Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Melinda Lukacs, J. Tajti, F. Fülöp, J. Toldi, Lars Edvinsson, L. Vécsei

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase-activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in the modulation of inflammatory mechanisms.

OBJECTIVE: To review the literature focusing on novel therapeutic targets in migraine, related to neurogenic inflammation.

METHOD: A systematic literature search in the database of PUBMED was conducted regarding therapeutic strategies in migraine, focusing on substances and cytokines released during neurogenic inflammation, published until January 2017.

RESULTS: Ongoing phase III clinical studies with monoclonal antibodies against CGRP and CGRP receptors offer promising novel aspects for migraine treatment. Preclinical and clinical studies targeting SP and nitric oxide synthase (NOS) were all terminated with no significant results compared to placebo. New promising therapeutic goal could be PACAP and its receptor (PAC1), and kynurenic acid (KYNA) analogues.

CONCLUSION: Current migraine treatment offers pain relief only for a small proportion of migraine patients and might not be adequate for patients with cardiovascular comorbidity due to side effects. Better understanding of migraine pathophysiology might, therefore, lead to novel therapeutic lines both in migraine attack treatment and prophylaxis.

Original languageEnglish
Pages (from-to)3649-3665
Number of pages17
JournalCurrent Medicinal Chemistry
Volume24
Issue number33
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Neurogenic Inflammation
Calcitonin Gene-Related Peptide
Substance P
Migraine Disorders
Pituitary Adenylate Cyclase-Activating Polypeptide Receptors
Calcitonin Gene-Related Peptide Receptors
Kynurenic Acid
Pituitary Adenylate Cyclase-Activating Polypeptide
Vasoactive Intestinal Peptide
Neuropeptides
Nitric Oxide Synthase
Pharmaceutical Preparations
Neurons
Neurotransmitter Agents
Glutamic Acid
Nitric Oxide
Chemical activation
Monoclonal Antibodies
Modulation
Cytokines

Keywords

  • calcitonin-gene related peptide
  • kynurenic acid
  • migraine
  • Neurogenic inflammation
  • pituitary adenylate cyclase activating polypeptide
  • trigeminovascular system

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects. / Lukacs, Melinda; Tajti, J.; Fülöp, F.; Toldi, J.; Edvinsson, Lars; Vécsei, L.

In: Current Medicinal Chemistry, Vol. 24, No. 33, 01.01.2017, p. 3649-3665.

Research output: Contribution to journalReview article

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AB - BACKGROUND: Migraine is a primary headache disorder. Despite numerous studies conducted with the aim to understand the pathophysiology of migraine, several aspects are still unclear. The trigeminovascular system plays a key role. Neurogenic inflammation is presumed to be an important factor in migraine pathophysiology, mediated by the activation of primary neurons, leading to the release of various pro-inflammatory neuropeptides and neurotransmitters such as Calcitonin Gene-Related Peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Nitric oxide (NO), Pituitary adenylate cyclase-activating polypeptide (PACAP) and Glutamate (Glu) also play an important role in the modulation of inflammatory mechanisms.OBJECTIVE: To review the literature focusing on novel therapeutic targets in migraine, related to neurogenic inflammation.METHOD: A systematic literature search in the database of PUBMED was conducted regarding therapeutic strategies in migraine, focusing on substances and cytokines released during neurogenic inflammation, published until January 2017.RESULTS: Ongoing phase III clinical studies with monoclonal antibodies against CGRP and CGRP receptors offer promising novel aspects for migraine treatment. Preclinical and clinical studies targeting SP and nitric oxide synthase (NOS) were all terminated with no significant results compared to placebo. New promising therapeutic goal could be PACAP and its receptor (PAC1), and kynurenic acid (KYNA) analogues.CONCLUSION: Current migraine treatment offers pain relief only for a small proportion of migraine patients and might not be adequate for patients with cardiovascular comorbidity due to side effects. Better understanding of migraine pathophysiology might, therefore, lead to novel therapeutic lines both in migraine attack treatment and prophylaxis.

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