Pharmazentrum Frankfurt/ZAFES, Institut für Klinische Pharmakologie, Goethe-Universität, Frankfurt am Main, Germany.
Lancet. 2010 May 1;375(9725):1569-77. doi: 10.1016/S0140-6736(10)60354-6. Epub 2010 Apr 21.
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.
目前可用的镇痛药物难以实现严重慢性疼痛的药物治疗，这仍然是一个巨大的未满足的治疗需求。合成肽类药物唑尼沙胺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对其他治疗方式无效的严重慢性疼痛患者。唑尼沙胺是新型药物类别的选择性 N 型电压门控钙通道阻滞剂的首个成员。唑尼沙胺在脊髓中对 N 型钙通道的阻滞抑制了初级传入神经元中枢末端与疼痛相关的神经递质的释放。通过这种机制，唑尼沙胺可以有效地减轻疼痛。然而，由于中枢神经系统副作用较大，唑尼沙胺的治疗窗较窄，因此只有一小部分严重慢性疼痛患者适合使用唑尼沙胺治疗。我们提供了鞘内唑尼沙胺治疗的益处和局限性的概述，并回顾了这一新药物类别的潜在未来发展。
