Ziconotide

Source: Wikipedia, the free encyclopedia.

Ziconotide
Clinical data
Pronunciation/zˈkɒntd/
zy-KON-oh-tyd
Other namesSNX–111
AHFS/Drugs.comMonograph
License data
Intrathecal – directly into cerebrospinal fluid by a catheter
ATC code
Legal status
Legal status
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
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Ziconotide, sold under the brand name Prialt, also called

intrathecal ziconotide (ITZ) because of its administration route, is an atypical analgesic agent for the amelioration of severe and chronic pain. Derived from Conus magus, a cone snail, it is the synthetic form of an ω-conotoxin peptide.[1] It is 1,000 times as powerful as morphine.[citation needed
]

In December 2004 the

.

Discovery

Ziconotide is derived from the toxin of the cone snail species Conus magus. Scientists have been intrigued by the effects of the thousands of chemicals in marine snail toxins since the initial investigations in the late 1960s by Baldomero Olivera. Olivera, now a professor of biology in the University of Utah, was inspired by accounts of the deadly effects of these toxins from his childhood in the Philippines. Ziconotide was discovered in the early 1980s by University of Utah research scientist Michael McIntosh,[2] when he was barely out of high school and working with Baldomero Olivera.[3]

Ziconotide was developed into an artificially manufactured drug by Elan Corporation. It was approved for sale under the name Prialt by the U.S. Food and Drug Administration on December 28, 2004, and by the European Commission on February 22, 2005. Azur Pharma acquired worldwide rights (except Europe) to Prialt in 2010.

Mechanism of action

Ziconotide is a hydrophilic molecule that is freely soluble in water and is practically insoluble in

glutamate, calcitonin gene-related peptide (CGRP), and substance P in the brain and spinal cord, resulting in pain relief.[5]

Therapeutic use

Due to the profound side effects or lack of efficacy when delivered through more common routes, such as orally or intravenously, ziconotide must be administered

analgesics, adjunctive therapies or IT morphine".[7] Research is ongoing to determine whether ziconotide can be formulated in a way that would allow it to be administered by less invasive means.[8][9]

However, this must be weighed against the high level of

mental disorders (e.g., psychosis) due to evidence that they are more susceptible to certain severe side effects.[12]

Adverse reactions

The most common side effects are dizziness,

seizures. Therefore, it is contraindicated in people with a history of psychosis, schizophrenia, clinical depression, and bipolar disorder. Recent incidents suggesting a link between intrathecal ziconotide treatment and increased risk of suicide have led to calls for strict and ongoing psychiatric monitoring of patients to avoid suicide occurring in vulnerable individuals.[13]
There is no known antidote.

Structure

Ziconotide is a peptide with the amino acid sequence H-Cys-Lys-Gly-Lys-Gly-Ala-Lys-Cys-Ser-Arg-Leu-Met-Tyr-Asp-Cys-Cys-Thr-Gly-Ser-Cys-Arg-Ser-Gly-Lys-Cys-NH2 (CKGKGAKCSRLMYDCCTGSCRSGKC-NH2) and contains 3 disulfide bonds (Cys1-Cys16, Cys8-Cys20, and Cys15-Cys25).

Patents

The drug was patented by Neurex Corp., a U.S. company purchased in 1998 by Élan Corporation, plc of Ireland. U.S. patents assigned to Elan include 5,859,186, 5,795,864 5,770,690, 5,587,454, and 5,587,454.

References

  1. ^ "Prialt solution for infusion - Summary of Product Characteristics (SmPC) - (eMC)". Electronic Medicines Compendium. January 2017. Retrieved April 21, 2018.
  2. PMID 7149738
    .
  3. ^ "NIGMS – Findings, September 2002: Secrets of the Killer Snails". Retrieved December 21, 2007.
  4. PMID 15578997
    .
  5. ^ .
  6. ^ "Medscape". Retrieved December 21, 2007.
  7. ^ "U.S. Pharmacist". Retrieved December 21, 2007.
  8. PMID 26234920
    .
  9. ^ Palca J (August 3, 2015). "Snail Venom Yields Potent Painkiller, But Delivering The Drug Is Tricky". NPR. Retrieved August 5, 2015.
  10. PMID 16845440
    .
  11. .
  12. ^ prialt.com Archived March 15, 2006, at the Wayback Machine
  13. S2CID 33370759
    .

External links

  • "Ziconotide". Drug Information Portal. U.S. National Library of Medicine.
  • Clinical trial number NCT00076544 for "Ziconotide Effectiveness and Safety Trial in Patients with Chronic Severe Pain" at ClinicalTrials.gov