Investigation of the Effects of Naratriptan,Rizatriptan,and Sumatriptan on Jugular Venous Oxygen Saturation in Anesthetized Pigs:Implications for Their Mechanism of Acute Antimigraine Action

摘要

The effects of naratriptan,rizatriptan,and sumatriptan on arteriovenous oxygen saturation difference and carotid hemodynamics were compared in the anesthetized pig.Oxygen and carbon dioxide partial pressures in systemic arterial and jugular venous blood as well as hemoglobin oxygen saturation were determined by conventional blood gas analysis.Vehicle (n=19) or naratriptan,rizatriptan,or sumatriptan (0.63,2.5,10,40,160,630,and 2,500 mug/kg i.v.;n=7/group) were infused cumulatively.In naratriptan-rizatriptan-,and sumatriptan-treated animals,jugular venous oxygen saturationdecreased dose dependently (geometric mean ED_(50) values of 3.1,17,9,and 16.0 mug/kg,respectively) concomitantly with increases in crotid vascula resistance.Rizatriptan significantly and dose dependently,from 160 mug/kg,increased PvCO_2 (P<0.05 versus vehicle).Nratriptan and sumatriptan also tended to increase PvCO_2 albeit nonstatistically significantly.All three triptans consistently evoked quantitatively similar carotid vasoconstriction,whereas decreases in jugular venous oxygen saturation (VOS) and increases in PvCO_2 had different magnitudes and occurred only in around one-half of the animals studied.maximal variations of PvCO_2 were found to correlated highly with those in PvO_2 (P=0.002),but maximal variations in carotid resistance failed to correlate with those in PvCO_2 (P=0.76) or PvO_2 (P=0.28).The results demonstrate that the triptans investigated robustly produced carotid vasoconstriction,but elicited less consistent decreases in VOS and increases in jugular PvCO_2,possibly suggestive of distinct mechanisms.Collectively,the data suggest that triptan-induced increases in arteriovenous oxygen saturation difference and carbon dioxide partial pressure in venous blood draining the head are class effects.