Headache induced by serotonergic agonists--a key to the interpretation of migraine pathogenesis?

Cephalalgia. 1997 Feb;17(1):3-14. doi: 10.1046/j.1468-2982.1997.1701003.x.


Serotonergic agonists such as m-chlorophenylpiperazine (m-CPP) and fenfluramine may induce migraine attacks. This has led to opposing theories concerning the role of 5-hydroxytryptamine (5HT) in triggering migraine attacks; is there hyperfunction or hypofunction of the central serotonergic system. Our review of the literature strongly suggests that m-CPP and fenfluramine provoke migraine attacks by stimulating, directly or indirectly, the 5HT2C/5HT2B receptors, although there is no total agreement with this interpretation. Central 5HT hypersensitivity in migraine patients, probably due to 5HT neuronal depletion, is proposed on the basis of review of electrophysiological tests and neuroendocrine challenge paradigms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Fenfluramine / adverse effects*
  • Fenfluramine / pharmacology
  • Headache / chemically induced*
  • Headache / drug therapy
  • Headache / etiology
  • Humans
  • Hypersensitivity
  • Piperazines / adverse effects*
  • Piperazines / pharmacology
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology
  • Serotonin Antagonists / pharmacology
  • Serotonin Antagonists / therapeutic use
  • Serotonin Receptor Agonists / adverse effects*
  • Serotonin Receptor Agonists / pharmacology


  • Piperazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Fenfluramine
  • 1-(3-chlorophenyl)piperazine