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Open Access 01-12-2019 | Migraine | Research article

Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy

Authors: Alejandro Labastida-Ramírez, Eloísa Rubio-Beltrán, Kristian A. Haanes, René de Vries, Ruben Dammers, A. J. J. C. Bogers, Antoon van den Bogaerdt, Bruce L. Daugherty, Alexander H. J. Danser, Carlos M. Villalón, Antoinette MaassenVanDenBrink

Published in: The Journal of Headache and Pain | Issue 1/2019

Abstract

Background

Racemic isometheptene [(RS)-isometheptene] is an antimigraine drug that due to its cardiovascular side-effects was separated into its enantiomers, (R)- and (S)-isometheptene. This study set out to characterize the contribution of each enantiomer to its vasoactive profile. Moreover, rat neurogenic dural vasodilatation was used to explore their antimigraine mechanism of action.

Methods

Human blood vessel segments (middle meningeal artery, proximal and distal coronary arteries, and saphenous vein) were mounted in organ baths and concentration response curves to isometheptene were constructed. Calcitonin gene-related peptide (CGRP)-induced neurogenic dural vasodilation was elicited in the presence of the enantiomers using a rat closed cranial window model.

Results

The isometheptene enantiomers did not induce any significant contraction in human blood vessels, except in the middle meningeal artery, when they were administered at the highest concentration (100 μM). Interestingly in rats, (S)-isometheptene induced more pronounced vasopressor responses than (R)-isometheptene. However, none of these compounds affected the CGRP-induced vasodilator responses.

Conclusion

The isometheptene enantiomers displayed a relatively safe peripheral vascular profile, as they failed to constrict the human coronary artery. These compounds do not appear to modulate neurogenic dural CGRP release, therefore, their antimigraine site of action remains to be determined.

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Title: Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy
Authors: Alejandro Labastida-Ramírez
Eloísa Rubio-Beltrán
Kristian A. Haanes
René de Vries
Ruben Dammers
A. J. J. C. Bogers
Antoon van den Bogaerdt
Bruce L. Daugherty
Alexander H. J. Danser
Carlos M. Villalón
Antoinette MaassenVanDenBrink
Publication date: 01-12-2019
Publisher: Springer Milan
Keywords: Migraine
Capsaicin
Sumatriptan
Published in: The Journal of Headache and Pain / Issue 1/2019
Print ISSN: 1129-2369
Electronic ISSN: 1129-2377
DOI: https://doi.org/10.1186/s10194-019-1003-2

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Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy

Abstract

Background

Methods

Results

Conclusion

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Abstract

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