Document Detail

I(1) imidazoline receptors involved in cardiovascular regulation: where are we and where are we going?
MedLine Citation:
PMID:  15028592     Owner:  NLM     Status:  MEDLINE    
Clonidine-like drugs (hybrid drugs) reduce blood pressure by acting centrally at both alpha(2)-adrenergic receptors (alpha(2)AR) and I(1) receptors (I(1)R). Some attempts at cloning I(1)R have failed, probably because of the lack of selectivity of the ligands. Recently, compounds acting exclusively at I(1)R were synthesized: LNP 911, LNP509, and S23515. For example, LNP911 has a K(d) value of 1.7 nmol/L at I(1)R. LNP509 and S23515 reduce blood pressure when injected centrally in anesthetized animals, whereas S23757 behaves as an antagonist of hypotensive imidazolines. LNP509 reduces blood pressure even in genetically engineered mice lacking functional alpha(2)AR. An exclusive action at central I(1)R is therefore sufficient to modify blood pressure. With the help of drugs selective for I(1)R and alpha-methylnoradrenaline, selective for alpha(2)AR, we showed that imidazoline and alpha(2)-adrenergic mechanisms interact synergistically in controlling the blood pressure. Such a synergism may explain the very powerful hypotensive effects of hybrid drugs. The new ligands selective for I(1)R will be very helpful to investigate the molecular features and the signaling system of I(1)R.
P Bousquet; H Greney; V Bruban; S Schann; J D Ehrhardt; L Monassier; J Feldman
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Annals of the New York Academy of Sciences     Volume:  1009     ISSN:  0077-8923     ISO Abbreviation:  Ann. N. Y. Acad. Sci.     Publication Date:  2003 Dec 
Date Detail:
Created Date:  2004-03-18     Completed Date:  2004-04-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7506858     Medline TA:  Ann N Y Acad Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  228-33     Citation Subset:  IM    
INSERM E0333, Faculté de Médecine, Université Louis Pasteur, 67000 Strasbourg, France.
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MeSH Terms
Antihypertensive Agents / metabolism
Blood Pressure / physiology*
Cardiovascular Physiological Phenomena*
Cyclopropanes / metabolism
Imidazoline Receptors
Oxazoles / metabolism
Protein Isoforms / metabolism
Pyrroles / metabolism
Pyrrolidines / metabolism
Receptors, Drug / metabolism*
Reg. No./Substance:
0/2-(2-chloro-4-iodophenylamino)-5-methylpyrroline; 0/5-(2-bnromophenoxy)methyl-2-amino-4,5-dihydro-1,3-oxazole; 0/Antihypertensive Agents; 0/Cyclopropanes; 0/Imidazoline Receptors; 0/LNP 509; 0/Ligands; 0/Oxazoles; 0/Protein Isoforms; 0/Pyrroles; 0/Pyrrolidines; 0/Receptors, Drug

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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