Bioisosteric determinants for subtype selectivity of ligands for heteromeric GABAA receptors

被引：19

作者：

Ebert, B

Mortensen, M

Thompson, SA

Kehler, J

Wafford, KA

Krogsgaard-Larsen, P

机构：

[1] Royal Danish Sch Pharm, Dept Pharmacol, Ctr Drug Design & Transport, DK-2100 Copenhagen, Denmark

[2] Royal Danish Sch Pharm, Dept Med Chem, Ctr Drug Design & Transport, DK-2100 Copenhagen, Denmark

[3] Merck Sharp & Dohme Ltd, Res Labs, Dept Pharmacol, Harlow CM20 2QR, Essex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(01)00184-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1573 / 1577

页数：5

共 25 条

[1]

Barnard EA, 1998, PHARMACOL REV, V50, P291

[2] θ, a novel γ-aminobutyric acid type A receptor subunit [J].