Indomethacin increases the effect of isosorbide dinitrate on cerebral hemodynamic in migraine patients: pathogenetic and therapeutic implications

Cephalalgia. 1998 Nov;18(9):622-30. doi: 10.1046/j.1468-2982.1998.1809622.x.


Intracerebral vascular reactivity induced by the nitric oxide (NO) donor isosorbide dinitrate (IDN, 5 mg sublingually) is more major and longer-lasting in migraine patients who develop delayed headache in response to the drug. The headache is purportedly due to neuronally-mediated vascular mechanisms. Indomethacin inhibits prostaglandin synthesis, which is involved in NO generation. Indomethacin also decreases cerebral blood flow by constricting precapillary resistance vessels. In the present study, the hemodynamic effects of indomethacin were evaluated in migraine patients and healthy controls by means of transcranial Doppler monitoring. Indomethacin caused a significant decrease in mean flow velocity in the middle cerebral artery. This was an additional effect to the mean velocity decrease induced by IDN. The interactions between the two drugs suggest that their effects on cerebral hemodynamics (and pain) may be of relevance both in understanding the role of NO in migraine pathogenesis and in evaluating symptomatic treatments for migraine attacks.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Cerebrovascular Circulation / drug effects*
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Indomethacin / pharmacology*
  • Indomethacin / therapeutic use
  • Isosorbide Dinitrate / pharmacology*
  • Male
  • Middle Aged
  • Migraine Disorders / chemically induced*
  • Migraine Disorders / drug therapy*
  • Migraine Disorders / physiopathology
  • Nitric Oxide / physiology
  • Prostaglandin Antagonists / pharmacology*
  • Prostaglandin Antagonists / therapeutic use
  • Prostaglandins / physiology
  • Ultrasonography, Doppler, Transcranial
  • Vasodilator Agents / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Prostaglandin Antagonists
  • Prostaglandins
  • Vasodilator Agents
  • Nitric Oxide
  • Isosorbide Dinitrate
  • Indomethacin