List of investigational headache and migraine drugs

This is a list of investigational headache and migraine drugs, or drugs that are currently under development for clinical use in the treatment of headaches and/or migraines but are not yet approved. They may also be referred to as investigational antimigraine agents.

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 – Indication [Reference]".

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 It is likely to become outdated with time.

Under development

Phase 3

  • Botulinum toxin A (AboBoNT-A; AbobotulinumtoxinA; Alluzience; Azzalure; BoNT-A; BTX-A; Dysport; Reloxin) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine [1]
  • Botulinum toxin A (Bocouture; Incobotulinum toxin A; NT-201; Vibe/Xeomin; ViXe; Xeomeen; Xeomin; Zeomaine) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine [2]
  • Eptinezumab (ALD-403; Lu-AG09221; Vyepti) – monoclonal antibody against calcitonin gene-related peptide (CGRP) – cluster headache [3]
  • Naproxen/rizatriptan (rizatriptan/naproxen) – combination of naproxen (COX inhibitor/NSAID) and rizatriptan (triptan) – migraine [4]
  • Promethazine/sumatriptan (CL-H1T) – combination of promethazine (anthistamine, anticholinergic, other actions) and sumatriptan (triptan) – migraine [5]

Phase 2/3

  • Acetaminophen/naltrexone – combination of acetaminophen (analgesic) and naltrexone (opioid receptor antagonist) – migraine [6]

Phase 2

  • AGX-201 (histamine dihydrochloride salt) – histamine H1 receptor antagonist and histamine H3 receptor agonist – migraine [7][1][2]
  • BHV-2100 – transient receptor potential cation channel subfamily M member 3 (TRPM3) antagonist – migraine [8]
  • Botulinum toxin A longer acting (IPN-10200; mrBoNT) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine [9]
  • CAM-01 (C-AM-01) – undefined mechanism of action – migraine [10]
  • Dihydroergotamine mesilate (DFN-19) – non-selective monoamine receptor modulator and ergoline – migraine [11]
  • Doxepin intranasal (Dolorac) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and receptor modulator and other actions) – headache [12]
  • Elismetrep (K-304; MT-8554) – transient receptor potential cation channel subfamily M member 8 (TRPM8) antagonist – migraine [13]
  • Erenumab (Aimovig; AMG-334) – monoclonal antibody against calcitonin gene-related peptide receptor (CGRPR) – headache [14]
  • Eslicarbazepine acetate (Aptiom; BIA 2-093; ESL; Exalief; SEP-0002093; SEP-2093; Stedesa; Zebinix) – sodium channel blocker – migraine [15]
  • IONIS-PKKRx (ISIS-546254; ISIS-PKKRx) – antisense oligonucleotide against kallikrein – migraine [16]
  • Ketoprofen topical (ELS-M11; Topofen) – COX inhibitor/NSAID – migraine [17]
  • LAT-8881 (AOD9604; Tyr-hGH171191) – human growth hormone protein fragment and lanthionine synthetase C-like protein (LanCL) ligand – migraine [18]
  • LU-AG09222 (ALD-1910) – monoclonal antibody against pituitary adenylate cyclase-activating polypeptide (PACAP) – migraine [19]
  • LY-3451838 (PACAP-38 antibody) – monoclonal antibody against pituitary adenylate cyclase-activating polypeptide (PACAP) – migraine [20]
  • Lysergic acid diethylamide (LSD; MM-120) – non-selective serotonin receptor agonist and psychedelic hallucinogen – cluster headache [21]
  • MTX-101 – undefined mechanism of action – migraine [22]
  • Pasireotide (Signifor; SOM-230) – somatostatin receptor agonist – cluster headache [23]
  • Prabotulinumtoxin A (ABP-450; DWP-450; Evosyal; Jeuveau; Nabota; Nuceiva) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine [24]
  • Sepranolone (isoallopregnanolone; UC-1010) – GABAA receptor negative allosteric modulator and neurosteroid – menstrual migraine [25]
  • TRV-250 – δ-opioid receptor (DOR) agonist – migraine [26]
  • (R)-Verapamil – calcium channel blocker and other actions – cluster headache [27]
  • Zelminemab (AMG-301) – monoclonal antibody against pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R) – migraine [28]

Phase 1/2

  • XC-101 (XC101; XC101-D13H) – serotonin 5-HT1B and 5-HT7 receptor agonist, serotonin 5-HT1D and 5-HT1F receptor partial agonist, and serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor antagonist – migraine [29]

Phase 1

  • 2-Bromo-LSD (bromolysergide; BOL-148; NYPRG-101) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions – cluster headache, migraine[3][4][5]
  • JS-010 – monoclonal antibody against calcitonin gene-related peptide (CGRP) – migraine [30]
  • Meloxicam – COX inhibitor/NSAID – migraine [31]

Preclinical

  • 2-Bromo-LSD (bromolysergide; BOL-148; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT2A receptor agonist and other actions – cluster headache [6][7][8]
  • GA-2601 – undefined mechanism of action – migraine [32]
  • MST-02 – undefined mechanism of action – migraine [33]
  • TACT908 – serotonin 5-HT1B receptor agonist and non-hallucinogenic serotonin 5-HT2A receptor partial agonist – cluster headache [5][9][10]

Research

  • Research programme: Neurological disorder therapeutics - Lario Therapeutics – undefined mechanism of action – migraine [34]

Phase unknown

Not under development

Preregistration submission withdrawal

  • Frovatriptan (Allegro; Auradol; EN-3266; Frova; Isimig; Migard; Pitunal; Rilamig; SB-209509; SB-209509AX; VML-251) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – menstrual migraine [38]

Suspended

  • Zolmitriptan transdermal (M-207; Qtrypta; triptan microneedle patch) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – cluster headache, migraine [39]

No development reported

  • AF-130 – purinergic P2X3 receptor antagonist – migraine [40]
  • B-244 (AOB-101; AOB-102; AOB-103; AOB-201; AOB-202; AOB-203; B244; nitrosomonas eutropha D23) – bacteria replacement – migraine [41]
  • Carabersat (SB-204269) – undefined mechanism of action (anticonvulsant) – migraine [42]
  • CLE-500 – undefined mechanism of action – cluster headache [43]
  • CT-044 analogues - CERSCI Therapeutics – reactive oxygen species (ROS) inhibitor – migraine [44]
  • Cyclobenzaprine extended release (Amrix; Bonelax; EUR-1002) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and receptor modulator and other actions) – migraine [45]
  • Donepezil (Allydone; Aricept; E-2020; E-2022; Eranz) – acetylcholinesterase inhibitor – migraine [46]
  • Donitriptan mesilate (F-12640) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [47]
  • Estetrol (E4; Donesta) – estrogen (estrogen receptor agonist) – migraine [48]
  • Filorexant (MK-6096) – orexin OX1 and OX2 receptor antagonist – migraine [49]
  • Flunarizine (XEN-007) – calcium channel blocker, non-selective monoamine receptor modulator, other actions – migraine [50]
  • Ibudilast (AV-411; Eyevinal; Ibinal; KC-404; Ketas; MN-166; Pinatos) – phosphodiesterase PDE4 inhibitor – headache [51]
  • IPX-232 – undefined mechanism of action – migraine [52]
  • Ketamine hydrochloride intranasal – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – cluster headache [53]
  • Ondansetron/rizatriptan oral transmucosal film (rizatriptan/ondansetron; MSRX-202) – combination of ondansetron (serotonin 5-HT3 receptor antagonist and antiemetic) and rizatriptan (triptan) [54]
  • Oxytocin (TI-001; TI-114; TNX-1900; TNX-2900) – oxytocin receptor agonist – headache [55]
  • Piroxicam betadex (β-cyclodextrin piroxicam; Brexecam; Brexidol; Brexin; Brexine; Brexinil; CHF 1194; Cicladol; Cycladol; Flogene; piroxicam β-cyclodextrin) – COX inhibitor/NSAID – migraine, tension-type headache [56]
  • Psilocybin (low-dose psilocybin; BPL-PSILO) – non-selective serotonin receptor agonist and psychedelic hallucinogen – headache [57]
  • Psilocybin (MYCO-001; MYCO-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen – headache [58]
  • Psilocybin (SYNP-101; synthetic psilocybin) – non-selective serotonin receptor agonist and psychedelic hallucinogen – cluster headache, migraine [59]
  • Relutrigine (PRAX-562) – sodium channel blocker – headache [60]
  • Research programme: calcitonin gene-related peptide receptor antagonists - Merck (CGRP receptor antagonists; Imidazoazepanes; MK-2918; MK-8825) – calcitonin gene-related peptide receptor (CGRPR) antagonists [61]
  • Research programme: GPCR modulators - Nxera Pharma – various actions [62]
  • Research programme: migraine and pain therapeutics - NeurAxon – various actions – migraine [63]
  • Research programme: pain and migraine therapy - OptiNose (OPT-1005) – undefined mechanism of action – migraine [64]
  • Rizatriptan intranasal – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [65]
  • Rizatriptan oral film – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [66]
  • Salubrin (PH80; PH-80; ORG-39479) – vomeropherine – migraine [67] [68]
  • Sumatriptan (Imigran Nasal Spray; Imitrex Nasal Spray) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – menstrual migraine [69]
  • Sumatriptan transmucosal (Omexa) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [70]
  • Zucapsaicin (cis-capsaicin; Civamide; Civanex; Dolorac; Neuroderm; Zuacta) – transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist – cluster headache, migraine [71]

Discontinued

  • Alniditan (R-91274) – serotonin 5-HT1B and 5-HT1D receptor agonist – migraine [72]
  • Avitriptan (BMS-180048) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [73]
  • Bezisterim (HE-3286; NE-3107; Triolex; 17α-ethynyl-5-androstene-3β,7β,17β-triol) – undefined mechanism of action (synthetic androstenetriol analogue and anti-inflammatory) – migraine [74]
  • BI-44370 (BI44370) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [75]
  • Botulinum toxin A topical (RT-001) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine [76]
  • Carisbamate (Comfyde; JNJ-10234094; RWJ-333369; YKP-509) – unknown mechanism of action – migraine [77][11]
  • Dasolampanel (NGX-426) – ionotropic glutamate AMPA and kainate receptor antagonist – migraine [78]
  • Dextromethorphan/quinidine (DXM/Q; AVP-923; Neurodex; Nuedexta; Zenvia) – combination of dextromethorphan (various actions) and quinidine (various actions) – migraine [79]
  • Dihydroergocryptine (SRN-001) – non-selective monoamine receptor modulator and ergoline – migraine [80]
  • Donitriptan (F-11356) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [81]
  • Dotarizine (Dotaricin; FI-6026) – calcium channel blocker and serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptor antagonist – migraine [82]
  • Dronabinol (Δ9-THC; Δ9-tetrahydrocannabinol; Deltanyne; Elevat; Marinol) – cannabinoid CB1 and CB2 receptor agonist – migraine [83]
  • Ergotamine inhalation (Tempo-ergotamine) – non-selective monoamine receptor modulator and ergoline – migraine [84]
  • Esprolol – beta blocker (β-adrenergic receptor antagonist) – migraine [85]
  • Ethinylestradiol/levonorgestrel (DP3; DR-103; DR-105; LoSeasonique; Seasonique) – combination of ethinylestradiol (an estrogen) and levonorgestrel (a progestogen) and a combined oral contraceptive – menstrual migraine [86]
  • (S)-Ethylisothiouronium diethylphosphate (Difetur; MTR-104; MTR-105; MTR-106; MTR-107; MTR-108; Raviclust; Ravimig; Raviten) – nitric oxide synthase (NOS) inhibitor [87]
  • Fremanezumab (Ajovy; LBR-101; PF-04427429; PF-4427429; RN-307; TEV-48125) – monoclonal antibody against calcitonin gene-related peptide (CGRP) – cluster headache, headache [88]
  • Gabapentin (CI-945; Gabapen; GOE-3450; Neurontin) – gabapentinoid (α2δ subunit-containing voltage-gated calcium channel ligand) – migraine [89]
  • Gabapentin enacarbil (1838262; ASP8825; GSK-1838262; Horizant; Regnite; Solzira; XP13512) – gabapentinoid (α2δ subunit-containing voltage-gated calcium channel ligand) – migraine [90]
  • Ganaxolone (CCD-1042; Ztalmy) – GABAA receptor positive allosteric modulator and neurosteroid – migraine [91]
  • HTL-0022562 (BHV-3100; HTL-22562) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [92]
  • IS-159 – serotonin 5-HT1B and 5-HT1D receptor agonist – migraine [93]
  • Lacosamide (ADD-234037; Erlosamide; Harkoseride; SPM-927; SPM-929; Vimpat; Vimpato) – various actions – migraine [94]
  • Lanepitant (LY-303870) – neurokinin NK1 receptor antagonist – migraine [95]
  • Lidocaine transdermal patch (ADL-87223; LidoPAIN) – sodium channel blocker – headache [96]
  • Lornoxicam (Bosporon; Chlortenoxicam; HN-10000; RO-139297; Safem; TS-110; Xefo) – COX inhibitor/NSAID – migraine [97]
  • LY-2300559 – metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator and cysteinyl leukotriene receptor 1 (CysLTR1) antagonist – migraine [98][12]
  • LY-334370 – serotonin 5-HT1F receptor agonist and triptan – migraine [99]
  • MEDI-0618 – monoclonal antibody against protease-activated receptor 2 (PAR2) – migraine [100]
  • Olcegepant (BIBN-4096; BIBN-4096BS) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [101]
  • Oxytocin (TI-001; TI-114; TNX-1900; TNX-2900) – oxytocin receptor agonist – migraine [102]
  • Perampanel (E-2007; ER-155055-90; Fycompa) – AMPA receptor antagonist – migraine [103]
  • PF-5180999 (PF-05180999) – phosphodiesterase PDE2 inhibitor – migraine [104]
  • PNU-142633 (PNU-142633F) – serotonin 5-HT1D receptor agonist – cluster headache, headache, migraine [105]
  • Prochlorperazine inhalation (AZ-001) – typical antipsychotic (non-selective monoamine receptor modulator) – migraine [106]
  • Propisergide (ergalgin) – serotonin receptor modulator and ergoline – migraine
  • Propofol phosphate (Neuprox; propofol prodrug) – GABAA receptor positive allosteric modulator (propofol prodrug) – migraine [107]
  • Research programme: migraine therapy - Orexo (OX-40; OX641) – undefined mechanism of action – migraine [108]
  • Selurampanel (BGG-492; BGG-492A) – ionotropic glutamate AMPA and kainate receptor antagonist – migraine [109]
  • Sergolexole (LY-281067) – serotonin 5-HT2 receptor antagonist and ergoline – migraine [110]
  • Telcagepant (MK-0974) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [111]
  • Tezampanel (LY-293558; NGX-424; PRN-001-01) – ionotropic glutamate AMPA and kainate receptor antagonist – migraine [112]
  • Tizanidine (AN-021A; AN-021; DS-103282; Sirdalud; Ternelin; Zanaflex) – α2-adrenergic receptor agonist – migraine [113]
  • Tonabersat (SB-220453; USL-260; Xiflam) – connexin 43 (GJA1) inhibitor – migraine [114]
  • Zolmitriptan inhalation (CVT-427) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [115]
  • Zonisamide (AD-810; CI-912; Excegran; Kinaplase; PD-110843; Tremode; Trerief; Zonegran) – calcium channel blocker, sodium channel blocker, and other actions – migraine [116]

Clinically used drugs

Approved drugs

COX inhibitors/NSAIDs

  • Celecoxib (DFN-15; Elyxyb) – COX inhibitor/NSAID – migraine [117]
  • Dexibuprofen (Daxfen; DexOptifen; Movone; (S)-(+)-ibuprofen; Seractil; Ultraprofen) – COX inhibitor/NSAID – headache [118]

Triptans (serotonin 5-HT1B and 5-HT1D receptor agonists)

  • Almotriptan (Almogran; Axert; LAS-31416) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [119]
  • Eletriptan (Relert; Relpax; UK-116044) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine, menstrual migraine [120]
  • Frovatriptan (Allegro; Auradol; EN-3266; Frova; Isimig; Migard; Pitunal; Rilamig; SB-209509; SB-209509AX; VML-251) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [121]
  • Naratriptan (Amerge; GR-85548; GR-85548A; Naramig; SMP-948) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [122]
  • Rizatriptan (L-705126; Maxalt; MK-0462; MK-462) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [123]
  • Rizatriptan oral film (INT-0008; RHB-103; Rizafilm; VersaFilm; RizaPort) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [124]
  • Sumatriptan (Imigran Nasal Spray; Imitrex Nasal Spray) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [125]
  • Zolmitriptan (311-C90; 311C; AscoTop; BW-311C90; Zomig; Zomigon) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – cluster headache, menstrual migraine, migraine [126]
  • Zolmitriptan oral dispersible film (zolmitriptan ODF; Zolmitriptan PharmaFilm; Zolmitriptan RapidFilm; Zolmitriptan Renantos Schmelzfilm) – serotonin 5-HT1B and 5-HT1D receptor agonist and triptan – migraine [127]

Ergolines (non-selective monoamine receptor modulators)

  • Atogepant (AGN-241689; Aquipta; MK-8031; Qulipta) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [131]
  • Eptinezumab (ALD-403; Lu-AG09221; Vyepti) – monoclonal antibody against calcitonin gene-related peptide (CGRP) – migraine [132]
  • Erenumab (Aimovig; AMG-334) – monoclonal antibody against calcitonin gene-related peptide receptor (CGRPR) – migraine [133]
  • Fremanezumab (Ajovy; LBR-101; PF-04427429; PF-4427429; RN-307; TEV-48125) – monoclonal antibody against calcitonin gene-related peptide (CGRP) – migraine [134]
  • Galcanezumab (Emgality; LY-2951742) – monoclonal antibody against calcitonin gene-related peptide (CGRP) – cluster headache, migraine [135]
  • Rimegepant (BHV-3000; BMS-927711; Nurtec; Vydura) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [136]
  • Ubrogepant (MK-1602; Ubrelvy) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [137]
  • Zavegepant (BHV-3500; BMS-742413; PF-07930207; Vazegepant; Zavzpret) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine [138]

Combination drugs

Other drugs

  • Alpiropride (Revistel, Rivistel, Rivestel) – dopamine D2 receptor antagonist – migraine
  • Dimetotiazine (Banistyl, Normelin) – non-selective monoamine receptor modulator – migraine
  • Flumedroxone acetate (Demigran, Leomigran) – progestogen (progesterone receptor agonist) – migraine[13][14]
  • Iprazochrome (Divascan) – serotonin receptor antagonist – migraine
  • Lasmiditan (COL-144; LY-573144; Rayvow; Reyvow) – serotonin 5-HT1F receptor agonist – migraine [141]
  • Lomerizine (DE-090; KB-2796; Migsis) – non-selective monoamine receptor modulator, other actions – migraine [142]
  • Onabotulinum toxin A (BoNTA; Botox; GSK-1358820; OnabotA X; Vistabel; Vistabex) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine [143]
  • Oxetorone (Nocertone, Oxedix) – non-selective monoamine receptor modulator – migraine
  • Topiramate (Epitomax; KW-6485; MCN-4853; RWJ-17021; Topamax; Topimax; Topina) – various actions – migraine [144]
  • Topiramate oral (Eprontia; ET-101) – various actions – migraine [145]
  • Topiramate extended-release (SPN-538; TPM XR; Trokendi XR; Trokesa) – various actions – migraine [146]
  • Valproate semisodium (Depakote; Divalproex; Divalproex sodium; Epival; LA40220) – various actions – migraine [147]

Off-label drugs

See also

References

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