Enantioselective actions of 4-amino-3-hydroxybutanoic acid and (3-amino-2-hydroxypropyl)methylphosphinic acid at recombinant GABA(C) receptors

Bioorg Med Chem Lett. 2008 Jan 1;18(1):402-4. doi: 10.1016/j.bmcl.2007.10.019. Epub 2007 Oct 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GABA Agonists / chemistry
  • GABA Agonists / pharmacology*
  • GABA Antagonists / chemistry
  • GABA Antagonists / pharmacology
  • Humans
  • Hydrogen Bonding
  • Phosphinic Acids / chemistry
  • Phosphinic Acids / pharmacology
  • Receptors, GABA / chemistry
  • Receptors, GABA / drug effects*
  • Receptors, GABA-B / chemistry*
  • Recombinant Proteins / antagonists & inhibitors
  • Stereoisomerism
  • Structure-Activity Relationship
  • Substrate Specificity
  • Xenopus
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / chemistry
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • 3-amino-2-(S)-hydroxypropyl-methyl-phosphinic acid
  • GABA Agonists
  • GABA Antagonists
  • GABA-C receptor
  • Phosphinic Acids
  • Receptors, GABA
  • Receptors, GABA-B
  • Recombinant Proteins
  • 4-amino-3-hydroxybutyric acid
  • gamma-Aminobutyric Acid