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Naratriptan has a selective inhibitory effect on trigeminovascular neurones at central 5-HT1A and 5-HT1B/1D receptors in the cat: implications for migraine therapy

Authors

  • Pm Boers,

    1. Faculty of Medicine, The University of New South Wales and Institute of Neurological Sciences, The Prince Henry and Prince of Wales Hospitals, Sydney, Australia
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  • C Donaldson,

    1. Faculty of Medicine, The University of New South Wales and Institute of Neurological Sciences, The Prince Henry and Prince of Wales Hospitals, Sydney, Australia
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  • As Zagami,

    1. Faculty of Medicine, The University of New South Wales and Institute of Neurological Sciences, The Prince Henry and Prince of Wales Hospitals, Sydney, Australia
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  • Ga Lambert

    1. Faculty of Medicine, The University of New South Wales and Institute of Neurological Sciences, The Prince Henry and Prince of Wales Hospitals, Sydney, Australia
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Dr Peter Boers, Department of Neurology, St. George Hospital, Belgrave Street, Kogarah, NSW 2217, Australia. Tel. +61 2 9350 2491, fax +61 2 9350 2211, e-mail BoersP@sesahs.nsw.gov.au

Abstract

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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-HT1B/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-HT1B/1D and 5-HT1A receptors.

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