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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects

Author(s): Melinda Lukacs, Janos Tajti, Ferenc Fulop, Jozsef Toldi, Lars Edvinsson and Laszlo Vecsei*

Volume 24, Issue 33, 2017

Page: [3649 - 3665] Pages: 17

DOI: 10.2174/0929867324666170712163437

Price: $65

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.

Keywords: Neurogenic inflammation, trigeminovascular system, calcitonin-gene related peptide, pituitary adenylate cyclase activating polypeptide, kynurenic acid, migraine.

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