Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect.

Content Provider	Semantic Scholar
Author	Edvinsson, Lars Uddman, Erik Wackenfors, Angelica Davenport, Anthony P. Longmore, Jenny Malmsjö, Malin
Copyright Year	2005
Abstract	Triptans are agonists at 5-HT1B and 5-HT1D (where 5-HT is 5-hydroxytryptamine; serotonin) receptors and cause vasoconstriction of isolated blood vessels. The aim of the present study was to determine vasoconstrictor potency (EC50) of triptans in human coronary and cerebral arteries and to examine whether there was any relationship with the maximal plasma concentrations (Cmax; nM) of the drugs achieved following oral administration of clinically relevant doses to man using values reported in the literature. We also examined the expression of 5-HT1B receptors in atherosclerotic and normal coronary arteries. The vasocontractile responses to sumatriptan, rizatriptan or eletriptan were characterized by in vitro pharmacology. The ratio of Cmax/EC50 was calculated. 5-HT1B and 5-HT1D receptors were visualized by immunohistochemical techniques in coronary arteries. Sumatriptan, rizatriptan and eletriptan were powerful vasoconstrictors in cerebral artery. The rank order of agonist potency was eletriptan=rizatriptan=sumatriptan. In the coronary artery, the triptans were weaker vasoconstrictors. The rank order of potency was similar. In cerebral artery the ratio of Cmax/EC50 was not significantly different from unity, indicating a relationship between these two parameters. In general for the coronary artery, the ratios were significantly less than unity, indicating no direct relationship. Immunohistochemistry showed expression of 5-HT1B receptors in the medial layer, but did not reveal any obvious difference in 5-HT1B receptor expression between normal and atherosclerotic coronary arteries. The results support the notion that triptans are selective vasoconstrictors of cerebral arteries over coronary arteries and that there is a relationship between vasoconstrictor potency in cerebral arteries and clinically relevant plasma levels.
Starting Page	1161
Ending Page	1165
Page Count	5
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://www.clinsci.org/content/ppclinsci/109/3/335.full.pdf
PubMed reference number	15853772v1
Volume Number	109
Issue Number	3
Journal	Clinical science
Language	English
Access Restriction	Open
Subject Keyword	Administration, Oral Arterial system Arteries Atherosclerosis Blood Vessel Cmax Coronary Artery Disease In Vitro [Publication Type] Pharmacology Receptor, Serotonin, 5-HT1B Serotonin Structure of cerebral artery Sumatriptan Triptans Vascular constriction (function) Vasoconstrictor Agents eletriptan rizatriptan
Content Type	Text
Resource Type	Article