Ergotamines and Beta-blockers: Theory of Vasodilation

For a long time, people thought that problems with the blood vessels in the brain caused migraine. The theory was that blood vessels in the brain stretched and widened, causing pain. A drug that could constrict (narrow) the blood vessels might help. This has been called the “vascular theory of migraine.”

Migraine's connection to blood vessels

In 1938, a doctor named Harold Wolff did an experiment to test this theory. He compared headache intensity with throbbing in the arteries. He treated patients in his study with ergotamine. Ergotamine constricts the blood vessels. He showed that as the throbbing went down, so did the headache pain.1

Today, we believe there is more to the story than overexcited blood vessels. But for years, migraine was treated using drugs that affected blood flow in the brain.

Ergotamine: Acute treatment (1930s to 1990s)

Ergotamine was a relatively new drug when Dr. Wolff started his experiments. It had been studied in France in 1928 and then was brought to the United States.2 Doctors were studying it as a treatment for all kinds of conditions.

Trials at the time were small and not very rigorous. One doctor studied 45 patients with migraine, another studied nine. One large study included 109 migraineurs.2 None of them had a placebo group for comparison. Ergotamine seemed to help most of the patients most of the time. It became a standard acute (or abortive) treatment for migraine.2Ergotamine is still used today in some circumstances. It is less popular now that triptans are available.

DHE (dihydroergotamine)

DHE (dihydroergotamine) is related to ergotamine. It was introduced in 1943 and has also been used to treat migraine since then.2

Unfortunately, ergotamine and DHE have unpleasant side effects. Nausea and vomiting are common.3 Some people experience leg weakness, muscle pain, numbness, and tingling in the fingers and toes.3 It can cause uterine contractions and affects the blood vessels of the heart. Ergotamine can cause medication overuse headache. There was a clear need for effective acute treatment with fewer side effects.

Beta-blockers: Preventive treatment (1960s onward)

In the 1960s, doctors started using beta-blockers for the preventive treatment of chronic migraine.4 Beta-blockers are heart drugs, but doctors noticed they were also useful for preventing migraines. They believed that the beta-blockers worked because of their effect on blood flow in the brain.4 It still is not entirely clear why these medications help to prevent migraine.

Beta-blockers are still used in some patients today. The three beta-blockers with the most evidence for preventing migraine are:5

  • Metoprolol (Lopressor®, Toprol® XL)
  • Propranolol (Inderal® LA, Inderal® XL, InnoPran® XL)
  • Timolol

Read more on the history of migraine treatments in this article.

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Written by Editorial Team | Reviewed March 2022

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