Differential medication overuse risk of novel anti-migraine therapeutics.
Animals
Calcitonin Gene-Related Peptide Receptor Antagonists
/ pharmacology
Carbazoles
/ pharmacology
Fluorobenzenes
/ pharmacology
Headache Disorders, Secondary
/ drug therapy
Male
Mice
Mice, Inbred C57BL
Migraine Disorders
/ drug therapy
Pain Measurement
/ drug effects
Piperazines
/ pharmacology
Quinazolines
/ pharmacology
Receptors, Calcitonin Gene-Related Peptide
/ metabolism
Receptors, Serotonin
/ metabolism
Risk Factors
Receptor, Serotonin, 5-HT1F
headache: drug treatment
headache: experimental models
migraine
secondary headache
trigeminal ganglion
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
20
12
2019
revised:
07
04
2020
accepted:
03
05
2020
pubmed:
19
8
2020
medline:
17
2
2021
entrez:
19
8
2020
Statut:
ppublish
Résumé
Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it is critical to determine the risk profile of novel therapies prior to their widespread use. The current study explores the potential medication overuse risk of two novel therapeutic drug classes, namely the ditans: 5-HT1F receptor agonists, and the gepants: calcitonin gene-related peptide receptor antagonists, in a preclinical model of medication overuse. Persistent exposure of mice to the 5-HT1F agonist LY344864, but not olcegepant produced a significant reduction in hind paw and orofacial mechanical withdrawal thresholds as a surrogate readout of allodynia. In agreement, only LY344864 induced neuroplastic changes in trigeminal sensory afferents, increasing calcitonin gene-related peptide expression and basal trigeminal nociception. Our data highlight a differential medication overuse headache risk profile for the ditan and gepant classes of drugs that has important implications for their clinical use and patient education to help reduce the burden of medication overuse headache.
Identifiants
pubmed: 32810212
pii: 5894039
doi: 10.1093/brain/awaa211
pmc: PMC7523700
doi:
Substances chimiques
Calcitonin Gene-Related Peptide Receptor Antagonists
0
Carbazoles
0
Fluorobenzenes
0
LY 344864
0
Piperazines
0
Quinazolines
0
Receptors, Calcitonin Gene-Related Peptide
0
Receptors, Serotonin
0
olcegepant
WOA5J8TX6M
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2681-2688Subventions
Organisme : Wellcome Trust
ID : 104033
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P006264/1
Pays : United Kingdom
Organisme : NIDA NIH HHS
ID : R01 DA040688
Pays : United States
Informations de copyright
© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.
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