List of investigational anxiety disorder drugs

This is a list of investigational anxiety disorder drugs, or drugs that are currently under development for clinical use in the treatment of anxiety disorders (type unspecified) but are not yet approved.

Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action [Reference]".

This list was last comprehensively updated in September 2025. It is likely to become outdated with time.

Under development

Phase 3

  • Lysergic acid diethylamide (LSD; lysergide; MM-120; MM120) – non-selective serotonin receptor agonist and psychedelic hallucinogen [1][1]
  • Ranquilon (6-phenylhexanoyl)glycyl-L-tryptophan amide; GB-115) – cholecystokinin (CCK) receptor antagonist [2]
  • Soclenicant (BNC-210; BNC210; IW-2143; L-isoleucyl-L-tryptophan) – α7-nicotinic acetylcholine receptor negative allosteric modulator [3]

Phase 2

  • BAER-101 (AZ-7325; AZD-7325) – selective GABAA α2 and α3 subunit-containing receptor positive allosteric modulator and nonbenzodiazepine/cinnoline[2][3][4]
  • Brexanolone caprilcerbate (Glyph Allopregnanolone; GlyphAllo; LYT-300; SPT-300; allopregnanolone prodrug) – GABAA receptor positive allosteric modulator and neurosteroid (brexanolone prodrug) [4]
  • Cannabidiol (CBD; Arvisol) – cannabinoid receptor modulator and other actions [5]
  • Cenobamate (ONO-2017; Ontozry; X-Copri; Xcopri; YKP-3089) – atypical voltage-gated sodium channel blocker and GABAA receptor positive allosteric modulator [6][5]
  • JNJ-42165279 (JNJ-5279) – fatty acid amide hydrolase (FAAH) inhibitor [7]
  • Maritupirdine (CD-008-0045) – serotonin 5-HT6 receptor antagonist [8]
  • Psilocybin low dose (APEX-52) – non-selective serotonin receptor agonist and psychedelic hallucinogen [9]
  • Vortioxetine (Brintellix; Lu-AA21004; trintellix; Vortidif) – serotonin reuptake inhibitor, serotonin 5-HT1A and 5-HT1B receptor agonist, and serotonin 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist [10]
  • Zuranolone (BIIB-125; S-812217; SAGE-217; SGE-797; Zurzuvae) – GABAA receptor positive allosteric modulator and neurosteroid [11]

Phase 1

  • Etifoxine deuterated (deuterated etifoxine; GRX-917) – GABAA receptor positive allosteric modulator, translocator protein (TSPO) agonist, and nonbenzodiazepine/benzoxazine [12]
  • KAR-2618 (GFB-887; TRPC4/5 inhibitor) – transient receptor potential TRPC4 and TRPC5 cation channel inhibitor [13]
  • SNTX-2643 (SENS-01) – atypical serotonin reuptake inhibitor (SRI) (kanna-derived) [14][6]
  • Transient receptor potential channel 4/5 inhibitor - Bristol-Myers Squibb – transient receptor potential TRPC4 and TRPC5 cation channel inhibitor [15]

Preclinical

  • EB-002 (EB-373; psilocin prodrug) – non-selective serotonin receptor agonist and psychedelic hallucinogen [16]
  • Midomafetamine (MDMA; ecstasy) microneedle patch – serotonin–norepinephrine–dopamine releasing agent, weak serotonin 5-HT2 receptor agonist, and entactogen [17]
  • Nerinetide (NA-1; Tat-NR2B9c) – PDZ domain inhibitor [18]
  • OV-4041 – potassium–chloride-cotransporter agonist [19]
  • PSIL-025 – serotonin 5-HT1 receptor modulator [20]

Phase unknown

  • INV-407 – undefined mechanism of action [21]

Not under development

No development reported

  • ACH-36 – undefined mechanism of action [22]
  • Alprazolam sublingual – GABAA receptor positive allosteric modulator and benzodiazepine [23]
  • Antalarmin (CP-154526) – corticotropin-releasing hormone (CRH) inhibitor [24]
  • Buspirone controlled release (Buspirone ER) – serotonin 5-HT1A receptor partial agonist and other actions [25]
  • BW-723C86 – serotonin 5-HT2B and 5-HT2C receptor agonist [26]
  • Cannabidiol dry powder inhalation (RLS-103) – cannabinoid receptor modulator and other actions [27]
  • Darigabat (CVL-865; PF-06372865; PF-6372865) – GABAA receptor positive allosteric modulator [28]
  • Divaplon (RU-32698) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/imidazolpyrimidine [29]
  • Fananserin (RP-62203) – serotonin 5-HT2A receptor antagonist and dopamine D4 receptor antagonist [30]
  • FR260010 (FR-260010) – serotonin 5-HT2C receptor antagonist [31] [32]
  • GSK-588045 (GSK588045) – serotonin 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonist [33]
  • GSK-1360707 – serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) [34]
  • GT-001 – GABAA receptor positive allosteric modulator [35]
  • Guanfacine extended release (Connexyn; Intuniv; Intuniv XR; S-877503; SHP-503; SPD-503) – α2-adrenergic receptor agonist [36]
  • Itriglumide (CR-2945) – cholecystokinin B (CCKB) receptor antagonist [37]
  • Lohocla-201 (Kindolor) – various actions [38]
  • LY-293284 – serotonin 5-HT1A receptor agonist [39]
  • NMRA-511 (BTRX-323511; NMRA-323511) – vasopressin V1A receptor antagonist [40]
  • Paroxetine (Aropax; BRL-29060; Deroxat; Divarius; FG-7051; Frosinor; Motivan; NNC-207051; Paxil; Seroxat; SI-211103; Tagonis) – selective serotonin reuptake inhibitor (SSRI) [41]
  • Psilocybin (MYCO-001; MYCO-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen [42]
  • PT-00114 (PT100114) – corticotropin-releasing hormone (CRH) inhibitor [43]
  • Research programme: allosteric modulators - Addex Therapeutics – various actions [44]
  • Research programme: AMPA receptor agonists - RespireRx (ampakines; CX compounds) – AMPA receptor agonists and brain-derived neurotrophic factor (BDNF) stimulants [45]
  • Research programme: anxiety and neurological disorder therapeutics - AstraZeneca – various actions [46]
  • Research programme: cannabis-based therapeutics - Skye Bioscience – cannabinoid receptor agonists [47]
  • Research programme: neuropeptide S receptor modulators - Pfizer (WYE-198232) – neuropeptide receptor agonists [48]
  • Research programme: oxytocin receptor agonist - Wyeth – oxytocin receptor agonists [49]
  • RGH-618 – metabotropic glutamate mGlu5 receptor negative allosteric modulator [50][7]
  • Riluzole (PK-26124; Rilutek; RP-54274) – various actions [51]
  • Risperidone (JNJ-410397-AAA; R-64766; R064766; Risperdal; Risperdal Consta; Risperdal Depot) – atypical antipsychotic (non-selective monoamine receptor modulator) [52]
  • Saripidem (SL-850274) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/imidazopyridine [53]
  • SB-242084 (SB242084) – serotonin 5-HT2C receptor antagonist [54]
  • SRX-246 (API-246) – vasopressin V1A receptor antagonist [55]
  • SYT-510 – anandamide reuptake inhibitor [56]
  • Tebideutorexant (JNJ-3215; JNJ-61393215; Orexin-1) – orexin OX1 receptor antagonist [57]
  • WAY-100135 – serotonin 5-HT1A receptor antagonist [58]
  • Ziprasidone (CP-88059-01; CP-88059-1; Geodon; ME-2112; RQ-00000003; Zeldox) – atypical antipsychotic (non-selective monoamine receptor modulator) [59]

Discontinued

  • 1-Amino-5-bromouracil (ABU) – undefined mechanism of action [60]
  • ABT-418 – nicotinic acetylcholine receptor agonist [61]
  • ABT-436 – vasopressin V1B receptor antagonist [62]
  • Adipiplon (NG-273) – GABAA receptor positive allosteric modulator and nonbenzodiazepine [63]
  • Alnespirone (S-20499) – serotonin 5-HT1A receptor agonist [64]
  • Alosetron (GR-68755; GR-68755C; Lotronex) – serotonin 5-HT3 receptor antagonist [65]
  • Alpidem (Ananxyl; S-800342-001; SL-800342) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/imidazopyridine [66]
  • Alprazolam lingual spray – GABAA receptor positive allosteric modulator and benzodiazepine [67]
  • AN-788 (IP-2018; NSD788) – serotonin–dopamine reuptake inhibitor (SDRI) [68]
  • AP-521 – serotonin 5-HT1A receptor partial agonist [69]
  • Aprepitant (Emend; L-754030; MK-0869; MK-869; ONO-7436) – neurokinin NK1 receptor antagonist [70]
  • AVN-211 (CD-008-0173) – serotonin 5-HT6 receptor antagonist [71]
  • AVN-397 – undefined mechanism of action [72]
  • AZD-2327 – δ-opioid receptor (DOR) agonist [73]
  • AZD-8129 (AR-A000002; AR-A2XX; AR-A2) – serotonin 5-HT1B receptor antagonist [74]
  • Befloxatone (MD-370503) – reversible inhibitor of monoamine oxidase A (RIMA) [75]
  • Blarcamesine (AE-37; ANA001; ANAVEX 2-73) – sigma σ1 receptor agonist, muscarinic acetylcholine M1 receptor agonist, and ionotropic glutamate NMDA receptor agonist [76]
  • Bretazenil (RO-166028) – GABAA receptor positive allosteric modulator and benzodiazepine [77]
  • Brofaromine (Brofaremine; CGP-11305A; Consonar; Consonev) – reversible inhibitor of monoamine oxidase A (RIMA) and serotonin reuptake inhibitor (SRI) [78]
  • Buspirone transdermal (BuSpar Patch) – serotonin 5-HT1A receptor partial agonist and other actions [79]
  • CGS-12066 – serotonin 5-HT1B receptor partial agonist and other actions [80]
  • Coluracetam (BCI-540; MKC-231) – ionotropic glutamate AMPA receptor positive allosteric modulator, choline uptake and acetylcholine synthesis enhancer, and racetam [81]
  • DAA-1097 – translocator protein (TSPO) agonist [82]
  • Devazepide (Devacade; L-364718; MK-329) – Cholecystokinin A (CCKA) receptor antagonist [83]
  • Dipraglurant (ADX-48621; mGluR5-NAM) – metabotropic glutamate mGlu5 receptor negative allosteric modulator [84]
  • Eglumetad (eglumegad; LY-354740) – metabotropic glutamate mGlu2 and mGlu3 receptor agonist [85]
  • Emapunil (AC-5216; XBD173) – translocator protein (TSPO) agonist [86]
  • Emicerfont (GW-876008; GW876008) – corticotropin releasing factor CRF1 receptor antagonist [87]
  • Enciprazine (D-3112; WY-48624) – serotonin 5-HT1A receptor agonist and α1-adrenergic receptor ligand [88]
  • Eplivanserin (Ciltyri; Sliwens; SR-46349; SR-46349B; SR-46615A) – serotonin 5-HT2A receptor antagonist [89]
  • Eptapirone (F-11440) – serotonin 5-HT1A receptor agonist [90]
  • Esprolol – β-adrenergic receptor antagonist (prodrug of amoxolol) [91][8]
  • Flesinoxan (DU-29373) – serotonin 5-HT1A receptor agonist [92]
  • Gabapentin (CI-945; Gabapen; GOE-3450; Neurontin) – gabapentinoid (α2δ subunit-containing voltage-gated calcium channel ligand) [93]
  • Girisopam (EGIS-5810; GYKI-51189) – GABAA receptor positive allosteric modulator and benzodiazepine [94]
  • GT-2203 – histamine H3 receptor agonist [95]
  • Guanfacine (Guanfacine Carrier Wave project; SPD-554) – α2-adrenergic receptor agonist [96]
  • Ipsapirone (BAY-Q-7821; TVX-Q-7821) – serotonin 5-HT1A receptor partial agonist [97]
  • Isamoltane (CGP-361A) – beta blocker (β-adrenergic receptor antagonist) and serotonin 5-HT1A and 5-HT1B receptor antagonist [98]
  • Itasetron (DAU-6215; U-98079) – serotonin 5-HT3 receptor antagonist [99]
  • ITI-333 – serotonin 5-HT2A receptor antagonist, dopamine D1 receptor antagonist, α1A-adrenergic receptor antagonist, and μ-opioid receptor (MOR) partial agonist [100]
  • JNJ-19567470 (CRA-5626; R-317573) – corticotropin releasing factor CRF1 receptor antagonist [101]
  • Levetiracetam (Keppra; L-059; SIB-S1; UCB-059; UCB-22059; UCB-L059) – synaptic vesicle glycoprotein 2A (SV2A) ligand [102]
  • Lorazepam intranasal – GABAA receptor positive allosteric modulator and benzodiazepine [103]
  • Mavoglurant (AFQ-056; STP-7) – metabotropic glutamate mGlu5 receptor antagonist [104]
  • Midazolam intranasal (ITI-111; midazolam nasal spray; Nayzilam; USL-261) – GABAA receptor positive allosteric modulator and benzodiazepine [105]
  • MK-0777 (L-830982; TPA-023) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/triazolopyridazine [106]
  • NBI-34041 (SB-723620) – corticotropin-releasing hormone (CRH) inhibitor [107]
  • Nerisopam (EGIS-6775; GYKI-52322) – GABAA receptor positive allosteric modulator and benzodiazepine [108]
  • Nivasorexant (ACT-539313; SORA) – orexin OX1 receptor antagonist [109]
  • NS-11821 (NS11821) – GABAA receptor positive allosteric modulator and nonbenzodiazepine [110][3][9]
  • Orvepitant (GW-823296; GW823296X) – neurokinin NK1 receptor antagonist [111]
  • Osanetant (ACER-801; SR-142801; SR-142806) – neurokinin NK3 receptor antagonist [112]
  • Panadiplon (FD-10571; FG-10571; NNC-140571; U-78875) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/pyrazolopyrimidine [113]
  • Pazinaclone (A-77000; DN-2327) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/cyclopyrrolone [114]
  • Pozanicline (A-87089.0; ABT-089) – nicotinic acetylcholine receptor agonist [115]
  • Psilocybin (CYB-001; INT0052/2020) – non-selective serotonin receptor agonist and psychedelic hallucinogen [116]
  • Research programme: depression and anxiety therapies - Roche/Vernalis – undefined mechanism of action [117]
  • Research programme: GPCR modulators - Nxera Pharma – various actions [118]
  • Research programme: monoamine oxidase A inhibitors - CeNeRx BioPharma – monoamine oxidase A (MAO-A) inhibitors [119]
  • Ritanserin (R-55667) – serotonin 5-HT2 receptor antagonist and other actions [120]
  • Robalzotan (AZD-7371; NAD-299) – serotonin 5-HT1A receptor antagonist [121]
  • RS-127445 (MT-500) – serotonin 5-HT2B receptor antagonist [122]
  • SAX-187 (WAY-181187) – serotonin 5-HT6 receptor agonist [123]
  • Sergolexole (LY-281067) – serotonin 5-HT2 receptor antagonist [124]
  • Siramesine (LU-28179) – sigma σ2 receptor agonist [125]
  • SKL-PSY (FZ-016) – serotonin 5-HT1A receptor agonist [126]
  • SSR-241586 (SSR241586) – neurokinin NK2 and NK3 receptor antagonist [127]
  • SUN-8399 – serotonin 5-HT1A receptor agonist [128]
  • Suriclone (RP-31264) – GABAA receptor positive allosteric modulator and nonbenzodiazepine/cyclopyrrolone [129]
  • Talaglumetad (LY-544344) – metabotropic glutamate mGlu2 and mGlu3 receptor agonist (eglumetad prodrug) [130]
  • Tiagabine (A-70569; CEP-6671; Gabitril; NO-050328; NO-328) – GABA transporter 1 (GAT-1) blocker and GABA reuptake inhibitor[10]
  • TMP-301 (Heptares 25; HTL-0014242; HTL14242) – metabotropic glutamate mGlu5 receptor negative allosteric modulator [131]
  • Troriluzole (BHV-4157; Dazluma; FC-4157; trigriluzole) – various actions (riluzole prodrug) [132]
  • Vestipitant (GW-597599) – neurokinin NK1 receptor antagonist [133]
  • Zalospirone (WY-47846) – serotonin 5-HT1A receptor agonist [134]

Clinically used drugs

Approved drugs

  • Emoxypine (ethylmethylhydroxypyridine; Mexidol) – antioxidant and unknown mechanism of action [135]
  • Tandospirone (metanopirone; Sediel; SM-3997) – serotonin 5-HT1A receptor partial agonist [136]
  • Tianeptine (Coaxil; Stablon; Tatinol) – weak atypical μ-opioid receptor agonist and other actions [137]

See also

References

  1. ^ Robison R, Barrow R, Conant C, Foster E, Freedman JM, Jacobsen PL, Jemison J, Karas SM, Karlin DR, Solomon TM, Halperin Wernli M, Fava M (September 2025). "Single Treatment With MM120 (Lysergide) in Generalized Anxiety Disorder: A Randomized Clinical Trial". JAMA. doi:10.1001/jama.2025.13481. PMID 40906494.
  2. ^ "BAER 101". AdisInsight.
  3. ^ a b Maramai S, Benchekroun M, Ward SE, Atack JR (April 2020). "Subtype Selective γ-Aminobutyric Acid Type A Receptor (GABAAR) Modulators Acting at the Benzodiazepine Binding Site: An Update". J Med Chem. 63 (7): 3425–3446. doi:10.1021/acs.jmedchem.9b01312. hdl:11365/1214874. PMID 31738537.
  4. ^ Chen X, Jacobs G, de Kam M, Jaeger J, Lappalainen J, Maruff P, Smith MA, Cross AJ, Cohen A, van Gerven J (December 2014). "The central nervous system effects of the partial GABA-Aα2,3 -selective receptor modulator AZD7325 in comparison with lorazepam in healthy males". Br J Clin Pharmacol. 78 (6): 1298–1314. doi:10.1111/bcp.12413. PMC 4256620. PMID 24802722.
  5. ^ Roberti R, De Caro C, Iannone LF, Zaccara G, Lattanzi S, Russo E (June 2021). "Pharmacology of Cenobamate: Mechanism of Action, Pharmacokinetics, Drug-Drug Interactions and Tolerability". CNS Drugs. 35 (6): 609–618. doi:10.1007/s40263-021-00819-8. PMID 33993416.
  6. ^ Cross, Ryan (19 August 2025). "Exclusive: Sensorium raises $25M to test succulent-derived drug for anxiety". Endpoints News. The company zeroed in on a molecule derived from a South African succulent known to scientists as Sceletium tortuosum and commonly referred to as kanna. [...] the company's drug "was inspired by a unique natural product found among the diverse molecules," but did not confirm if it came from mesembrine. Chewing kanna is linked to rapid calming action within 30 to 60 minutes, [...] Other researchers have previously shown that kanna inhibits the serotonin transporter, an important protein that moves serotonin in and out of the junctions between brain cells. Antidepressants called selective serotonin reuptake inhibitors (SSRIs) also block the serotonin transporter, but typically take four to six weeks for their effects to kick in, creating a puzzle about why the succulent compound worked so quickly. "We were convinced, quite frankly, that it must be hitting some target that we don't know about," Hooker said. "And we went deep. We looked at many hundreds, if not a thousand or more targets." It turned out that the molecule was binding to the serotonin transporter — a bit of a disappointment at first, given the startup's novel mechanism mandate. However, while SSRIs directly block the ability of serotonin to bind to the transporter, Hooker said he was surprised to find that Sensorium's compound binds to a different site on the protein that doesn't compete with serotonin binding. Hooker is writing a paper to describe the mechanism in more detail. The company is also still trying to figure out exactly why touching the transporter differently has such a seemingly rapid action. Early work suggests it is rooted in downstream signaling proteins called kinases that "fundamentally tune the circuit differently," he said. [...] Sensorium has created hundreds of derivatives of the natural molecule to make a version dubbed SNTX-2643, which can be taken orally once a day. Hooker hopes it will provide an alternative to anxiety medications, including SSRIs and benzodiazepines. Hooker declined to say when the Phase 1 study would wrap up.
  7. ^ Galambos J, Domány G, Nógrádi K, Wágner G, Keserű GM, Bobok A, Kolok S, Mikó-Bakk ML, Vastag M, Sághy K, Kóti J, Szakács Z, Béni Z, Gál K, Szombathelyi Z, Greiner I (February 2016). "4-Aryl-3-arylsulfonyl-quinolines as negative allosteric modulators of metabotropic GluR5 receptors: From HTS hit to development candidate". Bioorg Med Chem Lett. 26 (4): 1249–1252. doi:10.1016/j.bmcl.2016.01.024. PMID 26774652.
  8. ^ Matier WL, Patil G (2000). "Esprolol hydrochloride: a new beta adrenergic antagonist with a rapid onset of effect". Heart Dis. 2 (2): 146–150. PMID 11728252.
  9. ^ Zuiker RG, Chen X, Østerberg O, Mirza NR, Muglia P, de Kam M, Klaassen ES, van Gerven JM (March 2016). "NS11821, a partial subtype-selective GABAA agonist, elicits selective effects on the central nervous system in randomized controlled trial with healthy subjects". J Psychopharmacol. 30 (3): 253–262. doi:10.1177/0269881115620435. PMID 26655084.
  10. ^ "Tiagabine". AdisInsight. 24 October 2021. Retrieved 17 January 2026.
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