Donitriptan, but not sumatriptan, inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors.
OBJECTIVE
It has been suggested that during a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), resulting in cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the effects of the agonists sumatriptan (5-HT(1B/1D) water-soluble), donitriptan (5-HT(1B/1D) lipid-soluble), PNU-142633 (5-HT(1D) water-soluble) and PNU-109291 (5-HT(1D) lipid-soluble) on vasodilator responses to capsaicin, alpha-CGRP and acetylcholine in dog external carotid artery.


METHODS
59 vagosympathectomized dogs were anaesthetized with sodium pentobarbitone. Blood pressure and heart rate were recorded with a pressure transducer, connected to a cannula inserted into a femoral artery. A precalibrated flow probe was placed around the common carotid artery, with ligation of the internal carotid and occipital branches, and connected to an ultrasonic flowmeter. The thyroid artery was cannulated for infusion of agonists.


RESULTS
Intracarotid infusions of capsaicin, alpha-CGRP and acetylcholine dose-dependently increased blood flow through the carotid artery. These responses remained unaffected after intravenous (i.v.) infusions of sumatriptan, PNU-142633, PNU-109291 or physiological saline; in contrast, donitriptan significantly attenuated the vasodilator responses to capsaicin, but not those to alpha-CGRP or acetylcholine. Only sumatriptan and donitriptan dose-dependently decreased the carotid blood flow. Interestingly, i.v. administration of the antagonist, SB224289 (5-HT(1B)), but not of BRL15572 (5-HT(1D)), abolished the inhibition by donitriptan.


CONCLUSIONS
Our results suggest that the inhibition produced by donitriptan of capsaicin-induced external carotid vasodilatation is mainly mediated by 5-HT(1B), rather than 5-HT(1D), receptors, probably by a central mechanism.
Muñoz-Islas
E
E
Departamento de Farmacobiología, Cinvestav-Coapa, Czda. de los Tenorios 235, Col. Granjas-Coapa, México D.F., México.
Gupta
S
S
Jiménez-Mena
L R
LR
Lozano-Cuenca
J
J
Sánchez-López
A
A
Centurión
D
D
Mehrotra
S
S
MaassenVanDenBrink
A
A
Villalón
C M
CM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002342:Carotid Artery, External / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D009570:Nitriles / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects*; D044346:Receptor, Serotonin, 5-HT1D / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D018170:Sumatriptan / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D001578:Benzopyrans; D002839:Chromans; D009570:Nitriles; C112854:PNU 109291; D010879:Piperazines; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D017366:Serotonin Receptor Agonists; D014363:Tryptamines; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; C120143:donitriptan; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D002211:Capsaicin; C401885:PNU 142633F