Targeted Nitric Oxide Synthase Inhibitors for Migraine

Amynah A. Pradhan, Zachariah Bertels, Simon Akerman

Research output: Contribution to journalReview articlepeer-review

85 Scopus citations


Nitric oxide (NO) is a small gaseous signaling molecule that has important biological effects. It has been heavily implicated in migraine; and the NO donor, nitroglycerin, has been used extensively as a human migraine trigger. Correspondingly, a number of components of the NO signaling cascade have been shown to be upregulated in migraine patients. NO is endogenously produced in the body by NO synthase (NOS), of which there are three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Based on the accumulating evidence that endogenous NO regulation is altered in migraine pathogenesis, global and isoform-selective inhibitors of NOS have been targeted for migraine drug development. This review highlights the evidence for the role of NO in migraine and focuses on the use of NOS inhibitors for the treatment of this disorder. In addition, we discuss other molecules within the NO signaling pathway that may be promising therapeutic targets for migraine.

Original languageEnglish
Pages (from-to)391-401
Number of pages11
Issue number2
StatePublished - Apr 1 2018


  • Guanylyl cyclase
  • Headache
  • Migraine
  • Nitric oxide synthase
  • Pain


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