Bioisosteric determinants for subtype selectivity of ligands for heteromeric GABA(A) receptors.
The potency and efficacy of a series of bioisosterically modified GABA analogues were determined electrophysiologically using heteromeric GABA(A) receptors expressed in Xenopus oocytes. These agonist parameters were shown to be strongly dependent on the receptor subunit combination. On the other hand, the antagonist potencies of the classical GABA(A) antagonists SR 95531 (7) and BMC (8) and also of 5g and the phosphinic acid bioisosteres of 5a, compounds 5f and 6, were essentially independent of the receptor subunit combinations.
Ebert
B
B
The Centre for Drug Design and Transport, Departments of Pharmacology and Medicinal Chemistry, The Royal Danish School of Pharmacy, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
Mortensen
M
M
Thompson
S A
SA
Kehler
J
J
Wafford
K A
KA
Krogsgaard-Larsen
P
P
D000818:Animals; D018755:GABA Agonists / Q000378:metabolism; D018756:GABA Antagonists / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009865:Oocytes; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection; D014981:Xenopus
D018755:GABA Agonists; D018756:GABA Antagonists; D008024:Ligands; D021122:Protein Subunits; D011963:Receptors, GABA-A