Naratriptan has a selective inhibitory effect on trigeminovascular neurones at central 5-HT1A and 5-HT(1B/1D) receptors in the cat: implications for migraine therapy.
The triptans are agonists at serotonin (5-HT)1B/1D receptors; however, they are also active at 5-HT1A and 5-HT1F receptors. We conducted this series of experiments to further elucidate the site of action of naratriptan using a well-established animal model of trigeminovascular stimulation. Following electrical stimulation of the superior sagittal sinus of the cat, single cell responses (n=83) were recorded in the trigeminal nucleus caudalis. Most cells (91%) also responded to electrical and mechanical stimulation of cutaneous or mucosal facial receptive fields. The microiontophoretic application of naratriptan resulted in a significant suppression of the response to sagittal sinus stimulation (response suppressed by 47 +/- 4%, P<0.001). The effect of naratriptan was significantly attenuated by application of either the 5-HT(1B/1D) receptor antagonist GR-127935 (P<0.001) or the 5-HT1A antagonist WAY-100635 (P<0.05). The response of single cells to receptive field stimulation was also suppressed by microiontophoretic application of naratriptan, but by only 20 +/- 3%. Intravenous administration of naratriptan resulted in a similar selective suppression of sagittal sinus vs. receptive field responses in trigeminal neurones. These results indicate that naratriptan has a central effect in the trigeminovascular system, selectively inhibiting afferent activity in craniovascular neurones, via both 5-HT(1B/1D) and 5-HT1A receptors.
Boers
P M
PM
Faculty of Medicine, The University of New South Wales and Institute of Neurological Sciences, The Prince Henry and Prince of Wales Hospitals, Sydney, Australia. BoersP@sesahs.nsw.gov.au
Donaldson
C
C
Zagami
A S
AS
Lambert
G A
GA
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology*; D008839:Microelectrodes; D008881:Migraine Disorders / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010812:Physical Stimulation; D010880:Piperidines / Q000494:pharmacology*; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D014275:Trigeminal Caudal Nucleus / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D014363:Tryptamines
D007211:Indoles; D010880:Piperidines; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C106783:naratriptan