Conotoxin MVIIA
Omega-conotoxin from Conus magus that blocks N-type calcium channels, used as an intrathecal analgesic for severe chronic pain.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C102H172N36O32S7 |
| Molecular Weight | 2639 Da |
| CAS Number | 107452-89-1 |
| Peptide Class | Omega-Conotoxin (25 amino acids) |
| Origin | Conus magus (cone snail) |
| Disulfide Bonds | 3 |
Structure
Conotoxin MVIIA (ziconotide) is a 25-amino acid peptide with three disulfide bonds forming a compact knottin scaffold. It belongs to the omega-conotoxin family, characterized by the cysteine framework VI/VII. The peptide contains multiple post-translational modifications including C-terminal amidation and hydroxyproline.
Mechanism of Action
MVIIA selectively blocks N-type voltage-gated calcium channels (Cav2.2) in the dorsal horn of the spinal cord. By inhibiting presynaptic calcium influx, it reduces release of pain-mediating neurotransmitters (substance P, CGRP, glutamate) from primary afferent nociceptors, providing potent analgesia without opioid tolerance.
Clinical Applications
- Severe chronic pain: Intrathecal ziconotide (Prialt) for cancer and non-cancer pain
- Opioid-refractory pain: Alternative to escalating opioid doses
- Neuropathic pain: Spinal cord injury-related pain
- Cancer pain: Adjunct to intrathecal morphine
Pharmacokinetics
- Half-life: 4.6 hours (intrathecal)
- CSF levels: 100-1000x higher than plasma
- Metabolism: Proteolytic cleavage
- Elimination: Renal
- Route: Intrathecal only (continuous infusion via pump)
Safety and Side Effects
Dizziness (50%), nausea (30%), confusion (25%), nystagmus, ataxia, memory impairment, hallucinations, and psychiatric symptoms. Slow dose titration required to minimize CNS effects.
References
- Staats, P.S., et al. (2004). Intrathecal ziconotide for chronic pain. New England Journal of Medicine, 350, 1557-1564.
- Miljanich, G.P. (2004). Ziconotide: neuronal calcium channel blocker. Current Medicinal Chemistry, 11, 3029-3040.
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