The 5-HT 1D/1B agonists, Triptans, are used for a Migraine headache. A migraine is characterized by nausea, vomiting and visual scotomas or even hemianopsia and speech abnormalities.

Migraine involves the trigeminal nerve distribution to instracranial, and possibly extracranial, arteries. These nerve release peptide neurotansmitters, especially calcitonin gene-related peptide, CGRP, an extremely powerful vasodilator. Substance P and neurokinin A may also be involved.

The triptans, ergot alkaloids and antidepressants may activate 5-HT 1D/B receptors on presynaptic trigeminal nerve endings to inhibit the release of vasodilating peptides and antiseizure agents may suppress excessive firing of these nerve endings. The vasoconstrictor actions of direct 5—HT agonists, the triptans and ergot, may prevent vasodilation and stretching of the pain endings. It is possible that both mechanisms contribute in the case of some drugs.

Sumatriptan and its congeners are currently first in line therapy for acute severe migraine attacks in most patients. They activate these receptors on the presynaptic trigeminal nerve ends to inhibit the release of the vasodilating peptides.

Anti-inflammatory analgesics such as aspirin and ibuprofen are often used to control the pain of migraine and not resolving the migraine itself.