Cranial vascular effects of zolmitriptan, a centrally active 5-HT1B/1D receptor partial agonist for the acute treatment of migraine

Abstract The anti-migraine drug zolmitriptan is a novel 5-HT 1B/1D receptor partial agonist which, unlike sumatriptan, has been shown to cross the intact blood–brain barrier. In this study we examined whether or not the ability to access the cerebro-vascular intima affects the way in which a centrally-active 5-HT 1B/1D receptor agonist influences cranial haemodynamics. The effects of zolmitriptan on carotid arterial blood flow distribution were studied in anaesthetised cats using radiolabelled microspheres. Zolmitriptan (10–1000 μg kg −1 i.v.) selectively reduced arteriovenous–anastomotic (AVA) conductance producing a maximum decrease of 92.5±2.3%. The drug also produced a modest reduction in extra-cerebral conductance (23.9±6.5% maximum reduction at 30 μg kg −1 , i.v.), but was without effect on cerebral conductance. Using laser doppler flowmetry in anaesthetised cats, zolmitriptan (1–30 μg kg −1 , i.v.) produced dose-dependent decreases in ear microvascular conductance (15±5 to 60±6%) which mirrored decreases in carotid arterial conductance (12±11 to 61±5%). By contrast, zolmitriptan at doses up to 1000 μg kg −1 was without effect on cerebral microvascular conductance. Although zolmitriptan crosses the blood–brain barrier and can therefore access the cerebro-vascular intima, this study suggests that this property does not adversely affect cerebrovascular function.