The 5-hydroxytryptamine1B/1D/1F receptor agonists eletriptan and naratriptan inhibit trigeminovascular input to the nucleus tractus solitarius in the cat.
Migraine pain arises in the trigeminovascular system and is often associated with nausea and sometimes with vomiting. In this study, an in vivo cat model of trigeminovascular stimulation was used to determine first whether there is a functional connection between the trigeminovascular system and the nucleus tractus solitarius (NTS), which is involved in regulating vomiting, and second whether anti-migraine drugs have any effect on such a connection. Chloralose-anaesthetised cats (n=16) were prepared for single neuron recording. The superior sagittal sinus (SSS) was isolated and stimulated electrically. The brainstem near the obex was exposed and a metal microelectrode equipped with six glass barrels for microiontophoresis was placed in the NTS. Recordings were made from 44 NTS neurons which responded to SSS stimulation with A-delta latencies. Iontophoretic ejection (50 nA) of eletriptan or naratriptan suppressed the response in 75% (15/20) and 78% (11/14) of cells and caused an average suppression of cell firing of 42+/-5% (n=20) and 54+/-8% (n=14), respectively. This suppression could be antagonized by the concurrent ejection (20-50 nA) of the 5-HT(1B/1D) receptor antagonist GR127935. We conclude that activation of the trigeminovascular system excites cells in the NTS that can be inhibited by eletriptan and naratriptan through activation of 5-HT(1B/1D) receptors. It is possible that in patients having a migraine attack trigeminovascular activation triggers nausea and vomiting, and that the alleviation of these symptoms by anti-migraine compounds may be via an action at 5-HT(1B/1D) receptors in the NTS.
Hoskin
Karen Lisa
KL
Institute of Neurological Sciences, Prince of Wales Hospital, University of New South Wales, G39 Clinical Sciences Bldg. High St. Randwick NSW, Sydney 2031, Australia.
Lambert
Geoffrey Andrew
GA
Donaldson
Cathy
C
Zagami
Alessandro Stefano
AS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002415:Cats; D004347:Drug Interactions; D004558:Electric Stimulation; D007211:Indoles / Q000494:pharmacology*; D020714:Maximum Tolerated Dose; D009433:Neural Inhibition / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology; D014278:Trigeminal Nuclei / Q000187:drug effects* / Q000502:physiology; D014363:Tryptamines; D000096642:Receptor, Serotonin, 5-HT1F
D007211:Indoles; D010069:Oxadiazoles; D010879:Piperazines; D010880:Piperidines; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D058825:Serotonin 5-HT1 Receptor Agonists; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D000096642:Receptor, Serotonin, 5-HT1F; C115647:eletriptan; C090701:GR 127935; C106783:naratriptan