From the Guidelines
Ziconotide works on presynaptic terminals in the dorsal horn of the spinal cord. This synthetic peptide, derived from the venom of the cone snail Conus magus, selectively blocks N-type calcium channels located on presynaptic nerve terminals 1. By blocking these channels, ziconotide prevents calcium influx into the presynaptic terminals, which inhibits the release of pain-transmitting neurotransmitters such as glutamate, substance P, and calcitonin gene-related peptide. This mechanism effectively interrupts pain signal transmission from primary afferent neurons to second-order neurons in the dorsal horn. The use of ziconotide is supported by recent guidelines, including those from the European Society for Medical Oncology (ESMO) 1, which recommend its use in patients with severe chronic pain that is refractory to other treatments. Ziconotide is administered exclusively via intrathecal infusion because it cannot cross the blood-brain barrier and would be degraded if given orally. The drug is particularly valuable for managing severe chronic pain, though its use requires careful monitoring due to potential neuropsychiatric side effects and a narrow therapeutic window. Key points to consider when using ziconotide include:
- Its administration via intrathecal infusion, which requires careful monitoring and management
- Its potential for neuropsychiatric side effects, which must be carefully assessed and managed
- Its narrow therapeutic window, which requires careful dose adjustment and monitoring
- Its use in patients with severe chronic pain that is refractory to other treatments, as recommended by recent guidelines 1.
From the FDA Drug Label
Ziconotide binds to N-type calcium channels located on the primary nociceptive (A-δ and C) afferent nerves in the superficial layers (Rexed laminae I and II) of the dorsal horn in the spinal cord Although the mechanism of action of ziconotide has not been established in humans, results in animals suggest that its binding blocks N-type calcium channels, which leads to a blockade of excitatory neurotransmitter release from the primary afferent nerve terminals and antinociception.
Ziconotide works on presynaptic terminals in the dorsal horn of the spinal cord.
- The mechanism of action involves binding to N-type calcium channels, which blocks excitatory neurotransmitter release from primary afferent nerve terminals.
- This leads to antinociception, or pain relief, in patients with chronic pain 2.
From the Research
Ziconotide Mechanism of Action
- Ziconotide is a N-type Ca2+ channel antagonist used in intrathecal infusions that works on presynaptic terminals in the dorsal horn of the spinal cord 3, 4.
- The drug blocks the entry of calcium into neuronal N-type voltage-sensitive calcium channels, preventing the conduction of nerve signals 3.
- N-type calcium channels are present in the superficial laminae of the dorsal horn of the spinal cord, where ziconotide produces potent analgesia by interruption of Ca-dependent primary afferent transmission of pain signals 5, 4.
- The mechanism of action of ziconotide involves potent and selective block of N-type calcium channels, which control neurotransmission at many synapses, resulting in the interruption of pain signaling at the level of the spinal cord 6.