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 ϭ 10), donitriptan (2.5, 10, and 40 g/kg; n ϭ 8) or sumatriptan (630 g/kg; n ϭ 8) were infused into the carotid artery in the anesthetized rat. Regional blood flows were evaluated in the presence of donitriptan (10 g/kg; n ϭ 6) or vehicle (n ϭ 6). Jugular venous oxygen saturation was significantly decreased by donitriptan (from 10 g/kg) with maximal changes of Ϫ32.9 Ϯ 8.0%. Jugular carbon dioxide partial pressure was increased by donitriptan, reaching maximal changes of 17.7 Ϯ 4.6% (P Ͻ 0.05 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. 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 current mechanism(s) of action of 5-HT 1B/1D receptor agonists (triptans) in the acute relief of migraine headache is considered to comprise cranial vasoconstriction (Humphrey and Feniuk, 1991), peripheral neuronal inhibition (Moskowitz, 1992), and inhibition of transmission through secondorder neurons of the trigeminocervical complex (Hoskin et al., 1996), leading to inhibition of the effects of activated nociceptive terminal afferents (Goadsby, 2000). Donitriptan, which has been evaluated for efficacy in the acute relief of migraine headache in phase II clinical trials (Dukat, 2001), and other triptans (Létienne et al., 2003a) augmented cerebral oxygen utilization and tissue metabolism. This additional mechanism of action may also be relevant to the acute headache-relieving effects of triptans as a whole. However, our previous studies in the anesthetized pig (Létienne et al., 2003a,b) showed that the triptans increased arteriovenous oxygen saturation difference and carbon dioxide partial pressure in venous blood draining the head but also produced concomitant carotid vasoconstriction. Consequently, it was not possible to determine whether these events occurred independently.The aim of the present investigation was therefore to determine whether donitriptan and sumatriptan produced similar effects on jugular venous blood gas parameters in a model in which triptans are considered not to produce cranial vasoconstriction. Thus, the study was performed in anestheArticle, publication date, and citation information can be found at