New insights in insurmountable antagonism
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...
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Published in: | Fundamental & clinical pharmacology Vol. 16; no. 4; pp. 263 - 272 |
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Main Authors: | , , , |
Format: | Journal Article |
Language: | English |
Published: |
Oxford, UK
Blackwell Science, Ltd
01-08-2002
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Subjects: | |
Online Access: | Get full text |
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Summary: | 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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Bibliography: | ArticleID:095 istex:D81E033F55C149CB57E4F63A0AA67E8DE56EDF54 ark:/67375/WNG-LGSFZTTZ-S ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 |
ISSN: | 0767-3981 1472-8206 |
DOI: | 10.1046/j.1472-8206.2002.00095.x |