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

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


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.

Original languageEnglish
Article number47
JournalThe Journal of Headache and Pain Online
Issue number1
Pages (from-to)47
Publication statusPublished - 2019
Externally publishedYes


  • Adult
  • Animals
  • Calcitonin Gene-Related Peptide/pharmacology
  • Coronary Vessels/drug effects
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Meningeal Arteries/drug effects
  • Methylamines/chemistry
  • Middle Aged
  • Migraine Disorders/drug therapy
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Saphenous Vein/drug effects
  • Stereoisomerism
  • Vasoconstrictor Agents/chemistry
  • Vasodilation/drug effects
  • Vasodilator Agents/chemistry
  • Organ baths
  • Vasodilation
  • Migraine
  • Isometheptene
  • CGRP
  • Isolated vessels


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