Document Detail


Phosphinic, phosphonic and seleninic acid bioisosteres of isonipecotic acid as novel and selective GABA(C) receptor antagonists.
MedLine Citation:
PMID:  12590939     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A number of amino acids bioisosterically derived from the specific GABA(A) agonist, isonipecotic acid, were electrophysiologically characterized as antagonists at GABA(C) rho(1) receptors expressed in Xenopus oocytes. The phosphinic acid analogue of isonipecotic acid, piperidin-4-ylphosphinic acid (2), was comparable with the standard GABA(C) antagonist, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), in terms of potency and GABA(C) versus GABA(A) receptor selectivity. Whereas the phosphonic acid analogue, piperidin-4-ylphosphonic acid (4), was at least an order of magnitude weaker than piperidin-4-ylphosphinic acid as a GABA(C) antagonist, the seleninic acid analogue, piperidin-4-ylseleninic acid (SEPI, 6), was the most potent and selective GABA(C) antagonist within the group of isonipecotic acid derived amino acids studied.
Authors:
Dorte Krehan; Bente Frølund; Povl Krogsgaard-Larsen; Jan Kehler; Graham A R Johnston; Mary Chebib
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Neurochemistry international     Volume:  42     ISSN:  0197-0186     ISO Abbreviation:  Neurochem. Int.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-02-19     Completed Date:  2003-05-01     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  561-5     Citation Subset:  IM    
Affiliation:
Centre for Drug Design and Transport, Department of Medicinal Chemistry, The Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carboxylic Acids / chemistry,  pharmacology*
Female
GABA Antagonists / pharmacology*
Humans
Isonipecotic Acids / chemistry*
Oocytes
Organoselenium Compounds / chemistry,  pharmacology*
Phosphinic Acids / chemistry,  pharmacology*
Phosphonic Acids / chemistry,  pharmacology*
Protein Isoforms / drug effects
Receptors, GABA / drug effects*
Xenopus laevis
Chemical
Reg. No./Substance:
0/Carboxylic Acids; 0/GABA Antagonists; 0/GABA-C receptor; 0/Isonipecotic Acids; 0/Organoselenium Compounds; 0/Phosphinic Acids; 0/Phosphonic Acids; 0/Protein Isoforms; 0/Receptors, GABA; 0/seleninic acid

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


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