GABA-A receptor subtypes in the brain: a paradigm for CNS drug discovery?

被引：243

作者：

Whiting, PJ ^{[1
]}

机构：

[1] Merck Sharp & Dohme Ltd, Res Labs, Ctr Res Neurosci, Harlow CM20 2QR, Essex, England

来源：

DRUG DISCOVERY TODAY | 2003年 / 8卷 / 10期

关键词：

D O I：

10.1016/S1359-6446(03)02703-X

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The clinical importance of benzodiazepines, barbiturates and general anesthetics, all of which act through the gamma-aminobutyric acid (GABA)-A neurotransmitter receptor, is testament to its significance as a CNS drug target. These drugs were all developed before there was any understanding of the diversity of this receptor gene family. Recent studies using genetically modified mice and GABA-A receptor-subtype-selective compounds have helped to delineate the function of some of these subtypes, and have revealed that it might be possible to develop a new generation of selective drugs with improved profiles or novel applications.

引用

页码：445 / 450

页数：6

共 41 条

[1]

Barnard EA, 1998, PHARMACOL REV, V50, P291

[2] The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid [J].

Belelli, D ;

Lambert, JJ ;

Peters, JA ;

Wafford, K ;

Whiting, PJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :11031-11036

[3] Pharmacological characterization of a novel cell line expressing human α4β3δ GABAA receptors [J].

Brown, N ;

Kerby, J ;

Bonnert, TP ;

Whiting, PJ ;

Wafford, KA .

BRITISH JOURNAL OF PHARMACOLOGY, 2002, 136 (07) :965-974

[4] The human hippocampus and spatial and episodic memory [J].

Burgess, N ;

Maguire, EA ;

O'Keefe, J .

NEURON, 2002, 35 (04) :625-641

[5]

Chapouthier Georges, 2002, Current Topics in Medicinal Chemistry, V2, P841, DOI 10.2174/1568026023393552

[6]

Collinson N, 2002, J NEUROSCI, V22, P5572

[7] Mechanism of action of the hypnotic zolpidem in vivo [J].

Crestani, F ;

Martin, JR ;

Möhler, H ;

Rudolph, U .

BRITISH JOURNAL OF PHARMACOLOGY, 2000, 131 (07) :1251-1254

[8] Trace fear conditioning involves hippocampal α5 GABAA receptors [J].

Crestani, F ;

Keist, R ;

Fritschy, JM ;

Benke, D ;

Vogt, K ;

Prut, L ;

Blüthmann, H ;

Möhler, H ;

Rudolph, U .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (13) :8980-8985

[9]

Davis KL, 2002, NEUROPSYCHOPHARMACOL

[10] GABA(A)-RECEPTOR HETEROGENEITY IN THE ADULT-RAT BRAIN - DIFFERENTIAL REGIONAL AND CELLULAR-DISTRIBUTION OF 7 MAJOR SUBUNITS [J].

FRITSCHY, JM ;

MOHLER, H .

JOURNAL OF COMPARATIVE NEUROLOGY, 1995, 359 (01) :154-194

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