齐考诺肽 (Prialt)

概览

Ziconotide is an N-type calcium channel antagonist used to manage patients with severe chronic pain who cannot tolerate, or who have not responded adequately to other treatments such as intrathecal morphine and systemic analgesics.

作用机制

Nociceptive pain signalling is a complex processing pathway involving peripheral nociceptors, primary afferent nerve fibres, and downstream CNS neurons located in the spinal cord. Voltage-gated calcium channels (VGCCs) are important regulatory components of neural signalling and include the N-type (Cav2.2) heteromultimeric high-voltage type calcium channels. Chronic pain conditions, including inflammatory and neuropathic pain, often involve the aberrant upregulation of VGCC activity through various cellular mechanisms, which can lead to allodynia and hyperalgesia. Specifically, N-type channel activation in lightly myelinated Aδ- and C-fibres is known to mediate the release of neurotransmitters substance P (SP), calcitonin gene-related peptide (CGRP), and glutamate, which influence downstream neural activation and pain perception. In addition, SP and CGRP induce inflammation, potentially exacerbating pre-existing inflammatory chronic pain. Ziconotide belongs to the ω-conotoxin class of neurotoxic peptides derived from the cone snail Conus magus which are capable of inhibiting N-type VGCCs. Although the exact mechanism is yet to be elucidated, it is thought that ω-conotoxins function through direct occlusion of the ion pore to prevent calcium translocation across the membrane. Additional studies involving expression of chimeric subunits and molecular modelling suggest that insertion of the ziconotide Met residue into a hydrophobic pocket formed by Ile, Phe, and Leu of Cav2.2 increases binding and may be associated with toxic adverse effects.

适应症

用于需要鞘内治疗且对其他镇痛治疗（如应用全身性镇痛药或鞘内注射吗啡等）不耐受或疗效差的严重慢性疼痛患者。

• Severe, Chronic Pain