Possible antimigraine mechanisms of action of the 5HT(1F) receptor agonistLY334370

This study investigated whether the selective 5HT(1F) receptor agonist LY33 4370 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 eff ect (up to 10 mg kg(-1), iv) on neurogenic vasodilation of dural blood vess els produced by electrical stimulation of the dura mater in anesthetized ra ts. Nor had it any effect (at 3 mg kg(-1), iv) on the hyperalgesia produced by injection of carrageenan into the paw of conscious rats or on nocicepti ve reflex responses in the spinalized, decerebrate rabbit (up to 3 mg kg-l, iv), indicating that it has no general analgesic properties. However, it s ignificantly inhibited activation of second-order neurons in the trigeminal nucleus caudalis produced by electrical stimulation of the dura mater in a nesthetised rats at 3 mg kg(-1), iv. These results provide evidence to sugg est that LY334370 has a central mechanism of action in blocking the transmi ssion of nociceptive impulses within the trigeminal nucleus caudalis and th at this may represent a mechanism through which it has its antimigraine eff ect.