Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect
(2005) In Clinical Science 109(3). p.335-342- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/223454
- author
- Edvinsson, Lars LU ; Uddman, Erik LU ; Wackenfors, Angelica LU ; Davenport, A ; Longmore, J and Malmsjö, Malin LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- plasma concentration, 5-HT (5-hydroxytryptamine) receptor, cerebral artery, coronary artery, smooth muscle, triptan, in vitro pharmacology
- in
- Clinical Science
- volume
- 109
- issue
- 3
- pages
- 335 - 342
- publisher
- Portland Press
- external identifiers
-
- pmid:15853772
- wos:000232126900014
- scopus:25144453767
- ISSN
- 1470-8736
- DOI
- 10.1042/CS20050016
- language
- English
- LU publication?
- yes
- id
- 50bc8cc6-b445-443e-b52f-1291276b5faf (old id 223454)
- date added to LUP
- 2016-04-01 11:50:12
- date last changed
- 2024-02-23 09:35:43
@article{50bc8cc6-b445-443e-b52f-1291276b5faf,
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.}},
author = {{Edvinsson, Lars and Uddman, Erik and Wackenfors, Angelica and Davenport, A and Longmore, J and Malmsjö, Malin}},
issn = {{1470-8736}},
keywords = {{plasma concentration; 5-HT (5-hydroxytryptamine) receptor; cerebral artery; coronary artery; smooth muscle; triptan; in vitro pharmacology}},
language = {{eng}},
number = {{3}},
pages = {{335--342}},
publisher = {{Portland Press}},
series = {{Clinical Science}},
title = {{Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect}},
url = {{http://dx.doi.org/10.1042/CS20050016}},
doi = {{10.1042/CS20050016}},
volume = {{109}},
year = {{2005}},
}