatonin MT1 and MT2 receptor agonist
Amineptine (Survector, Maneon) – norepinephrine and dopamine reuptake inhibitor – withdrawn
Amisulpride (Solian) – atypical antipsychotic (dopamine D2 and D3 receptor antagonist and serotonin 5-HT2B and 5-HT7 receptor antagonist)
Amitriptyline (Elavil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Amoxapine (Asendin) – tetracyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Aripiprazole (Abilify) – atypical antipsychotic (non-selective monoamine receptor modulator)
Brexanolone (allopregnanolone; SAGE-547; SGE-102; Zulresso) – GABAA receptor positive allosteric modulator and neurosteroid – approved for postpartum depression
Brexpiprazole (Rexulti) – atypical antipsychotic (non-selective monoamine receptor modulator)
Bupropion (Wellbutrin) – norepinephrine and dopamine reuptake inhibitor and nicotinic acetylcholine receptor negative allosteric modulator
Bupropion/dextromethorphan (Auvelity) – sigma σ1 receptor agonist, serotonin reuptake inhibitor, norepinephrine and dopamine reuptake inhibitor, nicotinic acetylcholine receptor negative allosteric modulator, ionotropic glutamate NMDA receptor antagonist, other actions, and CYP2D6 inhibitor combination
Butriptyline (Evadyne) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator) – discontinued
Cariprazine (Vraylar) – atypical antipsychotic (non-selective monoamine receptor modulator)
Citalopram (Celexa) – serotonin reuptake inhibitor
Desipramine (Norpramin) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Desvenlafaxine (Pristiq) – serotonin and norepinephrine reuptake inhibitor
Desvenlafaxine (extended-release; Khedezla) – serotonin and norepinephrine reuptake inhibitor – withdrawn
Desvenlafaxine (extended-release; WIP-DF17) – serotonin and norepinephrine reuptake inhibitor – registered in South Korea
Dosulepin (dothiepin; Prothiaden) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Doxepin (Sinequan) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Duloxetine (Cymbalta; Drizalma Sprinkle) – serotonin and norepinephrine reuptake inhibitor
Escitalopram (Lexapro) – serotonin reuptake inhibitor
Esketamine (Spravato) – ionotropic glutamate NMDA receptor antagonist
Fluoxetine (Prozac; Sarafem) – serotonin reuptake inhibitor
Fluvoxamine (Luvox) – serotonin reuptake inhibitor
Gepirone (Exxua) – serotonin 5-HT1A receptor partial agonist and α2-adrenergic receptor antagonist
Hypericum extract (LI-160; St John's wort) – undefined mechanism of action
Imipramine (Tofranil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Iproniazid (Marsilid) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor – withdrawn
Isocarboxazid (Marplan) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor
Levomilnacipran (Fetzima) – serotonin and norepinephrine reuptake inhibitor
Levosulpiride (L-sulpiride; Levobren; Levopraid; Levosulpride; RV-12309; Sulpepta) – dopamine D2 and D3 receptor antagonist and serotonin 5-HT4 receptor agonist
Lofepramine (Lomont) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Lumateperone (Caplyta) – atypical antipsychotic (non-selective monoamine receptor modulator)
Lurasidone (Latuda) – atypical antipsychotic (non-selective monoamine receptor modulator)
Maprotiline (Ludiomil) – tetracyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Mianserin (Tolvon) – tetracyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Milnacipran (Dalcipran; Ixel; Savella) – serotonin and norepinephrine reuptake inhibitor
Mirtazapine (Remeron) – α2-adrenergic receptor antagonist, serotonin 5-HT2A, 5-HT2C, and 5-HT3 receptor antagonist, histamine H1 receptor inverse agonist, and tetracyclic antidepressant
Moclobemide (Aurorix; Manerix) – monoamine oxidase MAO-A reversible inhibitor
Nefazodone (BMY-13754; Dutonin; MJ-13754; MS-13754; Nefadar; Serzone) – serotonin 5-HT1A receptor ligand, serotonin 5-HT2A and 5-HT2C receptor antagonist, α1- and α2-adrenergic receptor antagonist, weak serotonin, norepinephrine, and dopamine reuptake inhibitor, and other actions – mostly withdrawn
Nomifensine (Merital; Alival) – norepinephrine and dopamine reuptake inhibitor – withdrawn
Nortriptyline (Aventyl) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Olanzapine (Zyprexa) – atypical antipsychotic (non-selective monoamine receptor modulator)
Olanzapine/fluoxetine (OFC; Symbyax; ZypZac) – atypical antipsychotic (non-selective monoamine receptor modulator) and serotonin reuptake inhibitor combination
Opipramol (Ensidon; G-33040; Insidon; Nisidana) – sigma σ1 and σ2 receptor agonist, serotonin 5-HT2A receptor antagonist, dopamine D2 receptor antagonist, α1-adrenergic receptor antagonist, histamine H1 receptor antagonist, other actions, and tricyclic antidepressant
Paroxetine (Paxil; Seroxat) – serotonin reuptake inhibitor
Phenelzine (Nardil) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor
Protriptyline (Vivactil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Quetiapine (Seroquel) – atypical antipsychotic (non-selective monoamine receptor modulator)
Reboxetine (Edronax) – norepinephrine reuptake inhibitor
Selegiline (Emsam) – monoamine oxidase MAO-B irreversible inhibitor, catecholaminergic activity enhancer, and weak norepineprhine releasing agent (via metabolites)
Sertraline (Zoloft; Lustral) – serotonin reuptake inhibitor
Setiptiline (Tecipul; Tesolon) – serotonin receptor antagonist, α2-adrenergic receptor antagonist, norepinephrine reuptake inhibitor, and tetracyclic antidepressant
Tianeptine (Coaxil; Stablon; Tatinol) – weak and atypical μ- and δ-opioid receptor agonist, other actions, and tricyclic antidepressant
Toludesvenlafaxine (ansofaxine; 4-methylbenzoate desvenlafaxine; desvenlafaxine prodrug; LPM-570065; LY-03005; Ruoxinlin) – serotonin, norepinephrine, and dopamine reuptake inhibitor
Tranylcypromine (Parnate) – monoamine oxidase MAO-A and MAO-B irreversible inhibitor
Trazodone (Oleptro; Trittico) – serotonin 5-HT1A receptor partial agonist, serotonin 5-HT2A and 5-HT2C receptor antagonist, α1- and α2-adrenergic receptor antagonist, weak serotonin reuptake inhibitor, and other actions
Trimipramine (Surmontil) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and/or receptor modulator)
Venlafaxine (Effexor) – serotonin and norepinephrine reuptake inhibitor
Vilazodone (Viibryd) – serotonin reuptake inhibitor and serotonin 5-HT1A receptor agonist
Viloxazine (Vivalan) – norepinephrine reuptake inhibitor
Vortioxetine (Trintellix) – serotonin reuptake inhibitor, serotonin 5-HT1A and 5-HT1B receptor agonist, and serotonin 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist
Zimelidine (Zelmid) – serotonin reuptake inhibitor – withdrawn
Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABAA receptor positive allosteric modulator and neurosteroid – approved for postpartum depression
See also
List of antidepressants
List of investigational drugs
References
Further reading
External links
AdisInsight - Springer