Role of 5-HT1-like receptors in the reduction of porcine cranial arteriovenous anastomotic shunting by sumatriptan.
1. The new tryptamine derivative sumatriptan (GR43175) is effective in the treatment of migraine. Since several antimigraine agents reduce cranial arteriovenous anastomotic blood flow in the anaesthetized pig, we have investigated the carotid haemodynamic effects of sumatriptan. 2. Sumatriptan (10, 30, 100 and 300 micrograms kg-1, i.v.) reduced total common carotid blood flow, exclusively by affecting its arteriovenous anastomotic fraction; the capillary fraction even increased with the highest doses. 3. These reductions in the carotid arteriovenous anastomotic ('shunt') blood flow were mediated by a 5-HT1-like receptor, as methiothepin, but not ketanserin, antagonized the responses to sumatriptan. 4. Sumatriptan increased the difference in oxygen saturation between arterial and jugular venous blood, which is likely to be a consequence of the reduction of the carotid shunt blood flow. 5. The selective reduction in arteriovenous anastomotic blood flow produced by sumatriptan may reflect its antimigraine action, thought to involve vasoconstriction of those cranial vessels, be they 'shunt' vessels or not, which are distended and inflamed during a migraine attack.
den Boer
M O
MO
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands.
Villalón
C M
CM
Heiligers
J P
JP
Humphrey
P P
PP
Saxena
P R
PR
D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects / Q000502:physiology; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004878:Ergotamine / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007211:Indoles / Q000494:pharmacology*; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*; D018170:Sumatriptan; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007211:Indoles; D011985:Receptors, Serotonin; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D018170:Sumatriptan; D004878:Ergotamine