Gao Zhan-Guo, Jacobson Kenneth A
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Drug Discov Today. 2006 Mar;11(5-6):191-202. doi: 10.1016/S1359-6446(05)03689-5.
Allosteric modulation of membrane receptors has been intensively studied in the past three decades and is now considered to be an important indirect mechanism for the control of receptor function. The allosteric site on the GABA(A) receptor is the target for the most widely prescribed sleep medicines, the benzodiazepines. Cinacalcet, an allosteric enhancer of the calcium-sensing receptor, is used to treat secondary hyperparathyroidism. Allosteric ligands might be especially valuable to control receptors for which the design of selective orthosteric agonists or antagonists has been elusive, such as muscarinic acetylcholine receptors.
在过去三十年中，人们对膜受体的变构调节进行了深入研究，目前认为这是控制受体功能的一种重要间接机制。GABA(A)受体上的变构位点是应用最为广泛的助眠药物——苯二氮䓬类药物的作用靶点。西那卡塞作为钙敏感受体的变构增强剂，用于治疗继发性甲状旁腺功能亢进。对于那些难以设计出选择性正构激动剂或拮抗剂的受体，如毒蕈碱型乙酰胆碱受体，变构配体可能具有特殊价值。
