44 research outputs found
Lasmiditan inhibits calcitonin gene-related peptide release in the rodent trigeminovascular system
Migraine headache pathophysiology involves trigeminovascular system activation, calcitonin gene-related peptide (CGRP) release, and
dysfunctional nociceptive transmission. Triptans are 5-HT1B/1D/(1F) receptor agonists that prejunctionally inhibit trigeminal CGRP release,
but their vasoconstrictor properties limit their use in migraine patients with cardiovascular disease. By contrast, lasmiditan is a novel
antimigraine and selective 5-HT1F receptor agonist devoid of vasoconstrictor properties. On this basis, this study has investigated the
modulation of trigeminal CGRP release by lasmiditan. For this purpose, we have comparatively analysed the inhibition of several
components of the trigeminovascular system induced by lasmiditan and sumatriptan through: ex vivo KCl-induced CGRP release from
isolated dura mater, trigeminal ganglion, and trigeminal nucleus caudalis of mice; and in vivo dural vasodilation in the rat closed-cranial
window model induced by endogenous (electrical stimulation and capsaicin) and exogenous CGRP. The ex vivo release of CGRP was
similarly inhibited by sumatriptan and lasmiditan in all trigeminovascular system components. In vivo, intravenous (i.v.) lasmiditan or higher
doses of sumatriptan significantly attenuated the vasodilatory responses to endogenous CGRP release, but not exogenous CGRP
effects. These data suggest that lasmiditan prejunctionally inhibits CGRP release in peripheral and central trigeminal nerve terminals.
Because lasmiditan is a lipophilic drug that crosses the blood–brain barrier, additional central sites of action remain to be determined
Effects of two isometheptene enantiomers in isolated human blood vessels and rat middle meningeal artery - potential antimigraine efficacy
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
Bile acid effects are mediated by ATP release and purinergic signalling in exocrine pancreatic cells
Additional file 1: Figure S1. of Dural administration of inflammatory soup or Complete Freund’s Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion
Representative Western blot. The figure shows a representativce Western blot for the data that are presented in Fig. 6. (TIFF 2843 kb