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Histamine H1 receptor antagonism by cetirizine in isolated guinea pig tissues: influence of receptor reserve and dissociation kinetics.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2003 May 30; Vol. 470 (1-2), pp. 87-94. - Publication Year :
- 2003
-
Abstract
- We characterised histamine H(1) receptor antagonism by cetirizine and its enantiomers on isolated guinea pig ileum and trachea. Competitive or mixed (competitive and apparent noncompetitive) antagonism profiles were observed. The order of potency was: chlorpheniramine> or =mepyramine>levocetirizine>cetirizine> or =terfenadine>loratadine>dextrocetirizine. The inhibitory effects of cetirizine, levocetirizine, terfenadine and loratadine were slowly reversible compared to those of dextrocetirizine or mepyramine. Cetirizine and its enantiomers were inactive on L-type Ca(2+) channels. Reduction of the histamine H(1) receptor reserve by dibenamine in the ileum (100-fold higher than in the trachea) showed a gradual change from the competitive profile of dextrocetirizine and mepyramine to a mixed profile. The present results show that cetirizine and levocetirizine are selective competitive but slowly reversible histamine H(1) receptor antagonists. Their mixed antagonism profile observed in the trachea can be explained by the small receptor reserve present in this tissue compared to the ileum and their very slow dissociation rate from the histamine H(1) receptor.
- Subjects :
- Animals
Aorta drug effects
Aorta metabolism
Dose-Response Relationship, Drug
Guinea Pigs
Histamine metabolism
Histamine pharmacology
Histamine H1 Antagonists metabolism
Ileum metabolism
In Vitro Techniques
Male
Rats
Trachea metabolism
Cetirizine pharmacology
Histamine H1 Antagonists pharmacology
Ileum drug effects
Receptors, Histamine H1 metabolism
Trachea drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 470
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12787835
- Full Text :
- https://doi.org/10.1016/s0014-2999(03)01781-3