Evidence for serotonin (5-HT) 1B, 5-HT 1D and 5-HT 1F receptor inhibitory effects on trigeminal neurons with craniovascular input

Abstract

Development of serotonin (5HT 1B/1D) agonists for the acute attack of migraine resulted in considerable interest in their action. The superior sagittal sinus (SSS) was isolated in α-chloralose (60 mg/kg, i.p. and 20 mg/kg i.v.i. supplementary 2 hourly) anaesthetised cats. The SSS was stimulated electrically (100 V, 250 μs duration, 0.3 Hz) and neurons of the trigeminocervical complex monitored using electrophysiological methods. To test 5-HT 1B receptor-mediated activity common carotid blood flow (CCF) was monitored with a transonic flow probe placed around the vessel. Naratriptan (5-HT 1B/1D/1F receptor agonist) and alniditan (5-HT 1B/1D receptor agonist) produced reductions in carotid blood flow of 38±5% and 42±6%, respectively. These effects were attenuated by the 5-HT 1B receptor antagonist SB224289 ( P<0.05). LY344864 (5-HT 1F receptor agonist) had no effect on CCF. Naratriptan inhibited SSS-evoked activity (61±7%), an effect partially inhibited by the 5-HT 1B receptor antagonist SB224289 (30±5%), or by the 5-HT 1D receptor antagonist BRL-15572 (37±6%). There remained an inhibitory effect of naratriptan after both 5-HT 1B and 5-HT 1D receptor blockade (22±5%). Alniditan inhibited SSS-evoked trigeminal activity (53±6%), an effect abolished after 5-HT 1B and 5-HT 1D receptor blockade. LY344864 (5-HT 1F receptor agonist) inhibited SSS-evoked trigeminal activity (28±5%), an effect unaltered by either SB224289 or BRL-15572. It can be concluded that there are inhibitory 5-HT 1B, 5-HT 1D and 5-HT 1F receptors in the trigeminocervical complex of the cat. 5-HT 1B receptor-mediated inhibition is the most potent of the three in terms of inhibition of trigeminovascular nociceptive traffic.