Laube Bodo, Maksay Gábor, Schemm Rudolf, Betz Heinrich
Dept. of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, 60528, Frankfurt, Germany.
Trends Pharmacol Sci. 2002 Nov;23(11):519-27. doi: 10.1016/s0165-6147(02)02138-7.
Transmitter-gated ion channels mediate rapid synaptic transmission in the CNS and constitute important targets for many neuroactive drugs. Inhibitory glycine receptors (GlyRs) are members of the nicotinic acetylcholine receptor superfamily and inhibit neuronal firing by opening Cl(-) channels following agonist binding. In this article, we discuss recent developments in GlyR pharmacology, delineate the receptor domains that are involved in binding of agonists and allosteric modulators, and present a molecular model of the extracellular architecture of the receptor. The recent discovery of compounds that act preferentially on specific GlyR isoforms and the differential expression of these isoforms in distinct regions of the developing and adult CNS show considerable promise towards the development of drugs that act in defined glycine-mediated pathways. In particular, compounds that can potentiate GlyR function should provide leads for novel muscle relaxants in addition to sedative and analgesic agents.
递质门控离子通道介导中枢神经系统中的快速突触传递，并且是许多神经活性药物的重要作用靶点。抑制性甘氨酸受体（GlyRs）是烟碱型乙酰胆碱受体超家族的成员，在激动剂结合后通过打开Cl(-)通道来抑制神经元放电。在本文中，我们讨论了甘氨酸受体药理学的最新进展，描绘了参与激动剂和变构调节剂结合的受体结构域，并提出了该受体细胞外结构的分子模型。最近发现的优先作用于特定甘氨酸受体亚型的化合物，以及这些亚型在发育中和成年中枢神经系统不同区域的差异表达，为开发作用于特定甘氨酸介导途径的药物带来了很大希望。特别是，能够增强甘氨酸受体功能的化合物除了可作为镇静剂和镇痛剂外，还应为新型肌肉松弛剂提供线索。
