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


RESULTS
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.


CONCLUSIONS
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.
Goadsby
Peter J
PJ
Headache Group, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK.
D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006261:Headache / Q000145:classification / Q000188:drug therapy* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000502:physiology; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology; D017481:Receptors, Somatostatin / Q000819:agonists / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D014276:Trigeminal Nerve / Q000187:drug effects
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D043682:Receptor, Adenosine A1; D018015:Receptors, Calcitonin Gene-Related Peptide; D011985:Receptors, Serotonin; D017481:Receptors, Somatostatin; D017366:Serotonin Receptor Agonists; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide