Chizh B A
Department of Pharmacology, Grünenthal GmbH R&D, Aachen, Germany.
Amino Acids. 2002;23(1-3):169-76. doi: 10.1007/s00726-001-0124-4.
Glutamatergic mechanisms are implicated in acute and chronic pain, and there is a great diversity of glutamate receptors that can be used as targets for novel analgesics. Some approaches, e.g. NMDA receptor antagonism, have been validated clinically, however, the central side-effects have remained the main problem with most compounds. Recently, some novel approaches have been explored as new compounds targeting some modulatory sites at the NMDA receptor (glycine(B) and NR2B-subtype selective antagonists), as well as kainate and metabotropic glutamate receptors, have been discovered. Many of these compounds have demonstrated efficacy in animal models of chronic pain, and some of them appear to have a reduced side-effect liability compared to clinically tested NMDA antagonists. These recent advances are reviewed in the present work.
谷氨酸能机制与急慢性疼痛有关，并且存在多种多样的谷氨酸受体，它们可作为新型镇痛药的靶点。一些方法，如NMDA受体拮抗作用，已在临床上得到验证，然而，中枢副作用一直是大多数化合物的主要问题。最近，已经探索了一些新方法，因为发现了一些靶向NMDA受体某些调节位点（甘氨酸（B）和NR2B亚型选择性拮抗剂）以及海人藻酸和代谢型谷氨酸受体的新化合物。这些化合物中的许多已在慢性疼痛动物模型中显示出疗效，并且其中一些与经过临床测试的NMDA拮抗剂相比，似乎副作用更小。本研究对这些最新进展进行了综述。
