List of investigational headache and migraine drugs

This is a dynamic list and may never be able to satisfy particular standards for completeness. You can help by editing the page to add missing items, with references to reliable sources.

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 It is likely to become outdated with time.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
• Botulinum toxin A (Bocouture; Incobotulinum toxin A; NT-201; Vibe/Xeomin; ViXe; Xeomeen; Xeomin; Zeomaine) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine
• Eptinezumab (ALD-403; Lu-AG09221; Vyepti) – monoclonal antibody against calcitonin gene-related peptide (CGRP) – cluster headache
• Naproxen/rizatriptan (rizatriptan/naproxen) – combination of naproxen (COX inhibitor/NSAID) and rizatriptan (triptan) – migraine
• Promethazine/sumatriptan (CL-H1T) – combination of promethazine (anthistamine, anticholinergic, other actions) and sumatriptan (triptan) – migraine

Phase 2/3

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

Phase 2

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

Phase 1/2

• XC-101 (XC101; XC101-D13H) – serotonin 5-HT_1B and 5-HT₇ receptor agonist, serotonin 5-HT_1D and 5-HT_1F receptor partial agonist, and serotonin 5-HT_2A, 5-HT_2B, and 5-HT_2C receptor antagonist – migraine

Phase 1

• 2-Bromo-LSD (bromolysergide; BOL-148; NYPRG-101) – non-hallucinogenic serotonin 5-HT_2A receptor agonist and other actions – cluster headache, migraine ^{[3] [4] [5]}
• JS-010 – monoclonal antibody against calcitonin gene-related peptide (CGRP) – migraine
• Meloxicam – COX inhibitor/NSAID – migraine

Preclinical

• 2-Bromo-LSD (bromolysergide; BOL-148; BETR-001, TD-0148A) – non-hallucinogenic serotonin 5-HT_2A receptor agonist and other actions – cluster headache ^{[6] [7] [8]}
• GA-2601 – undefined mechanism of action – migraine
• MST-02 – undefined mechanism of action – migraine
• TACT908 – serotonin 5-HT_1B receptor agonist and non-hallucinogenic serotonin 5-HT_2A receptor partial agonist – cluster headache ^{[5] [9] [10]}

Research

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

Phase unknown

• AST-004 – adenosine A₁ and A₃ receptor agonist – migraine
• Propofol hemisuccinate (EP-102; EP-103) – GABA_A receptor positive allosteric modulator (propofol prodrug) – migraine
• Topiramate oral suspension – various actions – migraine

Not under development

Preregistration submission withdrawal

• Frovatriptan (Allegro; Auradol; EN-3266; Frova; Isimig; Migard; Pitunal; Rilamig; SB-209509; SB-209509AX; VML-251) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – menstrual migraine

Suspended

• Zolmitriptan transdermal (M-207; Qtrypta; triptan microneedle patch) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – cluster headache, migraine

No development reported

• AF-130 – purinergic P2X3 receptor antagonist – migraine
• B-244 (AOB-101; AOB-102; AOB-103; AOB-201; AOB-202; AOB-203; B244; nitrosomonas eutropha D23) – bacteria replacement – migraine
• Carabersat (SB-204269) – undefined mechanism of action (anticonvulsant) – migraine
• CLE-500 – undefined mechanism of action – cluster headache
• CT-044 analogues - CERSCI Therapeutics – reactive oxygen species (ROS) inhibitor – migraine
• Cyclobenzaprine extended release (Amrix; Bonelax; EUR-1002) – tricyclic antidepressant (non-selective monoamine reuptake inhibitor and receptor modulator and other actions) – migraine
• Donepezil (Allydone; Aricept; E-2020; E-2022; Eranz) – acetylcholinesterase inhibitor – migraine
• Donitriptan mesilate (F-12640) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Estetrol (E4; Donesta) – estrogen (estrogen receptor agonist) – migraine
• Filorexant (MK-6096) – orexin OX₁ and OX₂ receptor antagonist – migraine
• Flunarizine (XEN-007) – calcium channel blocker, non-selective monoamine receptor modulator, other actions – migraine
• Ibudilast (AV-411; Eyevinal; Ibinal; KC-404; Ketas; MN-166; Pinatos) – phosphodiesterase PDE4 inhibitor – headache
• IPX-232 – undefined mechanism of action – migraine
• Ketamine hydrochloride intranasal – ionotropic glutamate NMDA receptor antagonist and dissociative hallucinogen – cluster headache
• Ondansetron/rizatriptan oral transmucosal film (rizatriptan/ondansetron; MSRX-202) – combination of ondansetron (serotonin 5-HT₃ receptor antagonist and antiemetic) and rizatriptan (triptan)
• Oxytocin (TI-001; TI-114; TNX-1900; TNX-2900) – oxytocin receptor agonist – headache
• 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
• Psilocybin (low-dose psilocybin; BPL-PSILO) – non-selective serotonin receptor agonist and psychedelic hallucinogen – headache
• Psilocybin (MYCO-001; MYCO-003) – non-selective serotonin receptor agonist and psychedelic hallucinogen – headache
• Psilocybin (SYNP-101; synthetic psilocybin) – non-selective serotonin receptor agonist and psychedelic hallucinogen – cluster headache, migraine
• Relutrigine (PRAX-562) – sodium channel blocker – headache
• Research programme: calcitonin gene-related peptide receptor antagonists - Merck (CGRP receptor antagonists; Imidazoazepanes; MK-2918; MK-8825) – calcitonin gene-related peptide receptor (CGRPR) antagonists
• Research programme: GPCR modulators - Nxera Pharma – various actions
• Research programme: migraine and pain therapeutics - NeurAxon – various actions – migraine
• Research programme: pain and migraine therapy - OptiNose (OPT-1005) – undefined mechanism of action – migraine
• Rizatriptan intranasal – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Rizatriptan oral film – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Salubrin (PH80; PH-80; ORG-39479) – vomeropherine – migraine
• Sumatriptan (Imigran Nasal Spray; Imitrex Nasal Spray) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – menstrual migraine
• Sumatriptan transmucosal (Omexa) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Zucapsaicin (cis-capsaicin; Civamide; Civanex; Dolorac; Neuroderm; Zuacta) – transient receptor potential cation channel subfamily V member 1 (TRPV1) agonist – cluster headache, migraine

Discontinued

• Alniditan (R-91274) – serotonin 5-HT_1B and 5-HT_1D receptor agonist – migraine
• Avitriptan (BMS-180048) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• 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
• BI-44370 (BI44370) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine
• Botulinum toxin A topical (RT-001) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine
• Carisbamate (Comfyde; JNJ-10234094; RWJ-333369; YKP-509) – unknown mechanism of action – migraine [11]
• Dasolampanel (NGX-426) – ionotropic glutamate AMPA and kainate receptor antagonist – migraine
• Dextromethorphan/quinidine (DXM/Q; AVP-923; Neurodex; Nuedexta; Zenvia) – combination of dextromethorphan (various actions) and quinidine (various actions) – migraine
• Dihydroergocryptine (SRN-001) – non-selective monoamine receptor modulator and ergoline – migraine
• Donitriptan (F-11356) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Dotarizine (Dotaricin; FI-6026) – calcium channel blocker and serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2C receptor antagonist – migraine
• Dronabinol (Δ⁹-THC; Δ⁹-tetrahydrocannabinol; Deltanyne; Elevat; Marinol) – cannabinoid CB₁ and CB₂ receptor agonist – migraine
• Ergotamine inhalation (Tempo-ergotamine) – non-selective monoamine receptor modulator and ergoline – migraine
• Esprolol – beta blocker (β-adrenergic receptor antagonist) – migraine
• 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
• (S)-Ethylisothiouronium diethylphosphate (Difetur; MTR-104; MTR-105; MTR-106; MTR-107; MTR-108; Raviclust; Ravimig; Raviten) – nitric oxide synthase (NOS) inhibitor
• Fremanezumab (Ajovy; LBR-101; PF-04427429; PF-4427429; RN-307; TEV-48125) – monoclonal antibody against calcitonin gene-related peptide (CGRP) – cluster headache, headache
• Gabapentin (CI-945; Gabapen; GOE-3450; Neurontin) – gabapentinoid (α₂δ subunit-containing voltage-gated calcium channel ligand) – migraine
• Gabapentin enacarbil (1838262; ASP8825; GSK-1838262; Horizant; Regnite; Solzira; XP13512) – gabapentinoid (α₂δ subunit-containing voltage-gated calcium channel ligand) – migraine
• Ganaxolone (CCD-1042; Ztalmy) – GABA_A receptor positive allosteric modulator and neurosteroid – migraine
• HTL-0022562 (BHV-3100; HTL-22562) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine
• IS-159 – serotonin 5-HT_1D receptor agonist – migraine
• Lacosamide (ADD-234037; Erlosamide; Harkoseride; SPM-927; SPM-929; Vimpat; Vimpato) – various actions – migraine
• Lanepitant (LY-303870) – neurokinin NK₁ receptor antagonist – migraine
• Lidocaine transdermal patch (ADL-87223; LidoPAIN) – sodium channel blocker – headache
• Lornoxicam (Bosporon; Chlortenoxicam; HN-10000; RO-139297; Safem; TS-110; Xefo) – COX inhibitor/NSAID – migraine
• LY-2300559 – metabotropic glutamate receptor 2 (mGluR₂) positive allosteric modulator and cysteinyl leukotriene receptor 1 (CysLTR1) antagonist – migraine [12]
• LY-334370 – serotonin 5-HT_1F receptor agonist and triptan – migraine
• MEDI-0618 – monoclonal antibody against protease-activated receptor 2 (PAR2) – migraine
• Olcegepant (BIBN-4096; BIBN-4096BS) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine
• Oxytocin (TI-001; TI-114; TNX-1900; TNX-2900) – oxytocin receptor agonist – migraine
• Perampanel (E-2007; ER-155055-90; Fycompa) – AMPA receptor antagonist – migraine
• PF-5180999 (PF-05180999) – phosphodiesterase PDE2 inhibitor – migraine
• PNU-142633 (PNU-142633F) – serotonin 5-HT_1D receptor agonist – cluster headache, headache, migraine
• Prochlorperazine inhalation (AZ-001) – typical antipsychotic (non-selective monoamine receptor modulator) – migraine
• Propisergide (ergalgin) – serotonin receptor modulator and ergoline – migraine
• Propofol phosphate (Neuprox; propofol prodrug) – GABA_A receptor positive allosteric modulator (propofol prodrug) – migraine
• Research programme: migraine therapy - Orexo (OX-40; OX641) – undefined mechanism of action – migraine
• Selurampanel (BGG-492; BGG-492A) – ionotropic glutamate AMPA and kainate receptor antagonist – migraine
• Sergolexole (LY-281067) – serotonin 5-HT₂ receptor antagonist and ergoline – migraine
• Telcagepant (MK-0974) – calcitonin gene-related peptide receptor (CGRPR) antagonist – migraine
• Tezampanel (LY-293558; NGX-424; PRN-001-01) – ionotropic glutamate AMPA and kainate receptor antagonist – migraine
• Tizanidine (AN-021A; AN-021; DS-103282; Sirdalud; Ternelin; Zanaflex) – α₂-adrenergic receptor agonist – migraine
• Tonabersat (SB-220453; USL-260; Xiflam) – connexin 43 (GJA1) inhibitor – migraine
• Zolmitriptan inhalation (CVT-427) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Zonisamide (AD-810; CI-912; Excegran; Kinaplase; PD-110843; Tremode; Trerief; Zonegran) – calcium channel blocker, sodium channel blocker, and other actions – migraine

Clinically used drugs

Approved drugs

COX inhibitors/NSAIDs

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

Triptans (serotonin 5-HT_1B and 5-HT_1D receptor agonists)

• Almotriptan (Almogran; Axert; LAS-31416) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Eletriptan (Relert; Relpax; UK-116044) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine, menstrual migraine
• Frovatriptan (Allegro; Auradol; EN-3266; Frova; Isimig; Migard; Pitunal; Rilamig; SB-209509; SB-209509AX; VML-251) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Naratriptan (Amerge; GR-85548; GR-85548A; Naramig; SMP-948) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Rizatriptan (L-705126; Maxalt; MK-0462; MK-462) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Rizatriptan oral film (INT-0008; RHB-103; Rizafilm; VersaFilm; RizaPort) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Sumatriptan (Imigran Nasal Spray; Imitrex Nasal Spray) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine
• Zolmitriptan (311-C90; 311C; AscoTop; BW-311C90; Zomig; Zomigon) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – cluster headache, menstrual migraine, migraine
• Zolmitriptan oral dispersible film (zolmitriptan ODF; Zolmitriptan PharmaFilm; Zolmitriptan RapidFilm; Zolmitriptan Renantos Schmelzfilm) – serotonin 5-HT_1B and 5-HT_1D receptor agonist and triptan – migraine

Ergolines (non-selective monoamine receptor modulators)

• Dihydroergotamine (DHE; INP-104; POD-DHE; Trudhesa) – non-selective monoamine receptor modulator and ergoline – migraine
• Dihydroergotamine mesilate intranasal (Atzumi; STS-101; TO-2070) – non-selective monoamine receptor modulator and ergoline – migraine
• Dihydroergotamine mesylate intranasal (Migranal) – non-selective monoamine receptor modulator and ergoline – migraine

Calcitonin gene-related peptide (CGRP) inhibitors

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

Combination drugs

• Butalbital/acetaminophen (Butapap) – combination of butalbital (GABA_A receptor positive allosteric modulator and barbiturate) and acetaminophen (analgesic)
• Ergotamine/caffeine (Cafergot) – combination of ergotamine (non-selective monoamine receptor modulator and ergoline) and caffeine (adenosine receptor antagonist)
• Ergotamine/chlorcyclizine/caffeine (Anervan) – combination of ergotamine (non-selective monoamine receptor modulator and ergoline), chlorcyclizine (antihistamine and other actions), and caffeine (adenosine receptor antagonist)
• Meloxicam/rizatriptan (AXS-07; Symbravo) – combination of meloxicam (COX inhibitor/NSAID) and rizatriptan (triptan)
• Naproxen sodium/sumatriptan (MT-400; SumaRT/Nap; Suvexx; Trexima; Treximet) – combination of naproxen (COX inhibitor/NSAID) and sumatriptan (triptan) – migraine
• Paracetamol/codeine/buclizine (Migraleve Yellow) – combination of paracetamol (analgesic) and codeine (opioid)
• Paracetamol/codeine/buclizine (Migraleve Pink) – combination of paracetamol (analgesic), codeine (opioid), and buclizine (antihistamine and other actions)
• Paracetamol/dichloralphenazone/isometheptene (Amidrine) – combination of paracetamol (analgesic), dichloralphenazone (phenazone (COX inhibitor/NSAID) and chloral hydrate (GABA_A receptor positive allosteric modulator)), and isometheptene (adrenergic receptor agonist)
• Paracetamol/metoclopramide (Paramax) – combination of paracetamol (analgesic) and metoclopramide (various actions)
• Sumatriptan/naproxen (Treximet) – combination of sumatriptan (triptan) and naproxen (COX inhibitor/NSAID)

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-HT_1F receptor agonist – migraine
• Lomerizine (DE-090; KB-2796; Migsis) – non-selective monoamine receptor modulator, other actions – migraine
• Onabotulinum toxin A (BoNTA; Botox; GSK-1358820; OnabotA X; Vistabel; Vistabex) – acetylcholine release inhibitor and neuromuscular blocking agent – migraine
• Oxetorone (Nocertone, Oxedix) – non-selective monoamine receptor modulator – migraine
• Topiramate (Epitomax; KW-6485; MCN-4853; RWJ-17021; Topamax; Topimax; Topina) – various actions – migraine
• Topiramate oral (Eprontia; ET-101) – various actions – migraine
• Topiramate extended-release (SPN-538; TPM XR; Trokendi XR; Trokesa) – various actions – migraine
• Valproate semisodium (Depakote; Divalproex; Divalproex sodium; Epival; LA40220) – various actions – migraine

Off-label drugs

• α₂-Adrenergic receptor agonists (e.g., clonidine, tizanidine) ^{[15] [16] [17]}
• Acetaminophen (paracetamol) ^[18]
• Adenosine receptor antagonists (e.g., caffeine) ^{[19] [18]}
• Angiotensin-converting-enzyme inhibitors (ACE inhibitors) (e.g., lisinopril) ^[17]
• Angiotensin receptor antagonists (e.g., candesartan, telmisartan) ^[17]
• Antipsychotics and related (e.g., prochlorperazine, metoclopramide, haloperidol, promethazine, chlorpromazine) ^{[20] [21] [22] [23]}
• Anticonvulsants (e.g., valproic acid) ^[24]
• Barbiturates (e.g., butalbital, proxibarbital) ^{[25] [26]}
• Beta blockers (β-adrenergic receptor antagonists) (e.g., propranolol, metoprolol, nadolol, timolol, atenolol) ^{[27] [17]}
• Calcium channel blockers (e.g., verapamil, nimodipine, nifedipine, diltiazem) ^[17]
• Cannabinoids (cannabinoid receptor agonists) (e.g., cannabis, tetrahydrocannabinol (THC)) ^{[28] [29] [30]}
• Corticosteroids (e.g., dexamethasone, prednisone) ^{[31] [32]}
• Ergoline monoamine receptor modulators (e.g., ergotamine, methylergometrine, methysergide, dihydroergocryptine, bromocriptine, lisuride) ^{[33] [34] [35]}
• Estrogens (estrogen receptor agonists) (e.g., estradiol, ethinylestradiol) ^{[36] [37]}
• Gabapentinoids (α₂δ subunit-containing volate-gated calcium channel ligands) (e.g., gabapentin, pregabalin) ^{[38] [24]}
• Melatonin ^{[39] [40]}
• Nonsteroidal anti-inflammatory drugs (NSAIDs; COX inhibitors) (e.g., ibuprofen, aspirin, naproxen, diclofenac, ketorolac, ketoprofen) ^{[41] [18]}
• Opioids (μ-opioid receptor agonists) (e.g., morphine, codeine, oxycodone, hydrocodone) ^{[42] [43]}
• Progestogens (progesterone receptor agonists) (e.g., progesterone, medroxyprogesterone acetate) ^{[37] [13]}
• Propofol ^{[44] [45]}
• Serotonergic psychedelics (e.g., psilocybin, lysergic acid diethylamide (LSD), dimethyltryptamine (DMT)) ^{[46] [47] [48]}
• Serotonin receptor antagonists (e.g., methysergide, pizotifen, cyproheptadine) ^{[49] [50]}
• Sodium channel blockers (e.g., lidocaine) ^[51]
• Tetracyclic antidepressants (TeCAs) (e.g., mianserin, mirtazapine) ^{[50] [52]}
• Tricyclic antidepressants (TCAs) (e.g., amitriptyline, nortriptyline, imipramine) ^{[53] [54]}

See also

• List of investigational drugs
• Antimigraine drug
• Management of migraine

References

1. Devadoss, Thangaraj; Pingili, Ravindra Babu (2024). "Drugs Under Clinical Trials for the Treatment of Migraine". Management of Migraine Pain. Singapore: Springer Nature Singapore. p. 229–249. doi:10.1007/978-981-97-4529-6_12. ISBN   978-981--974528-9 . Retrieved 1 October 2025. The AGX-201 is chemically 2-(4-imidazolyl)ethylamine dihydrochloride, refer to Fig. 12.7 for the chemical structure. [...] AGX-201 is a dihydrochloride salt of histamine. [...]
2. Pellesi L, Do TP, Hougaard A (April 2024). "Pharmacological management of migraine: current strategies and future directions". Expert Opin Pharmacother. 25 (6): 673–683. doi:10.1080/14656566.2024.2349791. PMID   38720629. AGX-201 is a histamine receptor modulator that acts as an antagonist at H1 receptors and an agonist at H3 receptors. This dual mechanism of action offer a unique approach to mitigate migraine symptoms by reducing the release of proinflammatory neuropeptides from trigeminal nerve endings. Subcutaneous AGX-201 is currently tested in a phase II trial (NCT02021474) enrolling subjects with migraine requiring prophylactic treatment.
3. "A Phase 1 clinical trial of NYPRG-101 in healthy adult participants - AdisInsight". adisinsight.springer.com.
4. "Ceruvia Lifesciences Announces First Participant Dosed in BOL-148 Phase 1 Clinical Trial". BioSpace. 17 January 2023. Retrieved 29 October 2024.
5. Michael Haichin (2024). "Psychedelics Drug Development Tracker". Psychedelic Alpha. Retrieved 29 January 2025.
6. "BETR 001 - AdisInsight". adisinsight.springer.com.
7. "Delving into the Latest Updates on Bromolysergide with Synapse". synapse.patsnap.com.
8. Lewis V, Bonniwell EM, Lanham JK, Ghaffari A, Sheshbaradaran H, Cao AB, Calkins MM, Bautista-Carro MA, Arsenault E, Telfer A, Taghavi-Abkuh FF, Malcolm NJ, El Sayegh F, Abizaid A, Schmid Y, Morton K, Halberstadt AL, Aguilar-Valles A, McCorvy JD (March 2023). "A non-hallucinogenic LSD analog with therapeutic potential for mood disorders". Cell Rep. 42 (3) 112203. doi:10.1016/j.celrep.2023.112203. PMC   10112881 . PMID   36884348.
9. "Tactogen Inc – Pipeline". Tactogen Inc. 8 February 2021. Retrieved 29 January 2025.
10. WOpatent 2023183613A2, Matthew J. Baggott,"Indolizine compounds for the treatment of mental disorders or inflammation",published 2023 September 28, assigned to Tactogen 
11. Novak GP, Kelley M, Zannikos P, Klein B (January 2007). "Carisbamate (RWJ-333369)". Neurotherapeutics. 4 (1): 106–109. doi:10.1016/j.nurt.2006.11.016. PMC   7479705 . PMID   17199023.
12. Johnson, K. W.; Smith, A. C.; Davis, R. J.; Schkeryantz, J. M.; Johnson, M. P. (1 August 2013). "Preclinical Characterization of LY2300559, a Dual Acting mGlu2 Receptor Positive Allosteric Modulator (PAM) and Leukotriene CysLT1 Receptor Antagonist, for Potential Use as a Migraine Therapy". Cephalalgia. SAGE: 975. ISSN   0333-1024 . Retrieved 19 September 2025.
13. Lundberg PO (6 December 2012). "Endocrinology of Headache: A Review". In Pfaffenrath V, Lundberg PO, Sjaastad O (eds.). Updating in Headache. Springer Science & Business Media. pp. 229–. ISBN   978-3-642-88581-5.
14. Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 560–. ISBN   978-1-4757-2085-3.
15. Freitag FG (2003). "Preventative treatment for migraine and tension-type headaches: do drugs having effects on muscle spasm and tone have a role?". CNS Drugs. 17 (6): 373–381. doi:10.2165/00023210-200317060-00001. PMID   12696998.
16. Rau JC, Dodick DW (March 2019). "Other Preventive Anti-Migraine Treatments: ACE Inhibitors, ARBs, Calcium Channel Blockers, Serotonin Antagonists, and NMDA Receptor Antagonists". Curr Treat Options Neurol. 21 (4) 17. doi:10.1007/s11940-019-0559-0. PMID   30880363.
17. Carcel C, Haghdoost F, Shen J, Nanda P, Bai Y, Atkins E, Torii-Yoshimura T, Clough AJ, Davies L, Cordato D, Griffiths LR, Balicki G, Wang X, Vidyasagar K, Malavera A, Anderson CS, Zagami AS, Delcourt C, Rodgers A (June 2023). "The effect of blood pressure lowering medications on the prevention of episodic migraine: A systematic review and meta-analysis". Cephalalgia. 43 (6) 03331024231183166: 3331024231183166. doi:10.1177/03331024231183166. PMID   37350141.
18. Diener HC, Gaul C, Lehmacher W, Weiser T (January 2022). "Aspirin, paracetamol (acetaminophen) and caffeine for the treatment of acute migraine attacks: A systemic review and meta-analysis of randomized placebo-controlled trials". Eur J Neurol. 29 (1): 350–357. doi:10.1111/ene.15103. PMID   34519136.
19. Lipton RB, Diener HC, Robbins MS, Garas SY, Patel K (October 2017). "Caffeine in the management of patients with headache". J Headache Pain. 18 (1) 107. doi: 10.1186/s10194-017-0806-2 . PMC   5655397 . PMID   29067618.
20. Leong LB, Kelly AM (March 2011). "Are butyrophenones effective for the treatment of primary headache in the emergency department?". CJEM. 13 (2): 96–104. doi:10.2310/8000.2011.100301. PMID   21435315.
21. Orr SL, Aubé M, Becker WJ, Davenport WJ, Dilli E, Dodick D, Giammarco R, Gladstone J, Leroux E, Pim H, Dickinson G, Christie SN (March 2015). "Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings". Cephalalgia. 35 (3): 271–284. doi:10.1177/0333102414535997. PMID   24875925.
22. Weinman D, Nicastro O, Akala O, Friedman BW (February 2014). "Parenteral treatment of episodic tension-type headache: a systematic review". Headache. 54 (2): 260–268. doi:10.1111/head.12287. PMID   24433525.
23. Kelley NE, Tepper DE (February 2012). "Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others". Headache. 52 (2): 292–306. doi:10.1111/j.1526-4610.2011.02070.x. PMID   22309235.
24. Parikh SK, Silberstein SD (March 2019). "Current Status of Antiepileptic Drugs as Preventive Migraine Therapy". Curr Treat Options Neurol. 21 (4) 16. doi:10.1007/s11940-019-0558-1. PMID   30880369.
25. Silberstein SD, McCrory DC (2001). "Butalbital in the treatment of headache: history, pharmacology, and efficacy". Headache. 41 (10): 953–967. doi:10.1046/j.1526-4610.2001.01189.x. PMID   11903523.
26. Wenzel RG, Sarvis CA (August 2002). "Do butalbital-containing products have a role in the management of migraine?". Pharmacotherapy. 22 (8): 1029–1035. doi:10.1592/phco.22.12.1029.33595. PMID   12173787.
27. Fumagalli C, Maurizi N, Marchionni N, Fornasari D (January 2020). "β-blockers: Their new life from hypertension to cancer and migraine". Pharmacol Res. 151 104587. doi:10.1016/j.phrs.2019.104587. PMID   31809852.
28. Chandwani B, Bradley BA, Pace A, Buse DC, Singh R, Kuruvilla D (September 2023). "The Exploration of Cannabis and Cannabinoid Therapies for Migraine". Curr Pain Headache Rep. 27 (9): 339–350. doi:10.1007/s11916-023-01144-z. PMID   37515745.
29. Kuruvilla DE (June 2025). "Cannabinoids in headache: helpful or harmful?". Curr Opin Neurol. 38 (3): 277–280. doi:10.1097/WCO.0000000000001364. PMID   40152937.
30. Duarte RA, Dahmer S, Sanguinetti SY, Forde G, Duarte DP, Kobak LF (October 2021). "Medical Cannabis for Headache Pain: a Primer for Clinicians". Curr Pain Headache Rep. 25 (10) 64. doi:10.1007/s11916-021-00974-z. PMID   34628531.
31. Woldeamanuel YW, Rapoport AM, Cowan RP (December 2014). "What is the evidence for the use of corticosteroids in migraine?". Curr Pain Headache Rep. 18 (12) 464. doi:10.1007/s11916-014-0464-x. PMID   25373608.
32. Shapiro RE (April 2005). "Corticosteroid treatment in cluster headache: evidence, rationale, and practice". Curr Pain Headache Rep. 9 (2): 126–131. doi:10.1007/s11916-005-0050-3. PMID   15745623.
33. Dahlöf C, Maassen Van Den Brink A (April 2012). "Dihydroergotamine, ergotamine, methysergide and sumatriptan - basic science in relation to migraine treatment". Headache. 52 (4): 707–714. doi:10.1111/j.1526-4610.2012.02124.x. PMID   22444161.
34. Rapoport AM (April 2012). "What happens to the old headache medicines?". Headache. 52 (4): 701–706. doi:10.1111/j.1526-4610.2012.02123.x. PMID   22486742.
35. Akerman S, Goadsby PJ (November 2007). "Dopamine and migraine: biology and clinical implications". Cephalalgia. 27 (11): 1308–1314. doi:10.1111/j.1468-2982.2007.01478.x. PMID   17970991.
36. Reddy N, Desai MN, Schoenbrunner A, Schneeberger S, Janis JE (March 2021). "The complex relationship between estrogen and migraines: a scoping review". Syst Rev. 10 (1) 72. doi: 10.1186/s13643-021-01618-4 . PMC   7948327 . PMID   33691790.
37. Martin VT, Behbehani M (March 2006). "Ovarian hormones and migraine headache: understanding mechanisms and pathogenesis--part 2". Headache. 46 (3): 365–386. doi:10.1111/j.1526-4610.2006.00370.x. PMID   16618254.
38. Linde M, Mulleners WM, Chronicle EP, McCrory DC (June 2013). "Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults". Cochrane Database Syst Rev. 2013 (6) CD010609. doi:10.1002/14651858.CD010609. PMC   6599858 . PMID   23797675.
39. Gelfand AA, Goadsby PJ (September 2016). "The Role of Melatonin in the Treatment of Primary Headache Disorders". Headache. 56 (8): 1257–1266. doi:10.1111/head.12862. PMC   5012937 . PMID   27316772.
40. Long R, Zhu Y, Zhou S (January 2019). "Therapeutic role of melatonin in migraine prophylaxis: A systematic review". Medicine (Baltimore). 98 (3) e14099. doi:10.1097/MD.0000000000014099. PMC   6370052 . PMID   30653130.
41. Holland S, Silberstein SD, Freitag F, Dodick DW, Argoff C, Ashman E (April 2012). "Evidence-based guideline update: NSAIDs and other complementary treatments for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 78 (17): 1346–1353. doi:10.1212/WNL.0b013e3182535d0c. PMC   3335449 . PMID   22529203.
42. Levin M (January 2014). "Opioids in headache". Headache. 54 (1): 12–21. doi:10.1111/head.12266. PMID   24127913.
43. Stone MT, Weed V, Kulich RJ (September 2016). "Opioid Treatment of Migraine: Risk Factors and Behavioral Issues". Curr Pain Headache Rep. 20 (9) 51. doi:10.1007/s11916-016-0581-9. PMID   27474093.
44. Dhir A (September 2016). "Propofol in the treatment of refractory migraine headaches". Expert Rev Neurother. 16 (9): 1007–1011. doi:10.1080/14737175.2016.1216795. PMID   27454834.
45. Piatka C, Beckett RD (February 2020). "Propofol for Treatment of Acute Migraine in the Emergency Department: A Systematic Review". Acad Emerg Med. 27 (2): 148–160. doi:10.1111/acem.13870. PMID   31621134.
46. Henderson I, Elsaadany R, Chan G, Bajaj V, Duarte D, Goodman S, Grunstein M, Vadhan NP, Duarte RA (January 2025). "Exploring the Potential of Psychedelics in the Treatment of Headache Disorders: Clinical Considerations and Exploratory Insights". Curr Pain Headache Rep. 29 (1) 28. doi:10.1007/s11916-024-01321-8. PMID   39820774.
47. Im JJ, Sandoe CH (August 2025). "Psychedelics and Headache Disorders: an Update". Curr Neurol Neurosci Rep. 25 (1) 57. doi:10.1007/s11910-025-01446-2. PMID   40782223.
48. Govare A, Leroux E (May 2014). "Licit and illicit drug use in cluster headache". Curr Pain Headache Rep. 18 (5) 413. doi:10.1007/s11916-014-0413-8. PMID   24715619.
49. Segelcke D, Messlinger K (April 2017). "Putative role of 5-HT2B receptors in migraine pathophysiology". Cephalalgia. 37 (4): 365–371. doi:10.1177/0333102416646760. PMID   27127104.
50. Mylecharane EJ (1991). "5-HT2 receptor antagonists and migraine therapy". J Neurol. 238 Suppl 1: S45–52. doi:10.1007/BF01642906. PMID   2045831.
51. Berk T, Silberstein SD (May 2018). "The Use and Method of Action of Intravenous Lidocaine and Its Metabolite in Headache Disorders". Headache. 58 (5): 783–789. doi:10.1111/head.13298. PMID   29536530.
52. Bendtsen L, Jensen R (June 2006). "Tension-type headache: the most common, but also the most neglected, headache disorder". Curr Opin Neurol. 19 (3): 305–309. doi:10.1097/01.wco.0000227043.00824.a9. PMID   16702840.
53. Burch R (March 2019). "Antidepressants for Preventive Treatment of Migraine". Curr Treat Options Neurol. 21 (4) 18. doi:10.1007/s11940-019-0557-2. PMID   30895388.
54. Tomkins GE, Jackson JL, O'Malley PG, Balden E, Santoro JE (July 2001). "Treatment of chronic headache with antidepressants: a meta-analysis". Am J Med. 111 (1): 54–63. doi:10.1016/s0002-9343(01)00762-8. PMID   11448661.

External links

• AdisInsight - Springer