QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.105.090159v1 315/2/849    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Létienne, R. Articles by Le Grand, B. Search for Related Content PubMed PubMed Citation Articles by Létienne, R. Articles by Le Grand, B.

CARDIOVASCULAR

Donitriptan Decreases Jugular Venous Oxygen Saturation in Rats in the Absence of Cranial Vasoconstriction: An Overlooked Mechanism of Antimigraine Action?

Centre de Recherche Pierre Fabre, Castres Cedex, France

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-HT_1B/1D receptor activation in the absence of cranial vasoconstriction.

Address correspondence to: Dr. Robert Létienne, Centre de Recherche Pierre Fabre, 17, avenue Jean Moulin, 81106 Castres Cedex, France. E-mail: robert.letienne{at}pierre-fabre.com