Ziconotide
Ziconotide is a synthetic omega-conotoxin MVIIA peptide that blocks N-type calcium channels, approved for severe chronic pain via intrathecal delivery.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C102H172N36O32S7 |
| Molecular Weight | 2639.14 g/mol |
| CAS Number | 107452-89-1 |
| IUPAC Name | Synthetic omega-conopeptide MVIIA |
| Peptide Class | N-type Calcium Channel Blocker |
| Sequence Homology | Synthetic version of Conus magus toxin |
Structure
Ziconotide is a synthetic 25-amino acid peptide identical to omega-conotoxin MVIIA from the venom of the marine cone snail Conus magus. It contains three intramolecular disulfide bonds forming a compact, rigid structure. The peptide belongs to the omega-conotoxin family characterized by a cysteine knot motif.
Mechanism of Action
Ziconotide selectively blocks N-type voltage-gated calcium channels (Cav2.2) on primary afferent neurons in the dorsal horn of the spinal cord. By inhibiting calcium influx at presynaptic terminals, it prevents the release of pro-nociceptive neurotransmitters including substance P, glutamate, and CGRP. Unlike opioid analgesics, ziconotide does not produce tolerance or physical dependence.
Clinical Applications
Ziconotide (Prialt) is approved for:
- Severe chronic pain: Management of severe chronic pain in patients who require intrathecal therapy
- Cancer pain: Refractory cancer pain unresponsive to other treatments
- Non-malignant chronic pain: Failed back surgery syndrome, complex regional pain syndrome
Administered exclusively via continuous intrathecal infusion using an implanted pump, as systemic administration causes intolerable side effects.
Pharmacokinetics
- Half-life: 2.9-6.5 hours (intrathecal)
- Tmax: Immediate (intrathecal)
- Bioavailability: 100% intrathecally; negligible systemic bioavailability
- Metabolism: Proteolytic degradation in CSF and systemic circulation
- Distribution: Confined to CSF after intrathecal administration
Safety and Side Effects
Adverse effects include dizziness (30%), nausea (27%), confusion (11%), abnormal gait (9%), memory impairment (6%), and psychiatric symptoms (hallucinations, paranoia). Contraindicated in patients with pre-existing psychosis or those receiving intrathecal infusions via non-proprietary pumps. Must be titrated slowly to minimize CNS adverse effects. Not an opioid; no abuse potential.
References
- Staats, P.S., et al. (2004). Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS. JAMA, 291, 63-70.
- Miljanich, G.P. (2004). Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Current Medicinal Chemistry, 11, 3029-3040.
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