| New insights in insurmountable antagonism. | |
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MedLine Citation:
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PMID: 12570014 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Antagonists that produce parallel rightward shifts of agonist dose-response curves with no alteration of the maximal response are traditionally classified as surmountable, while insurmountable antagonists also depress the maximal response. Although the longevity of the antagonist-receptor complex is quoted in many studies to explain insurmountable antagonism, slowly interconverting receptor conformations, allosteric binding sites, and receptor internalization have been evoked as alternative explanations. To complicate matters even further, insurmountable antagonism is not only drug-related; it may also depend on the tissue, species and experimental design. For the sake of drug development, it is important to elucidate the molecular mechanisms of insurmountable antagonism. New experimental approaches, such as intact cell studies and the use of computer-assisted simulations based on dynamic receptor models, herald the advent of better insight in the future. |
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Authors:
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G Vauquelin; I Van Liefde; B B Birzbier; P M L Vanderheyden |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Fundamental & clinical pharmacology Volume: 16 ISSN: 0767-3981 ISO Abbreviation: Fundam Clin Pharmacol Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2003-02-06 Completed Date: 2003-04-10 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8710411 Medline TA: Fundam Clin Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 263-72 Citation Subset: IM |
Affiliation:
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Department of Molecular and Biochemical Pharmacology, Free University of Brussels (VUB), Sint-Genesius Rode, Belgium. gvauquel@vub.ac.be |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Allosteric Regulation Binding, Competitive Computer Simulation Humans Models, Biological* Receptors, Cell Surface / agonists, antagonists & inhibitors*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Cell Surface |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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