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Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy
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Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy
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Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy
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Journal Article
Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery – potential antimigraine efficacy
2019
Overview
BackgroundRacemic 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.MethodsHuman 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.ResultsThe 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.ConclusionThe 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.
Publisher
Springer Nature B.V
