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

The R- and S-enantiomers of 4-amino-3-hydroxybutanoic acid (GABOB) were full agonists at human recombinant ρ1 GABAC receptors. Their enantioselectivity (R > S) matched that reported for their agonist actions at GABAB receptors, but was the opposite to that reported at GABAA receptors (S > R). The corresponding methylphosphinic acid analogues proved to be ρ1 GABAC 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 GABAA, GABAB and GABAC receptors.