N-型钙通道及其阻断剂研究进展

N-型电压依赖性钙通道主要分布于疼痛传递与调控通路的神经元突触末梢，参与疼痛介质(如谷氨酸和P物质)的释放和调节，在疼痛传递和调控过程中具有重要作用。因此，阻断N 型钙通道可以产生镇痛作用，特别是慢性疼痛和神经病理性疼痛。FDA已批准肽类阻断剂齐考诺肽鞘内给药，治疗全身性疼痛以及吗啡耐受或无效患者的严重慢性疼痛，证实N型钙通道是一个非常有意义的镇痛药物研究新靶标。近年来，口服有活性的小分子化合物研究越来越受到人们的重视，各种文献和专利报道的新结构类型层出不穷。本文就相关研究进行了综述。

Research progress in N-type calcium channel and its blockers

N-type calcium channels are mainly present at the presynaptic terminals of nociceptive neurons which are critical for pain transduction and modulation. These channels are involved in the release and regulation of the nociceptive neurotransmitters such as glutamate and substance P. Thus, the selective blockage of the N type channels can produce powerful analgesic effect, especially for chronic and neuropathic pain. FDA has approved the use of the peptide ziconotide for treatment of all kinds of pain, including morphine refractory or morphine unresponsive malignant pain via intrathecal administration, which suggests that N-type calcium channel is a significant target for developing new type analgesics. Researchers have made great efforts in discovery of small molecules with oral activity and several new structures have been reported in literature and patents in recent years. The related research progress is reviewed in the present article.