Bioisosteric determinants for subtype selectivity of ligands for heteromeric GABA(A) receptors

B Ebert; M Mortensen; S A Thompson; J Kehler; K A Wafford; P Krogsgaard-Larsen

doi:10.1016/s0960-894x(01)00184-6

Bioisosteric determinants for subtype selectivity of ligands for heteromeric GABA(A) receptors

Bioorg Med Chem Lett. 2001 Jun 18;11(12):1573-7. doi: 10.1016/s0960-894x(01)00184-6.

Authors

B Ebert¹, M Mortensen, S A Thompson, J Kehler, K A Wafford, P Krogsgaard-Larsen

Affiliation

¹ 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.

PMID: 11412984
DOI: 10.1016/s0960-894x(01)00184-6

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
GABA Agonists / metabolism
GABA Antagonists / metabolism
Humans
Inhibitory Concentration 50
Ligands
Oocytes
Protein Subunits
Receptors, GABA-A / chemistry*
Receptors, GABA-A / metabolism*
Transfection
Xenopus

Substances

GABA Agonists
GABA Antagonists
Ligands
Protein Subunits
Receptors, GABA-A