GABAA receptor subtypes:: dissecting their pharmacological functions

被引:355
作者
Rudolph, U [1 ]
Crestani, F [1 ]
Möhler, H [1 ]
机构
[1] Univ Zurich, Swiss Fed Inst Technol, Inst Pharmacol & Toxicol, CH-8057 Zurich, Switzerland
关键词
D O I
10.1016/S0165-6147(00)01646-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The enhancement of GABA-mediated synaptic transmission underlies the pharmacotherapy of various neurological and psychiatric disorders, GABA(A) receptors are pluripotent drug targets that display an extraordinary structural heterogeneity: they are assembled from a repertoire of at least 18 subunits (alpha1-6, beta1-3, gamma1-3, delta,epsilon,theta, rho1-3). However, differentiating defined GABA, receptor subtypes on the basis of function has had to await recent progress in the genetic dissection of receptor subtypes in vivo. Evidence that the various actions of allosteric modulators of GABA(A) receptors, in particular the benzodiazepines, can be attributed to specific GABA(A) receptor subtypes will be discussed, Such discoveries could open up new avenues for drug development.
引用
收藏
页码:188 / 194
页数:7
相关论文
共 45 条
  • [1] Barnard EA, 1998, PHARMACOL REV, V50, P291
  • [2] Pharmacology of recombinant γ-aminobutyric acida receptors rendered diazepam-insensitive by point-mutated α-subunits
    Benson, JA
    Löw, K
    Keist, R
    Mohler, H
    Rudolph, U
    [J]. FEBS LETTERS, 1998, 431 (03) : 400 - 404
  • [3] Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance
    Brickley, SG
    Revilla, V
    Cull-Candy, SG
    Wisden, W
    Farrant, M
    [J]. NATURE, 2001, 409 (6816) : 88 - 92
  • [4] Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues
    Crestani, F
    Lorez, M
    Baer, K
    Essrich, C
    Benke, D
    Laurent, JP
    Belzung, C
    Fritschy, JM
    Lüscher, B
    Mohler, H
    [J]. NATURE NEUROSCIENCE, 1999, 2 (09) : 833 - 839
  • [5] Mechanism of action of the hypnotic zolpidem in vivo
    Crestani, F
    Martin, JR
    Möhler, H
    Rudolph, U
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 2000, 131 (07) : 1251 - 1254
  • [6] Resolving differences in GABAA receptor mutant mouse studies
    Crestani, F
    Martini, JR
    Möhler, H
    Rudolph, U
    [J]. NATURE NEUROSCIENCE, 2000, 3 (11) : 1059 - 1059
  • [7] Dämgen K, 1999, NEUROSCI RES COMMUN, V25, P139, DOI 10.1002/(SICI)1520-6769(199911/12)25:3<139::AID-NRC3>3.0.CO
  • [8] 2-W
  • [9] DeLorey TM, 1998, J NEUROSCI, V18, P8505
  • [10] DEPOORTERE H, 1986, J PHARMACOL EXP THER, V237, P649