Evidence for serotonin (5-HT)1B, 5-HT1D and 5-HT1F receptor inhibitory effects on trigeminal neurons with craniovascular input.
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 alpha-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 micros 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.
Goadsby
P J
PJ
Headache Group, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk
Classey
J D
JD
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D004558:Electric Stimulation / Q000379:methods; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D044346:Receptor, Serotonin, 5-HT1D / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D012886:Skull / Q000098:blood supply / Q000187:drug effects; D014276:Trigeminal Nerve / Q000187:drug effects / Q000502:physiology*; D000096642:Receptor, Serotonin, 5-HT1F
D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000096642:Receptor, Serotonin, 5-HT1F