New targets in the acute treatment of headache

The aim of this article is to review recently identified targets for the acute treatment of primary headache disorders.

Calcitonin gene-related peptide (CGRP) receptor blockade has been shown to be an effective acute anti-migraine strategy and is a non-vasoconstrictor in terms of the mechanism of action. It is likely that direct blockade of CGRP release by inhibition of trigeminal nerves would be similarly effective in both migraine and cluster headache. Options for acute treatment based on preclinical work and initial clinical studies include: serotonin 5HT1F and 5HT1D receptor agonists, glutamate excitatory amino acid receptor antagonists, nitric oxide synthase inhibitors and adenosine A1 receptor agonists. Proof of principle studies with octreotide, a somatostatin receptor agonist, demonstrated it to be better than placebo in the acute treatment of cluster headache but not in the acute management of migraine.

The prospect of a non-vasoconstrictor acute migraine therapy offers a real opportunity to patients, and perhaps more importantly, provides a therapeutic rationale to plant migraine and cluster headache firmly in the brain as neurological problems.