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S.J. Peroutka, MD, PhD, Spectra Biomedical Inc, Menlo Park, Calif, advocates using dopamine antagonists with serotonin agonists in treating migraine. Optimal management probably depends on correcting inflammation, increasing dopamine, and decreasing 5-HT levels. Aspirin and other nonsteroidal antiinflammatory agents (NSAIDs) help in acute migraine attacks. Sumatriptan (SUMA), a specific 5-HT type 1 agonist, gave clinicians another drug to provide symptomatic relief. Peroutka reviewed the roles of dopamine and 5-HT in acute migraine. A modulated balance of these neurotransmitters may lead to improved control.

Serotonin (5-HT) and migraine As migraine symptoms worsen, 5-HT levels decrease. Intracranial blood vessels dilate resulting in a decrease in blood flow. Left alone, symptoms improve and the attack stops by return of generated 5-HT. Stimulation of 5-HT type 1 receptors by medications hastens recovery. 5-HT agonists seem ineffective during migraine aura and fail to correct brainstem pathology as seen in positron emission tomography (PET) scans. Headache recurrence may be as high as 50 percent using 5-HT agonists alone.
Dopamine and migraine Peroutka asks whether it is the increase in dopamine that triggers and maintains a migraine attack. This chemical participates in controlling cerebral blood flow, nausea, emesis, and gastric motility--all malfunctioning during a migraine attack.

Bromocriptine, a dopamine agonist, produces a predictable dose-related series of clinical signs. Yawning is the first to appear. Increasing the dose induces mood changes, nausea, gastrokinetic changes, hypotension, vomiting, and lastly dyskinesia. Migraineurs yawned four times more often per hour and showed a higher incidence of headache than controls after 0.25 mg sublingual apomorphine, another dopamine agonist (Headache 1994;34:536-538).

Gastric dilatation occurs during a migraine attack. The presence of dopamine receptors in the stomach helps explain the accompanying decrease in gastric tone, peristalsis, emptying, and disrupted gastroduodenal coordination. Dopamine antagonists reverse these effects.

Using dopamine antagonists in migraine In 1977, Hughes reported that 10 mg metoclopramide, a dopamine antagonist, relieved the nausea and headache in 3 of 4 patients having an acute attack (Med J Aust 1977; 2:580).

Open-label emergency room data suggest that injections of dopamine antagonists relieve acute migraine attacks. A review on 534 patients, 6 to 213 patients per report, gave an average efficacy rate of 83 percent, including migraine headache. Peroutka listed the following dopamine antagonists with corresponding levels of efficacy: haloperidol, 100%; chlorpromazine, 93%; droperidol, 91%; methotrimeprazine, 82%; procloperazine, 86%; flunarzine, 76%; and metoclopramide, 60%.

Rationale for using dopamine antagonists Peroutka gives 5 reasons for such treatment of acute migraine:

  • reduction of nausea and vomiting

  • restoration of gastric motility

  • increased absorption of concurrent medications

  • cost-effectiveness

  • correction of the metabolic abnormality of a migraine attack

Conclusions Modulating brain dopamine and 5-HT in migraineurs mirrors the approach used in treating hypertension with blood pressure and cholesterol lowering agents. In migraine, there is a need, according to Peroutka, to increase 5-HT or stimulate 5-HT type 1 receptors and to block or lower dopamine.
For professional correspondence, please contact Dr. Peroutka at: Fax (415) 617-9008.

Eugene A. Conrad

Presented at Thirty-ninth Annual Scientific Meeting, American Association for the Study of Headache (AASH), June 19-22, 1997
Copyright © 1997 Conrad Group, Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / September 1997

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