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 language | English |
|---|---|
| Pages (from-to) | 3649-3665 |
| Number of pages | 17 |
| Journal | Current Medicinal Chemistry |
| Volume | 24 |
| Issue number | 33 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
Fingerprint
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 journal › Review article
}
TY - JOUR
T1 - Migraine, Neurogenic Inflammation, Drug Development - Pharmacochemical Aspects
AU - Lukacs, Melinda
AU - Tajti, J.
AU - Fülöp, F.
AU - Toldi, J.
AU - Edvinsson, Lars
AU - Vécsei, L.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
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.
KW - calcitonin-gene related peptide
KW - kynurenic acid
KW - migraine
KW - Neurogenic inflammation
KW - pituitary adenylate cyclase activating polypeptide
KW - trigeminovascular system
UR - http://www.scopus.com/inward/record.url?scp=85039861559&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039861559&partnerID=8YFLogxK
U2 - 10.2174/0929867324666170712163437
DO - 10.2174/0929867324666170712163437
M3 - Review article
C2 - 28707585
AN - SCOPUS:85039861559
VL - 24
SP - 3649
EP - 3665
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 33
ER -