Comparative effects of frovatriptan and sumatriptan on coronary and internal carotid vascular haemodynamics in conscious dogs

1 The effects of frovatriptan and sumatriptan on internal carotid and coronary vascular haemodynamics were investigated and compared in conscious dogs. 2 Frovatriptan and sumatriptan (0.1-100 mug kg(-1)) induced a transient increase in external coronary artery diameter (eCOD) of up to 2.9+/-1.2 and 1.8+/-0.6%, respectively (both P<0.05). This was followed by a prolonged and dose-dependent decrease in eCOD of up to -5.2+/-1.2 and -5.3+/-0.9% (both P<0.05), with ED50 values of 86+/-21 and 489+/-113 mu mol kg(-1), respectively. In contrast, only a decrease in the external diameter of the internal carotid artery was observed (-6.0+/-0.6 and -6.2+/-1.4%, both P<0.05, and ED50 values of 86+/-41 and 493+/-162 mol kg(-1) respectively). Frovatriptan was thus 5.7 fold more potent than sumatriptan at the level of both large coronary and internal carotid arteries. 3 After endothelium removal by balloon angioplasty in coronary arteries, the initial dilatation induced by the triptans was abolished and delayed constriction enhanced. 4 The selective antagonist for the 5-HT1B receptors SB224289 dose-dependently blocked the effects of sumatriptan on large coronary and internal carotid arteries whereas the selective antagonist for the 5-HT1D receptors BRL15572 did not affect any of these effects. 5 In conclusion, frovatriptan and sumatriptan initially dilate and subsequently constrict large coronary arteries in the conscious dog, whereas they directly constrict the internal carotid artery. The vascular endothelium modulates the effects of these triptans on large coronary arteries. Finally, 5-HT1B but not 5-HT1D receptors are primarily involved in canine coronary and internal carotid vasomotor responses to sumatriptan.