Ziconotide for treatment of severe chronic pain
Ziconotide for treatment of severe chronic pain
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DOI：
10.1016/s0140-6736(10)60354-6
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发表时间：
2010-05-01
期刊：
影响因子：
168.9
通讯作者：
Geisslinger, Gerd
中科院分区：
文献类型：
--
作者：
Schmidtko, Achim;Loetsch, Joern;Geisslinger, Gerd
严重慢性疼痛的药理学管理很难用目前可用的镇痛药物实现，并且仍然是一个很大的未满足的治疗需求。合成肽齐考诺肽已被美国食品药品监督管理局和欧洲药品管理局批准用于鞘内治疗其他治疗方式难以治疗的严重慢性疼痛患者。齐考诺肽是选择性N型电压敏感性钙通道阻滞剂新药类别中的第一个成员。齐考诺肽诱导的脊髓N型钙通道阻滞抑制初级传入神经元中枢终末疼痛相关神经递质的释放。通过这种机制，齐考诺肽可以有效地减轻疼痛。然而，齐考诺肽具有狭窄的治疗窗口，因为大量的CNS副作用，因此用齐考诺肽治疗仅适用于患有严重慢性疼痛的一小部分患者。我们提供了鞘内齐考诺肽治疗的益处和局限性的概述，并回顾了这类新药未来的潜在发展。
Pharmacological management of severe chronic pain is difficult to achieve with currently available analgesic drugs, and remains a large unmet therapeutic need. The synthetic peptide ziconotide has been approved by the US Food and Drug Administration and the European Medicines Agency for intrathecal treatment of patients with severe chronic pain that is refractory to other treatment modalities. Ziconotide is the first member in the new drug class of selective N-type voltage-sensitive calcium-channel blockers. The ziconotide-induced blockade of N-type calcium channels in the spinal cord inhibits release of pain-relevant neurotransmitters from central terminals of primary afferent neurons. By this mechanism, ziconotide can effectively reduce pain. However, ziconotide has a narrow therapeutic window because of substantial CNS side-effects, and thus treatment with ziconotide is appropriate for only a small subset of patients with severe chronic pain. We provide an overview of the benefits and limitations of intrathecal ziconotide treatment and review potential future developments in this new drug class.