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The aim of the present study was to determine whether donitriptan and sumatriptan decreased jugular venous oxygen saturation and increased carbon dioxide partial pressure in venous blood. However, previous studies conducted with these compounds cannot discriminate whether the decrease of venous oxygen saturation is dependent of cranial vasoconstrictor. In the present study, vehicle (n = 10), donitriptan (2.5, 10, and 40 microg/kg; n = 8) or sumatriptan (630 microg/kg; n = 8) were infused into the carotid artery in the anesthetized rat. Regional blood flows were evaluated in the presence of donitriptan (10 microg/kg; n = 6) or vehicle (n = 6). Jugular venous oxygen saturation was significantly decreased by donitriptan (from 10 microg/kg) with maximal changes of -32.9 +/- 8.0%. Jugular carbon dioxide partial pressure was increased by donitriptan, reaching maximal changes of 17.7 +/- 4.6% (P0.05 versus vehicle). Similarly, sumatriptan significantly decreased venous oxygen saturation and increased jugular carbon dioxide partial pressure. These changes induced by donitriptan are abolished by the 5-hydroxytryptamine (5-HT)(1B/1D) receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2-[-methyl-4(5-methyl-1,2,4)-oxadiazol-3-yl]-(1,1 biphenyl)-4-carboxamide dihydrochloride). In addition, donitriptan was devoid of significant effects on systemic arterial pressure, heart rate, or regional blood flows, including systemic arterial-jugular venous anastomotic, systemic, or cranial. The results demonstrate that donitriptan increases cerebral oxygen consumption by 5-HT(1B/1D) receptor activation in the absence of cranial vasoconstriction.

The effects of donitriptan on systemic arterial-jugular venous oxygen saturation difference were evaluated in pentobarbitone-anesthetized pigs. 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 (40% polyethyleneglycol in saline, n = 9) or donitriptan (0.01, 0.04, 0.16, 0.63, 2.5, 10, and 40 microg/kg, n = 7) were cumulatively infused over 15 min/dose. The involvement of 5-hydroxytryptamine(1B) (5-HT(1B)) receptors was assessed in the presence of the 5-HT(1B/1D) receptor antagonist, GR 127935. Donitriptan decreased markedly and dose dependently jugular venous oxygen saturation [ED(50) 0.5 (0.3-1.1) microg/kg], in parallel with increases in carotid vascular resistance [ED(50) 0.9 (0.7-1.1) microg/kg]. Since arterial oxygen saturation and partial pressure remained unchanged, donitriptan significantly increased arteriovenous oxygen saturation difference from 0.63 microg/kg (maximal variation: 57 +/- 18%, P0.05 compared with vehicle). Unexpectedly, donitriptan from 2.5 microg/kg induced marked and significant increases in carbon dioxide partial pressure (pVCO(2)) in venous blood (maximal increase 18.8 +/- 5.7%; P0.05 compared with vehicle). Pretreatment with GR 127935 (0.63 mg/kg, n = 5) abolished the fall in venous oxygen saturation and the increase in carotid vascular resistance and reduced the increases in pVCO(2) induced by donitriptan. The results demonstrate that donitriptan, via 5-HT(1B) receptor activation, decreases the oxygen saturation of venous blood draining the head, concomitantly with cranial vasoconstriction. Since donitriptan also increased pVCO(2), an effect upon cerebral oxygen consumption and metabolism is suggested in addition to cranial vasoconstriction, which may be relevant to its headache-relieving effects.