Joint 1994 Wolff Award Presentation. Peripheral and central trigeminovascular activation in cat is blocked by the serotonin (5HT)-1D receptor agonist 311C90.
Migraine headache involves the activation of trigeminal afferents that are predominantly found in the first or ophthalmic division of the nerve. The headache is often pounding and the connections of the trigeminal nerve, the trigeminovascular system, have therefore been implicated in the pathophysiology of migraine and studied extensively. Considerable attention has been given to the peripheral ramifications of the system as a possible locus of action for anti-migraine drugs while little attention has been focused upon possible central sites of action. It has been shown that certain peptides can act as markers for the trigeminal system, in particular calcitonin gene-related peptide (CGRP), and that CGRP is elevated in migraine. We have employed an animal model for activation of the trigeminovascular system to evaluate a new antimigraine compound, 311C90, that may have central and as well as peripheral trigeminal actions. Cats were anesthetized by halothane induction and alpha-chloralose maintenance (60 mg/kg, intraperitoneal), intubated, paralyzed and ventilated. Biparietal craniotomies were carried out to measure cerebral blood flow using laser Doppler flowmetry (CBFLDF). The external jugular vein was cannulated and blood drawn, centrifuged and frozen until processing. Stimulation of the trigeminal ganglion resulted in a mean maximum increase in CBFLDF of 39 +/- 5% at 20/s. The 5HT1 agonist 311C90 was administered intravenously in two doses (30 and 100 micrograms/kg) to cover the range of doses likely to be effective clinically. At each dose the CBFLDF effect of trigeminal ganglion stimulation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)
Goadsby
P J
PJ
Department of Neurology, Prince Henry Hospital, Sydney, NSW, Australia.
Edvinsson
L
L
D000818:Animals; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000097:blood; D010080:Oxazoles / Q000494:pharmacology*; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012668:Trigeminal Ganglion / Q000187:drug effects* / Q000502:physiology; D014363:Tryptamines
D009479:Neuropeptides; D010080:Oxazoles; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan