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Potent, selective tetrahydro-beta-carboline antagonists of the serotonin 2B (5HT2B) contractile receptor in the rat stomach fundus.
- Source :
-
Journal of medicinal chemistry [J Med Chem] 1996 Jul 05; Vol. 39 (14), pp. 2773-80. - Publication Year :
- 1996
-
Abstract
- A series of potent, selective 5HT2B receptor antagonists has been identified based upon yohimbine, with SAR studies resulting in a 1000-fold increase in 5HT2B receptor affinity relative to the starting structure (-log KBS > 10.0 have been obtained). These high-affinity tetrahydro-beta-carboline antagonists are able to discriminate among the 5HT2 family of serotonin receptors, with members of the series showing selectivities of more than 100-fold versus both the 5HT2A and 5HT2C receptors based upon radioligand binding and functional assays. As the first compounds reported with such selectivity and enhanced receptor affinity, these tetrahydro-beta-carboline antagonists are useful tools for elucidating the role of serotonin acting at the 5HT2B receptor in normal and disease physiology.
- Subjects :
- Animals
Carbolines chemical synthesis
Cell Line
Cricetinae
Gastric Fundus
In Vitro Techniques
Male
Mesocricetus
Mice
Molecular Structure
Muscle Contraction drug effects
Rats
Rats, Wistar
Receptor, Serotonin, 5-HT2A
Receptor, Serotonin, 5-HT2B
Receptor, Serotonin, 5-HT2C
Receptors, Serotonin genetics
Receptors, Serotonin metabolism
Serotonin Antagonists chemical synthesis
Structure-Activity Relationship
Yohimbine chemistry
Carbolines pharmacology
Muscle, Smooth drug effects
Receptors, Serotonin drug effects
Serotonin Antagonists pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-2623
- Volume :
- 39
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 8709108
- Full Text :
- https://doi.org/10.1021/jm960062t