title: Enantioselective actions of 4-amino-3-hydroxybutanoic acid and (3-amino-2-hydroxypropyl)methylphosphinic acid at recombinant GABA(C) receptors.
abstract: The R- and S-enantiomers of 4-amino-3-hydroxybutanoic acid (GABOB) were full agonists at human recombinant rho1 GABA(C) receptors. Their enantioselectivity (R>S) matched that reported for their agonist actions at GABA(B) receptors, but was the opposite to that reported at GABA(A) receptors (S>R). The corresponding methylphosphinic acid analogues proved to be rho1 GABA(C) receptor antagonists with R(+)-CGP44533 being more potent than S(-)-CGP44532, thus showing the opposite enantioselectivity to the agonists R(-)- and S(+)-GABOB. These studies highlight the different stereochemical requirements for the hydroxy group in these analogues at GABA(A), GABA(B) and GABA(C) receptors.
authors.affiliation: The Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, The University of Sydney, NSW 2006, Australia.
authors.forename: Tina
authors.initials: T
authors.lastname: Hinton
authors.forename: Mary
authors.initials: M
authors.lastname: Chebib
authors.forename: Graham A R
authors.initials: GA
authors.lastname: Johnston
mesh_terms: D000818:Animals; D018755:GABA Agonists / Q000737:chemistry / Q000494:pharmacology*; D018756:GABA Antagonists / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D010721:Phosphinic Acids / Q000737:chemistry / Q000494:pharmacology; D018079:Receptors, GABA / Q000737:chemistry / Q000187:drug effects*; D018080:Receptors, GABA-B / Q000737:chemistry*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014981:Xenopus; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C112036:3-amino-2-(S)-hydroxypropyl-methyl-phosphinic acid; D018755:GABA Agonists; D018756:GABA Antagonists; C087200:GABA-C receptor; D010721:Phosphinic Acids; D018079:Receptors, GABA; D018080:Receptors, GABA-B; D011994:Recombinant Proteins; C004480:4-amino-3-hydroxybutyric acid; D005680:gamma-Aminobutyric Acid