Shipe William D, Wolkenberg Scott E, Williams David L, Lindsley Craig W
Merck Research Laboratories, Department of Medicinal Chemistry, Technology Enabled Synthesis Group, Imaging Research, PO Box 4, WP14-1, Sumneytown Pike, West Point, PA 19486, USA.
Curr Opin Drug Discov Devel. 2005 Jul;8(4):449-57.
Positive allosteric modulators of metabotropic glutamate receptors (mGluRs) are the subject of intensive research due to their emerging therapeutic potential for a range of psychiatric and neurological disorders such as pain, anxiety, cognition, Parkinson's disease and schizophrenia. Positive allosteric modulators, which are small molecules capable of enhancing agonist-mediated receptor activity while possessing no intrinsic agonist activity, have recently been described for group I (mGluR1 and mGluR5), group II (mGluR2) and group III (mGluR4) mGluRs. Relative to classical mGluR agonists, these molecules offer improved selectivity versus other mGluRs and chemical tractability, and may reduce the liability of receptor desensitization.
代谢型谷氨酸受体（mGluRs）的正变构调节剂因其在一系列精神和神经疾病（如疼痛、焦虑、认知、帕金森病和精神分裂症）中展现出的潜在治疗价值而成为深入研究的对象。正变构调节剂是一类小分子，它们能够增强激动剂介导的受体活性，但本身不具有内在激动剂活性。最近，针对I组（mGluR1和mGluR5）、II组（mGluR2）和III组（mGluR4）mGluRs的正变构调节剂已被报道。相对于经典的mGluR激动剂，这些分子对其他mGluRs具有更高的选择性和化学可加工性，并且可能降低受体脱敏的可能性。
