Ziconotide

Chemical Identity

Property	Value
Chemical Formula	C102H172N36O32S7
Molecular Weight	2639 Da
CAS Number	107452-89-1
Peptide Class	Synthetic Omega-Conotoxin (25 aa)
Route	Intrathecal continuous infusion

Structure

Ziconotide (Prialt) is a synthetic version of omega-conotoxin MVIIA from the cone snail Conus magus. The 25-amino acid peptide contains three disulfide bonds forming a compact structure. It was the first conotoxin approved for clinical use and represents the development of marine venom peptides as therapeutics.

Mechanism of Action

Ziconotide blocks N-type voltage-gated calcium channels (Cav2.2) in the superficial dorsal horn of the spinal cord. By inhibiting presynaptic calcium influx at nociceptive synapses, it reduces release of substance P, CGRP, and glutamate from primary afferent neurons. This provides potent analgesia without opioid tolerance or respiratory depression.

Clinical Applications

• Severe chronic pain: Cancer and non-cancer pain refractory to other treatments
• Neuropathic pain: Spinal cord injury, complex regional pain syndrome
• Opioid-intolerant patients: Alternative when opioids fail or cause unacceptable side effects
• Failed back surgery syndrome: Chronic post-surgical pain

Pharmacokinetics

• Half-life: 4.6 hours (intrathecal)
• CSF:plasma ratio: 100:1 to 1000:1
• Metabolism: Proteolytic degradation
• Elimination: Renal
• Route: Intrathecal via implanted pump
• Dosing: Slow titration from 0.1 to 2.4 mcg/hour

Safety and Side Effects

Dizziness (50%), nausea (30%), confusion (25%), nystagmus, ataxia, memory impairment, psychosis, and hallucinations. Slow dose titration essential to minimize CNS effects. Contraindicated in pre-existing psychosis.

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 for pain. Current Medicinal Chemistry, 11, 3029-3040.