Mechanism/indication / Treatment / Current stage
Calcitonin gene-related peptide (CGRP) mechanism antagonist
CGRP receptor antagonist (gepant) / Olcegepant1
Telcagepant, acute2
Telcagepant, preventative3
Rimagepant4
BI44370TA5
MK-32076
MK-1602 (NCT01613248) / Phase II
Phase II
Phase II*
Phase II
Phase II
Phase II*
Phase II
CGRP antibody
CGRP receptor antibody / ALD-4037
LY-29517428
LDR-101/TEV-481259,10
AMG-33411 / Phase III
Phase III
Phase III
Phase III
Serotonin-related
5-HT1F receptor agonist (ditan) / Lasmiditan12 / Phase III
Nitric oxide synthase (NOS) inhibition
PanNOS
Inducible NOS
Neuronal NOS plus triptan / 546C8813
GW274150 acute14
GW274150 preventive15
NXN-18816,17 / Phase II
Phase II (F)
Phase II (F)
Phase II (F)
Glutamatergic targets
NMDA receptor migraine with prolonged aura
Prevention of aura, not headache
AMPA/kainate
iGluR5 (kainate) receptor
mGluR5 (glurants)
AMPA receptor antagonist / Ketamine18
Tonabersat19,20
Tezampanel/LY29355821
LY46619522
ADX1005923
BGG49224 / Phase II
Phase II
Phase II
Phase II
Phase II
Phase II (F)
Neuroinflammatory targets
TRPV1
Substance P/neurokinin-1
Neurogenic plasma protein extravasation (PPE) / SB-70549825
Dapitant26
Lanepitant27
GR20517128
L-758,29829
Lanepitant,30prevention
CP-122,28831
4991W9332 / Phase II (F)
Phase II (F)
Phase II (F)
Phase II (F)
Phase II (F)
Phase II (F)
Phase II (F)
Phase II (F)
Phase II (F)
Other targets
Orexin 1 and 2 receptors (rexants)
Angiotensin receptor / Filorexant33
Candesartan33,35
Telmisartan36 / Phase II (F)
Off-license
(F)
Emerging targets
Acid-sensing ion channel (ASICs)
Pituitary adenylate cyclase activating peptide (PACAP)
Neuronal NOS
Phosphodiesterase inhibition / Amiloride37
PACAP receptor antagonists38–40
Neuronal NOS inhibition41
Ibudilast42
Neuromodulation strategies
Transcranial magnetic stimulation (TMS)
Occipital nerve stimulation (ONS)
Transcutaneous vagal nerve stimulation
Supraorbital nerve stimulation
Sphenopalatine ganglion stimulation / Single pulse TMS43,44
Chronic migraine45–47
Gammacore device48,49
Cefaly50
ATI device (NCT01540799) / Marketed
Phase II (F)
Phase II (F)
Marketed
Phase II
(F): Study failed; * Liver toxicity led to termination of development
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