1 The observation that 5-hydroxytryptamine (5-HT) is e ective in treating acute attacks of migraine when administered intravenously resulted in a research e ort that led to the discovery of the 5-HT 1B/1D receptor agonist sumatriptan. 2 Clinical experience has shown sumatriptan to be an e ective treatment with some limitations, such as relatively poor bioavailability, which naratriptan was developed to address. Increasing bioavailability has been achieved with greater lipophilicity and thus the potential for greater activity in the central nervous system. 3 In this study the increased access to central sites has been exploited in an attempt to characterize the pharmacology of those central receptors with the newer tools available. Trigeminovascular activation was examined in the model of superior sagittal sinus stimulation. 4 Cats were anaesthetized with a-chloralose (60 mg kg 71 , intraperitoneal), paralyzed (gallamine 6 mg kg 71 , intravenously) and ventilated. The superior sagittal sinus was accessed and isolated for electrical stimulation (250 ms pulses, 0.3 Hz, 100 V) by a mid-line circular craniotomy. The region of the dorsal surface of C 2 spinal cord was exposed by a laminectomy and an electrode placed for recording evoked activity from sinus stimulation. 5 Stimulation of the superior sagittal sinus resulted in activation of cells in the dorsal horn of C 2 . Cells ®red with a probability of 0.69+0.1 at a latency of 9.2+0.2 ms. Intravenous (i.v.) administration of naratriptan at clinically relevant doses (30 and 100 mg kg 71 ), inhibited neuronal activity in trigeminal neurones of the C 2 dorsal horn, reducing probability of ®ring without a ecting latency. 6 The e ect of naratriptan could be reversed by administration of the selective 5-HT 1B/1D receptor antagonist GR127935 (100 mg kg 71 , i.v.). 7 These data establish that naratriptan acts on central trigeminal neurones since sagittal sinus stimulation activates axons within the tentorial nerve and there are no inhibitory e ects mediated within the trigeminal ganglion. Furthermore, given that this inhibition could be reversed by the relatively selective 5-HT 1B/1D receptor antagonist GR127935, it is highly likely that the anti-migraine e ects of drugs of this class with central nervous system access are mediated, at least in part, by 5-HT 1B/1D receptors within the trigeminal nucleus.