Aims We compared the vasoconstrictor effects of 5-HT with those of the selective 5-HT 1B/1D -receptor agonists sumatriptan and rizatriptan in human isolated cranial (middle meningeal) arteries. In addition selective 5-HT 1B -or 5-HT 1D -receptor antibodies were used in combination with semiquantitative immunohistochemical techniques to compare the levels of expression of these receptors in human middle meningeal and coronary arteries. Methods Middle meningeal and coronary arteries were obtained (with consent) from either neurosurgical patients or donor hearts, respectively. Segments of middle meningeal artery were mounted in organ baths for isometric recording and cumulative concentration-effect curves to 5-HT, rizatriptan and sumatriptan were obtained. Frozen fresh sections of middle meningeal and coronary arteries were subjected to standard immunohistochemical techniques using specific 5-HT 1B -or 5-HT 1D -receptor primary antibodies and a radiolabelled secondary antibody. Data were subjected to analysis of variance (anova) and nonlinear regression analysis.Results 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC 50 values=32, 90 and 71 nm, respectively). A significantly higher level of 5-HT 1B -receptor immunoreactivity was detected in middle meningeal artery compared with coronary artery (anova, F=7.95, DF= 1,4, P<0.05). Conclusions Rizatriptan and sumatriptan act selectively to cause vasoconstriction in human isolated middle meningeal artery and are 10-fold more potent than in human coronary artery. The higher level of expression of 5-HT 1B -receptors in middle meningeal compared with coronary artery provides a pharmacological basis for the craniovascular selectively of both rizatriptan and sumatriptan.Keywords: 5-HT 1B/1D -receptor agonists, human arteries, vasoconstriction importance since this may lead to coronary adverse events Introduction [12, 13]. It has been reported that 5-HT 1B -receptors mediate vasoconstriction in cranial/cerebral arteries and also in It is generally accepted that migraine headache is accompanied by excessive vasodilation of extracerebral, coronary arteries [4][5][6]. However, sumatriptan acts selectively in cranial arteries compared with coronary arteries since the intracranial blood vessels and that the therapeutic action of 5-HT 1B/1D -receptor agonists such as sumatriptan can result, incidence of cardiac adverse-events related to sumatriptan administration in migraineurs is rare. at least in part, from cranial vasoconstriction [1-3] via activation of vascular 5-HT 1B -receptors [4][5][6][7]. (Note in this Previously we have reported two independent coronary artery studies (using different experimental protocols) where report we follow the recently adopted nomenclature of 5-HT 1B -and 5-HT 1D -receptors, however, these subtypes the maximum contraction evoked by the selective 5-HT 1B/1D -receptor agonist rizatriptan was found to be signifiare also known in the literature as 5-HT 1Db and 5-HT 1Da receptors, respectivel...