Table 2:

Drugs used to treat or prevent migraine with putative sites of action

	Year of introduction for clinical use	Acute or preventive drug	Forms of administration	Type of drug	Mechanism of action	Possible sites of action
Ergotamines*	1926	Acute	Intravenous; nasal spray; oral	5-HT1B,1D,1F receptor agonist	Inhibits peptide release	Prejunctional receptors
Triptans	1991	Acute	Nasal spray; oral; sublingual; subcutaneous	5-HT1B,1D/1F receptor agonist	Disrupt communication between peripheral and central trigeminovascular neurons	Prejunctional receptors; presynaptic inhibition at the dorsal horn
OnabotulinumtoxinA	2010	Preventive	Intramuscular; subcutaneous	Cleaves intracellular SNARE proteins	Cleaves SNAP25 and prevents adhesion of synaptic vesicles to the cell surface membrane, resulting in inhibition of neuropeptides or neurotransmitter release, and insertion of new receptors	Unmyelinated C-class trigeminovascular meningeal nociceptors; unmyelinated C-class cervicovascular extracranial nociceptors
Monoclonal antibodies†	2018	Preventive	Subcutaneous; intravenous	CGRP-receptor antagonist	Neutralises circulating neuropeptides (or peptide receptor blockade)	Trigeminal ganglion; meningeal nociceptors
Ditans‡	Not yet introduced	Acute	Oral	5-HT1F receptor agonist	Inhibits peptide release	Central sites and peripheral prejunctional receptors
Gepants§	Not yet introduced	Acute and preventive	Oral	CGRP-receptor antagonist	Peptide receptor blockade	Trigeminal ganglion; meningeal nociceptors; spinal trigeminal nucleus

5-HT=hydroxytryptamine (serotonin). SNARE=soluble NSF attachment protein receptor. CGRP=calcitonin gene-related peptide. PACAP=pituitary adenylate cyclase-activating peptide.

^*Ergotamines are non-selective for 5-HT and are active at adrenergic and other receptor sites.

^†Anti-PACAP38 monoclonal antibodies are in pre-clinical development and will be administered subcutaneously. Anti-PAC₁ receptor antibodies are awaiting public results from phase II trials.

^‡The first ditan (lasmiditan) is expected to be approved by the US Food and Drugs Administration in 2019.

^§The first gepants (rimegepant and ubrogepant) are expected to be approved by the US Food and Drugs Administration in 2019 or 2020.