| Ibotenic acid and thioibotenic acid: a remarkable difference in activity at group III metabotropic glutamate receptors. | |
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MedLine Citation:
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PMID: 14985045 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In this study, we have determined and compared the pharmacological profiles of ibotenic acid and its isothiazole analogue thioibotenic acid at native rat ionotropic glutamate (iGlu) receptors and at recombinant rat metabotropic glutamate (mGlu) receptors expressed in mammalian cell lines. Thioibotenic acid has a distinct pharmacological profile at group III mGlu receptors compared with the closely structurally related ibotenic acid; the former is a potent (low microm) agonist, whereas the latter is inactive. By comparing the conformational energy profiles of ibotenic and thioibotenic acid with the conformations preferred by the ligands upon docking to mGlu1 and models of the other mGlu subtypes, we propose that unlike other subtypes, group III mGlu receptor binding sites require a ligand conformation at an energy level which is prohibitively expensive for ibotenic acid, but not for thioibotenic acid. These studies demonstrate how subtle differences in chemical structures can result in profound differences in pharmacological activity. |
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Authors:
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Mette B Hermit; Jeremy R Greenwood; Birgitte Nielsen; Lennart Bunch; Charlotte G Jørgensen; Henrik T Vestergaard; Tine B Stensbøl; Connie Sanchez; Povl Krogsgaard-Larsen; Ulf Madsen; Hans Bräuner-Osborne |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of pharmacology Volume: 486 ISSN: 0014-2999 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2004 Feb |
Date Detail:
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Created Date: 2004-02-26 Completed Date: 2005-01-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 241-50 Citation Subset: IM |
Affiliation:
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Department of Medicinal Chemistry, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, Copenhagen, DK-2100, Denmark. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals CHO Cells Cricetinae Cricetulus Excitatory Amino Acid Agonists / chemistry, pharmacology* Ibotenic Acid / chemistry, pharmacology* Ligands Male Mice Models, Molecular Molecular Conformation Radioligand Assay Rats Receptors, Metabotropic Glutamate / agonists*, classification, physiology Thiazoles / chemistry, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Excitatory Amino Acid Agonists; 0/Ligands; 0/Receptors, Metabotropic Glutamate; 0/Thiazoles; 0/thioibotenic acid; 2552-55-8/Ibotenic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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