Schroeder C I, Doering C J, Zamponi G W, Lewis R J
Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
Med Chem. 2006 Sep;2(5):535-43. doi: 10.2174/157340606778250216.
Highly selective Ca(v)2.2 voltage-gated calcium channel (VGCC) inhibitors have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Cone snail venoms provided the first drug in class with FDA approval granted in 2005 to Prialt (omega-conotoxin MVIIA, Elan) for the treatment of neuropathic pain. Since this pioneering work, major efforts underway to develop alternative small molecule inhibitors of Ca(v)2.2 calcium channel have met with varied success. This review focuses on the properties of the Ca(v)2.2 calcium channel in different pain states, the action of omega-conotoxins GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved Ca(v)2.2 calcium channel therapeutics, and finally the development of small molecules for the treatment of chronic pain.
高选择性Ca(v)2.2电压门控钙通道（VGCC）抑制剂已成为治疗慢性疼痛和神经性疼痛的一类新型疗法。锥蜗牛毒液提供了该类别的第一种药物，2005年美国食品药品监督管理局（FDA）批准Prialt（ω-芋螺毒素MVIIA，爱尔兰伊兰公司）用于治疗神经性疼痛。自这项开创性工作以来，为开发Ca(v)2.2钙通道的替代小分子抑制剂所做的主要努力取得了不同程度的成功。本综述重点关注Ca(v)2.2钙通道在不同疼痛状态下的特性、ω-芋螺毒素GVIA、MVIIA和CVID的作用，描述它们的构效关系以及作为设计改进型Ca(v)2.2钙通道疗法先导物的潜力，最后介绍用于治疗慢性疼痛的小分子的开发情况。
