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- Title
Possible antimigraine mechanisms of action of the 5HT<sub>1F</sub> receptor agonist LY334370.
- Authors
Shepheard, S; Edvinsson, L; Cumberbatch, M; Williamson, D; Mason, G; Webb, J; Boyce, S; Hill, R; Hargreaves, R
- Abstract
This study investigated whether the selective 5HT1F receptor agonist LY334370 has other possible antimigraine mechanisms in addition to the proposed inhibition of dural plasma extravasation. LY334370 (up to 10-5 M) had no vasoconstrictor effects on human cerebral arteries in vitro. It had no effect (up to 10 mg kg-1 iv) on neurogenic vasodilation of dural blood vessels produced by electrical stimulation of the dura mater in anesthetized rats. Nor had it any effect (at 3 mg kg-1 , iv) on the hvperalgesia produced by injection of carrageenan into the paw of conscious rats or on nociceptive reflex responses in the spinalized,decerebrate rabbit (up to 3 mg kg-1 , iv), indicating that it has no general analgesic properties. However, it significantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in anesthetised rats at 3 mg kg-1 , iv. These results provide evidence to suggest that LY334370 has a central mechanism of action in blocking the transmission of nociceptive impulses within the trigeminal nucleus caudalis and that this may represent a mechanism through which it has its antimigraine effect.
- Publication
Cephalalgia, 1999, Vol 19, Issue 10, p851
- ISSN
0333-1024
- Publication type
Academic Journal
- DOI
10.1046/j.1468-2982.1999.1910851.x