Drugs targeting nitric oxide synthase for migraine treatment

Piero Barbanti, Gabriella Egeo, Cinzia Aurilia, Luisa Fofi, David Della Morte

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Introduction: Ample evidence that nitric oxide (NO) is a causative molecule in migraine has encouraged research to develop drugs that target the NO-cGMP cascade for migraine treatment. NO synthase (NOS) inhibition is an innovative therapeutic principle.Areas covered: This paper reviews the rationale underlying NOS inhibition in migraine treatment. It also provides a review on the efficacy and safety data for NOS inhibitors (nonselective NOS inhibitor L-N G-methyl-arginine hydrochloride [L-NMMA], selective inducible NOS [iNOS] inhibitors GW273629 and GW274150, combined neuronal NOS [nNOS] inhibitor and 5-HT1B/1D receptor agonist NXN-188) in acute or preventive migraine treatment.Expert opinion: The data highlighted herein, from four placebo-controlled trials and 1 open-labeled clinical trial using 4 different NOS inhibitors on a total of 705 patients, provide convincing efficacy data only for the nonselective NOS inhibitor L-NMMA. Unfortunately, this NOS inhibitor raises cardiovascular safety concerns and has an unfavorable pharmacokinetic profile. As experimental studies predicted, iNOS inhibitors are ineffective in migraine. Still, upcoming selective nNOS inhibitors are a hope for migraine treatment, with the nNOS isoform being most clearly involved in trigeminovascular transmission and central sensitization. Future studies should help to clarify whether NOS inhibition is equally fruitful in acute and preventive treatment. It should also clarify if nNOS inhibition holds promise as a therapeutic tool for the treatment of chronic migraine and other forms of headache.

Original languageEnglish
Pages (from-to)1141-1148
Number of pages8
JournalExpert Opinion on Investigational Drugs
Volume23
Issue number8
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Drug Delivery Systems
Migraine Disorders
Nitric Oxide Synthase
omega-N-Methylarginine
Therapeutics
Nitric Oxide
Receptor, Serotonin, 5-HT1B
Central Nervous System Sensitization
Safety
Expert Testimony
Headache
Arginine
Protein Isoforms
Pharmacokinetics
Placebos
Clinical Trials
Research
Pharmaceutical Preparations

Keywords

  • Headache
  • Migraine
  • Nitric oxide
  • Nitric oxide synthases inhibitors
  • Treatment

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Drugs targeting nitric oxide synthase for migraine treatment. / Barbanti, Piero; Egeo, Gabriella; Aurilia, Cinzia; Fofi, Luisa; Della Morte, David.

In: Expert Opinion on Investigational Drugs, Vol. 23, No. 8, 01.01.2014, p. 1141-1148.

Research output: Contribution to journalArticle

Barbanti, Piero ; Egeo, Gabriella ; Aurilia, Cinzia ; Fofi, Luisa ; Della Morte, David. / Drugs targeting nitric oxide synthase for migraine treatment. In: Expert Opinion on Investigational Drugs. 2014 ; Vol. 23, No. 8. pp. 1141-1148.
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