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.
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 microg/kg i.v.; n = 7/group) were infused cumulatively. In naratriptan-, rizatriptan-, and sumatriptan-treated animals, jugular venous oxygen saturation decreased dose dependently (geometric mean ED50 values of 3.1, 17.9, and 16.0 microg/kg, respectively) concomitantly with increases in carotid vascular resistance. Rizatriptan significantly and dose dependently, from 160 microg/kg, increased PvCO2 (P < 0.05 versus vehicle). Naratriptan and sumatriptan also tended to increase PvCO2 albeit nonstatistically significantly. All three triptans consistently evoked quantitatively similar carotid vasoconstriction, whereas decreases in jugular venous oxygen saturation (VOS) and increases in PvCO2 had different magnitudes and occurred only in around one-half of the animals studied. Maximal variations in PvCO2 were found to correlate highly with those in PvO2 (P = 0.002), but maximal variations in carotid resistance failed to correlate with those in PvCO2 (P = 0.76) or PvO2 (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 PvCO2, 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.
Létienne
Robert
R
Centre de Recherche Pierre Fabre, Castres, France.
Verscheure
Yvan
Y
John
Gareth W
GW
D000758:Anesthesia; D000818:Animals; D001784:Blood Gas Analysis; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007601:Jugular Veins / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy; D010100:Oxygen / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D013552:Swine; D014230:Triazoles / Q000494:pharmacology; D014363:Tryptamines; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use
D007211:Indoles; D010880:Piperidines; D014230:Triazoles; D014363:Tryptamines; D014662:Vasoconstrictor Agents; C093622:rizatriptan; D018170:Sumatriptan; C106783:naratriptan; D010100:Oxygen