Ziconotide peptide, the product name is Prialt, which is an artificially synthesized ω - conotoxin MVIIA and belongs to intrathecal injection analgesics. It exerts a potent analgesic effect by specifically blocking the N-type voltage-gated calcium channel (CaV2.2) in the spinal dorsal horn, inhibiting the release of pain neurotransmitters. Approved by the US FDA and the European Union in 2004, it is suitable for severe chronic pain patients who have failed other analgesic treatments (such as systemic analgesics or intrathecal morphine), especially for cancer pain and refractory neuropathic pain.
Information source: Baidu Baike "Qikao Nuo Peptide"; The WeChat public platform (Tencent) has released the article "Chikunotide and Intrathecal Injection, Safe and Effective Difficult to Treat Pain Treatment Drugs, Non Drug Resistant and Addictive"
Products form
Ziconotide Polyacetate COA
Basic information and target of action
Ziconotide peptide is a peptide compound containing 25 amino acids, with three disulfide bonds in the molecule that form a stable "cysteine Knot" topology. This structure significantly enhances the chemical stability and conformational rigidity of peptide molecules, making them less susceptible to protease degradation in vivo, while also providing a specific spatial conformation for their binding to target receptors. Its isoelectric point (pI) is approximately 8.5-9.0, and due to the presence of multiple basic amino acid residues (such as lysine and arginine) in the molecule, it exhibits weak alkalinity overall. It has a certain solubility in water, usually soluble in neutral or weakly acidic buffer solutions (such as phosphate buffer solution, acetic acid buffer solution), but has lower solubility in organic solvents (such as methanol, ethanol), and is almost insoluble in non-polar solvents (such as ether, chloroform).
Information source: ChemicalBook related article "Ziconotide; 107452-89-1", published on October 14, 2025.
Voltage gated calcium channels (VGCCs) are an important class of proteins that control calcium ion transport in cells. Based on their sequence differences, they can be divided into multiple subfamilies, among which CaV2.2 (N-type voltage-gated calcium channels in neural tissue) plays an important role in neurotransmitter release. When the cell membrane potential changes, CaV2.2 is immediately activated, opening the channel gate and allowing messenger calcium ions (Ca ² ⁺) to smoothly enter the membrane from outside, thereby promoting the release of neurotransmitters and triggering a series of downstream signaling pathways.
During the transmission of pain signals, nociceptive stimuli activate peripheral nociceptors, and the signals are transmitted to the spinal cord through primary afferent nerve fibers (mainly mildly myelinated A δ - and C-fibers). In this process, the activation of N-type channels mediates the release of neurotransmitters such as substance P (SP), calcitonin gene-related peptide (CGRP), and glutamate, which affect downstream neural activation and pain perception. SP and CGRP can also induce inflammation and exacerbate chronic inflammatory pain.
Information source:
The relevant article of the Chinese Academy of Sciences, "This" Horse "Led the Way for Painkiller Research and Development", was released on July 8, 2021.
The article related to Zhihu Column, "Structure of human Cav2.2 channel blocked by the painkiller ziconotide", was published on July 7, 2021 (this article introduces the research results of Yan Ning's team at Princeton University published in Nature, revealing the molecular basis of ziconotide blocking Cav2.2 specific pores).
The mechanism of blocking N-type calcium channels
Can specifically bind to the α - κ B subunit of N-type calcium channels on the neuronal cell membrane. Structurally, Chikanootide is fully coordinated by helices P1 and P2, which support selective filters and the extracellular loop (ECL) in α - repeat II, III, and IV. In order to adapt to its binding, the ECL of repeat III and α ₂ δ -1 must be consistently tilted upwards. Research has shown that the insertion of the Met12 residue of ziconotide peptide into the hydrophobic pocket formed by Ile300, Phe302, and Leu305 in CaV2.2 increases its binding affinity to the target, but may also be associated with some toxic adverse reactions.
Information source: Zhihu Column related article "Structure of Human Cav2.2 Channel Blocked by the Painkiller Ziconotide", published on July 7, 2021.
When the substance binds to N-type calcium channels, it directly blocks the ion channel pores, preventing the transmembrane transport of calcium ions (Ca ² ⁺) into neurons. Under normal physiological conditions, calcium ion influx is a key link in neurotransmitter release. For example, at the primary afferent nerve endings, the influx of calcium ions mediated by N-type calcium channels promotes the release of neurotransmitters such as substance P, CGRP, and glutamate. And by blocking this process, the release of these pain related neurotransmitters is reduced. Animal experiments have shown that after administration, the release of excitatory neurotransmitters from primary afferent nerve endings is significantly reduced, thereby exerting analgesic effects.
Information source:
The related article on Sohu website "Ziconotide; 107452-89-1; CKGKGAKCSRLMYDCCTGSCRSGKC_ Responsive_Dosy_Neuro" was published on March 16, 2025.
MCE (Shanghai Haoyuan Biopharmaceutical Technology Co., Ltd.) related article "Aconotide acetate", published on November 3, 2016 (the article mentions that Aconotide acetate can reduce calcium current caused by the expression of α 1B subunit in HEK cells, tsa-201 cells, and Xenopus laevis oocytes, indicating that it can reduce calcium ion influx).
The impact of the mechanism of action on the transmission of pain signals
(1) Inhibit the release of neurotransmitters from primary afferent nerve endings
As mentioned earlier, after the activation of peripheral nociceptors by nociceptive stimuli, signals are transmitted to the spinal cord through primary afferent nerve fibers. During this process, the activation of N-type calcium channels at the primary nerve endings leads to the influx of calcium ions, which in turn triggers the release of neurotransmitters such as substance P, CGRP, and glutamate. These neurotransmitters transmit pain signals to neurons in the dorsal horn of the spinal cord, which are further transmitted to the brain to generate pain perception.
Ziconotide peptide inhibits the influx of calcium ions by blocking N-type calcium channels, thereby reducing the release of these neurotransmitters. For example, in the experimental autoimmune encephalomyelitis (EAE) mouse model, after administration, the levels of IL-1 β and IL-23 in the central nervous system of the mice decreased, and the amount of IL-17 produced in the spleen also decreased. This indicates that Ziconotide affects the release of neurotransmitters and the production of related inflammatory factors, thereby alleviating pain symptoms.
Information source: MCE (Shanghai Haoyuan Biopharmaceutical Technology Co., Ltd.) related article "Zinc acetate", published on November 3, 2016.
(2) Block the transmission of pain signals to the brain
The spinal cord is an important relay station for the transmission of pain signals. After the primary afferent nerves transmit the pain signals to the dorsal horn of the spinal cord, they are processed by a complex neural network and then transmitted to the brain by spinal projection neurons. Plays a role at the spinal cord level by inhibiting the release of neurotransmitters from primary afferent nerve endings, reducing the activation of spinal dorsal horn neurons and thereby blocking further transmission of pain signals to the brain.
Clinical studies have shown that intrathecal injection of Ziconotide can effectively alleviate pain in patients with severe chronic pain who are unresponsive or intolerant to other treatments such as intrathecal morphine and systemic analgesics.
For example, in some clinical studies using slow dose titration regimens, the initial dose does not exceed 2.4 μ g/24 hours (0.1 μ g/hour), and the dose is increased 2-3 times a week based on patient response, with each increment not exceeding 2.4 μ g/24 hours (0.1 μ g/hour). By the 21st day, the maximum recommended dose is 19.2 μ g/24 hours (0.8 μ g/hour), and many patients' pain has been significantly relieved, thanks to its effective blockade of pain signal transmission.
Information source: Relevant article on Sohu website titled "Ziconotide; 107452-89-1; CKGKGAKCSRLMYDCCTGSCRSGKC_ Responsiveness, Dose, and Neurology", published on March 16, 2025.
Ziconotide peptide, as a specific N-type voltage-gated calcium channel blocker, blocks the influx of calcium ions by binding to the α - κ B subunit of N-type calcium channels, inhibits the release of neurotransmitters from primary afferent nerve endings, and thus blocks the transmission of pain signals to the brain, exerting a potent analgesic effect. Its unique mechanism of action gives it advantages such as non addiction and intolerance, providing a safe and effective treatment option for patients with severe chronic pain, especially neuropathic pain and cancer pain.
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