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CARDIOVASCULAR

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

Centre de Recherche Pierre Fabre, Castres, France

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 µg/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 µg/kg, respectively) concomitantly with increases in carotid vascular resistance. Rizatriptan significantly and dose dependently, from 160 µg/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 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.

Address correspondence to: Dr. G. W. John, Centre de Recherche Pierre Fabre, 17, avenue Jean Moulin, 81106 Castres Cedex, France. E-mail: gareth.john{at}pierre-fabre.com

This article has been cited by other articles:

				R. Letienne, J.-C. Blanchet, E. Sole, G. W. John, and B. Le Grand Donitriptan Decreases Jugular Venous Oxygen Saturation in Rats in the Absence of Cranial Vasoconstriction: An Overlooked Mechanism of Antimigraine Action? J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 849 - 857. [Abstract] [Full Text] [PDF]