Pathology of a migraine:

There are two types of migraines.

1. The classic migraine, characterized by:

• Vomiting
• Nausea
• Speech abnormalities
• Visual scotomas
• Hemianopsia

2. The common migraine, characterized by:

• Throbbing pain on one side of the head
• The pain is moderate to severe and worsens with normal physical activity
• Nausea
• Vomiting
• You may feel worse in the presence of light and sound
• The migraine lasts 4-72 hours if not treated

A migraine is a clear biological disorder of the CNS. The nerve distribution to intracranial and extracranial arteries are involved in a migraine. These nerves are responsible for pain transmission  signals. Calcitonin gene-related peptide (CGRP), stimulates the release of of peptide neurotransmitters and is a strong vasodilator.

Treatment of a migraine:

5-HT 1D/1B agonists

• Triptans: Sumatriptan (acute attacks), Almotriptan, Rizatriptan, Zolmitriptan (effect is shorter than with a headache, and there are different dossiges). Triptans are the first line drug therapy for acute severe migraines. Triptans should not be used in patients with coronary artery disease because they have the ability to cause coronary vasospasms. These drugs are selective agonists for 5-HT, 1D and 5-HT, 1B receptors. On the presynaptic trigeminal nerve ends they activate these receptors to inhibit the release of the vasodilating peptides.
• Ergot alkaloids: Ergotamine and Ergonovine are good examples. These drugs block alpha agonist vasoconstriction and cause a marked smooth muscle contraction. The ergot derivates have mixed partial agonist effects at 5-HT2 receptors and at alpha adrenoceptors.. The effects mentioned above helps to reduce the vasodilation which causes the migraine.
• Beta-blockers: Propranolol. Not for acute attacks, but only for prophylaxis.
• Anti-inflammatory analgesics: Aspirin and Ibuprofen. These drugs only control the pain of the migraine and don’t resolve the migraine.
• Anti-seizure agents: Supresses the excessive firing of the nerve endings
• Anti-depressants: Same working mechanism as ergot alkaloids. Amitriptyline is a good example.
• Anti-convulsanis: Flunarizine, for a severely acute attack.
• Lasmiditan: Highly selective 5-HT 1F receptor agonist which is effective in treating migraines. This agent is much more cardiovascular safe than the triptans. This drug reduces the trigeminal nerve stimulation-induced plasma and plasma protein extravasation in dura vessels. This drug is used in acute migraines.
• Calcium (CA2t) channel blockers: Flunarizine. For prophylaxis only.