Received for publication May 31, 2005.
Revised July 15, 2005.
Accepted for publication July 15, 2005.

Donitriptan decreases jugular venous oxygen saturation in rats in the absence of cranial vasoconstriction: An overlooked mechanism of antimigraine action?

Abstract

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 are dependent or not of cranial vasoconstrictor. In the present study, vehicle (n=10), donitriptan (2.5, 10 and 40 µg/kg, n=8) or sumatriptan (630 µg/kg, n=8) were infused into the carotid artery in the anesthetized rat. Regional blood flows were evaluated in the presence of donitriptan (10 µg/kg, n=6) or vehicle (n=6). Jugular venous oxygen saturation was significantly decreased by donitriptan (from 10 µg/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 % (P<0.05 vs. vehicle). Similarly, sumatriptan significantly decreased venous oxygen saturation and increased jugular carbon dioxide partial pressure. These changes induced by donitriptan are abolished by a 5-HT_1B/1D receptor antagonist (GR 127935). In addition, donitriptan failed to significantly affect systemic arterial pressure or 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.

Key words: 5-HT1B/1D receptors, donitriptan, migraine, regional blood flow, sumatriptan, venous oxygen saturation