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 is dependent 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 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-HT1B/1D receptor activation in the absence of cranial vasoconstriction.
Footnotes
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.090159.
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ABBREVIATIONS: 5-HT 5-hydroxytryptamine; 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; AVA, arteriovenous anastomosis; donitriptan, 4-[4-[2-[3-(2 amino-ethyl)-1H-indol-5-yloxy]-acetyl]-piperazin-1-yl]-benzonitrile hydrochloride; MAP, mean arterial pressure; HR, heart rate; CaBF, carotid blood flow; CaVR, carotid vascular resistance; ANOVA, analysis of variance; PaO2, oxygen partial pressure in arterial blood; PaCO2, carbon dioxide partial pressure in arterial blood; AOS, oxygen saturation in systemic arterial blood; VOS, jugular venous oxygen saturation; AVOSD, arterial-jugular venous oxygen saturation difference; PvO2, oxygen partial pressure in venous blood; PvCO2, carbon dioxide partial pressure in venous blood; SB 224289, 1′-methyl-5-(2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4;carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4′-piperidine]; BRL 15572, 3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol.HCL.
- Received May 27, 2005.
- Accepted July 15, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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Donitriptan Decreases Jugular Venous Oxygen Saturation in Rats in the Absence of Cranial Vasoconstriction: An Overlooked Mechanism of Antimigraine Action?
