Ziconotide

also known as: Prialt, SNX-111, Omega-Conotoxin MVIIA

A cone snail venom peptide turned FDA-approved painkiller — the first non-opioid intrathecal analgesic for severe chronic pain.

A synthetic 25-amino-acid peptide derived from the venom of Conus magus that selectively blocks N-type voltage-gated calcium channels (Cav2.2) in spinal pain pathways, FDA-approved as an intrathecal infusion for severe chronic pain refractory to opioids.

Mechanism of action

Selectively blocks N-type voltage-gated calcium channels (Cav2.2) on presynaptic nociceptive afferents in the spinal cord dorsal horn, inhibiting release of glutamate, CGRP, and substance P. Does not bind opioid receptors. No tolerance development in long-term studies.

Primary uses

Severe chronic pain refractory to other analgesics (FDA-approved)
Cancer-related intractable pain
Non-opioid analgesic alternative (no respiratory depression, no tolerance)

Typical dosing

2.4-19.2 mcg/day continuous intrathecal infusion (intrathecal (via implanted pump))

Initial dose <=2.4 mcg/day. Maximum 19.2 mcg/day. Cannot be given IV/IM/SC/oral. FDA black box warning for psychiatric side effects.

Regulatory status

FDA-approved December 2004 as Prialt (intrathecal infusion via implanted pump) for severe chronic pain in patients intolerant or refractory to other analgesics including intrathecal morphine.

References

[pubmed] Staats PS, et al. "Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS." JAMA. 2004;291(1):63-70.
[pubmed] Olivera BM, et al. "Peptide neurotoxins from fish-hunting cone snails." Science. 1985;230(4732):1338-1343.

Related peptides

Beta-Endorphin

The body's most potent endogenous painkiller — the 31-amino-acid opioid peptide behind the 'runner's high' and natural pain modulation.

Enkephalin

The body's short-acting local painkillers — five-amino-acid opioid peptides that modulate pain, mood, and gut motility at the synaptic level.

Substance P

The pain and nausea neuropeptide — an 11-amino-acid tachykinin that transmits pain signals and triggers vomiting, targeted by aprepitant (Emend) and the entire NK1 antagonist drug class.

CGRP

The migraine molecule — the most powerful vasodilator in the body and the key mediator of migraine pain, targeted by the blockbuster anti-CGRP drug class (erenumab, galcanezumab, fremanezumab, rimegepant).

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.