The Journal of Headache and Pain
Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy
The Journal of Headache and PainOfficial Journal of the "European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"201920:47
© The Author(s). 2019
- Received: 9 March 2019
- Accepted: 22 April 2019
- Published: 3 May 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.
Keywords
- CGRP
- Isolated vessels
- Isometheptene
- Migraine
- Organ baths
- Vasodilation
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