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 coron ary vascular haemodynamics were investigated and compared in conscious dogs . 2 Frovatriptan and sumatriptan (0.1-100 mug kg(-1)) induced a transient inc rease 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), respective ly. In contrast, only a decrease in the external diameter of the internal c arotid artery was observed (-6.0+/-0.6 and -6.2+/-1.4%, both P<0.05, and ED 50 values of 86+/-41 and 493+/-162 <mu>mol kg(-1) respectively). Frovatript an was thus 5.7 fold more potent than sumatriptan at the level of both larg e coronary and internal carotid arteries. 3 After endothelium removal by balloon angioplasty in coronary arteries, th e initial dilatation induced by the triptans was abolished and delayed cons triction enhanced. 4 The selective antagonist for the 5-HT1B receptors SB224289 dose-dependent ly blocked the effects of sumatriptan on large coronary and internal caroti d arteries whereas the selective antagonist for the 5-HT1D receptors BRL155 72 did not affect any of these effects. 5 In conclusion, frovatriptan and sumatriptan initially dilate and subseque ntly constrict large coronary arteries in the conscious dog, whereas they d irectly constrict the internal carotid artery. The vascular endothelium mod ulates the effects of these triptans on large coronary arteries. Finally, 5 -HT1B but not 5-HT1D receptors are primarily involved in canine coronary an d internal carotid vasomotor responses to sumatriptan.