Ziconotide

from Wikipedia, the free encyclopedia
Omega conotoxin MVIIA ( Conus magus )
Omega conotoxin MVIIA (Conus magus)
Protein backbone, disulfide bridges yellow, according to PDB  1DW5
Mass / length primary structure 2639 daltons , 25 amino acids
Secondary to quaternary structure cyclic, 3 disulfide bridges
Identifier
Gene name (s) MVIIA precursor (Conoserver)
External IDs
Drug information
ATC code N02 BG08
Drug class Painkiller
Occurrence
Parent taxon Cone snails

Ziconotide (trade name Prialt ) is a cyclic peptide made up of 25 amino acids. This substance, originally isolated from the venom of the cone snail Conus magus as ω- conotoxin MVIIA , is synthetically produced and used as a medicinal substance for the treatment of severe chronic pain.

Mechanism of action

Ziconotide is a N-type calcium channel blocker ( neuronal calcium channel blocker , NCCB). It works by blocking calcium from flowing into the primary nociceptive afferent nerves that terminate in the superficial layers of the posterior horn of the spinal cord . As a result, the release of neurotransmitters is inhibited and the conduction of pain is prevented.

Ziconotide is also neuroprotective .

Ziconotide has no effect on opioid receptors and thus belongs to the non-opioid analgesics .

Clinical studies on ω-conotoxin MVIIA have shown that the substance is about a thousand times more effective than morphine, but that there is no development of tolerance.

Development history

Ziconotide has been designated as an orphan medicinal product since 2001 and was approved for the European market in 2005 as Prialt under “exceptional circumstances”. It is being discussed as a possible replacement for morphine and was considered to be one when it was discovered. In 2010, however, an increase in the risk of suicide was discussed on the basis of several individual cases .

application

Ziconotide is used medicinally as acetate and infused intrathecally into the cerebrospinal fluid via a pain pump .

Ziconotide can be combined with opioids, local anesthetics and centrally acting relaxants.

Side effects

In clinical studies, 89% of patients reported side effects. Tolerance is dose-dependent. To limit the occurrence of serious adverse drug reactions, a maximum dose of 21.6 μg / day is recommended. However, clinical studies have shown that patients who can tolerate this dose for a period of 3 to 4 weeks generally can tolerate higher doses up to 48 μg / day.

Very common side effects (occurred in more than 10% of people treated):

  • Confusion (25%)
  • Blurred vision (14%)
  • Nausea (30%) and vomiting (11%)
  • Gait disorders
  • Weakness (13%)

In addition to the side effects already mentioned, other psychiatric and neurological side effects often occur (1–10%).

Overdoses lead to stupor , myoclonus and drop in blood pressure. The intrathecal administration due to the risk for inflammation of the brain and spinal cord ( meningitis ).

Trade names

Monopreparations

Prialt (D, A)

Web links

Individual evidence

  1. ↑ Swiss Institute of Bioinformatics (SIB): PROSITE documentation PDOC60004. Omega conotoxin. Retrieved August 10, 2011 .
  2. ↑ a b c d e f Product information (information for healthcare professionals, instructions for use) on Prialt (ziconotide) (PDF; 373 kB) from the European Medicines Agency ( accessed on 19 September 2012 )
  3. ↑ a b Jain KK: An evaluation of intrathecal ziconotide for the treatment of chronic pain . In: Expert Opin Investig Drugs . 9, No. 10, October 2000, pp. 2403-2410. doi : 10.1517 / 13543784.9.10.2403 . PMID 11060815 .
  4. ↑ Ziconotide (intraspinal use) in the Community register of the European Commission.
  5. ↑ Prialt on the European Medicines Agency website .
  6. ↑ McIntosh JM, Corpuz GO, Layer RT, et al. : Isolation and characterization of a novel conus peptide with apparent antinociceptive activity . In: J Biol Chem . 275, No. 42, October 2000, pp. 32391-7. doi : 10.1074 / jbc.M003619200 . PMID 10900201 .
  7. ↑ University of Bochum November 23, 2010: Under suspicion: painkiller ziconotide could increase the tendency to suicide - experts advise precise diagnosis and strict monitoring RUB doctors warn in "PAIN" , doi : 10.1016 / j.pain.2010.10.007 .
  8. ↑ Universum Internal Medicine, April 13, 2012 , Prim. Univ.-Prof. Dr. Wilfried Ilias, Ziconotid: New insights into application
  9. ↑ swissmedic: Prialt ( Memento of the original from March 4, 2016 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.swissmedic.ch
  10. ↑ Red List Online, as of 2012.
  11. ↑ AGES PharmMed, as of February 2016.