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Reprieve of the Killer Snails

Classification: The conotoxins are so specifically targeted to their prey receptor subypes that they are capable of distinguishing protein homologues of the same tissue between species.This specificity allows separation of a whole range of receptors by studying their interactions with the conotoxins. The continuing discovery of new conotoxin subclasses each with a different specificity provides a wealth of probes to use in the classification of the increasing diversity of discovered receptors. [Top]

Pharmacology : The small size of the conotoxins ( typically 12-30 amino acids) and the high specificity that they exhibit towards receptors provides an ideal opportunity in which to study the molecular biology of receptor interactions. The small size of the toxin peptides allows the investigation of the effect of amino acid substitutions on the specificity of the conotoxin, and therefore the role of each amino acid in the receptor recognition. [Top]

Medical Uses of Conotoxins : The specificity of the conotoxins is such that it can distinguish between tissue homologues of the same protein. In the administration of drugs, the non-therapeutic binding to non-target areas often reduces the effectiveness of the application as well as resulting in various side effects. If the specificity of the conotoxins can be harnessed, therapeutic drug binding could be greatly improved.

Clinical trials:The conotoxins themselves have been shown to be useful in the treatment of some disorders. For example, the peptide toxins of Conus magus are at present undergoing clinical trials (see update below) in the USA for use in the treatment of ischaemia in stroke patients, and another conotoxin is undergoing clinical trials as a potential analgesic for intractable pain (G. Miljanich - quoted in Olivera et al 1995).

Conotoxins from other species (eg. Conus geographus, Conus catus and Conus marmoreus and others) are being developed by AMRAD Ltd, Melbourne, Australia, and Xenome Ltd. of Queensland, Australia. Licencing agreements are being sought by Nextec, Melbourne, Australia, for another class of conotoxin effective against neuropathic pain.

The k-conotoxins targeting the Potassium channels, have a potential use in the therapy of hypertension, arrhythmia and ashma.

Conantokins, originally isolated from the venom of fishing- hunting cone snails, are 17 aminoacid linear peptides that adopt an a- helical conformation in solution and contain post translational modifications including five carboxy-glutamic acid residues and an amidated C-terminal. Conantokins act on the N-Methyl-D-Aspartate (NMDA) receptors, thus promising useful applications in epilepsy, Parkinson’s disease and stroke.

Contulakins, targeting the neurotensin receptor may be employed in the therapy of pain and disorders of the central nervous system (CNS).

(See also the web site mainained by Cognetix at http://www.cognetix.com).

CG and BGL, June-95; Updated by BGL, June 2002

Clinical trials update: Omega-conotoxin MVIIA from Conus magus, termed Prialt(TM) (also previously referred to as Ziconotide,CI 1009, and SNX-111) has been trialed in humans for treatment of intractable neuropathic pain and for prevention of stroke. The FDA has requested (November 2001) a repeat of Stage III clinical trials of Ziconotide for cancer pain. For this purpose, Ziconotide has been re-badged Prialt(TM):

  • Read updated information from the US National Library of Medicine [re-use for Pain related to HIV and Cancer],
  • and from "Ziconotide" at DocMD.com - "a New Drug Application (NDA) for ziconotide, which was submitted on December 28, 1999, had been accepted as filed by the FDA. The FDA has agreed to a six-month review of this NDA".
  • See Review article "Keeping Up With the Cones" by Aparna Sreenivasan in Natural History 111:(1) 40-47, February 2002.
  • See also Review by Jain, K.K. (2000) "An evaluation of intrathecal ziconotide for the treatment of chronic pain" Expert Opin Investig Drugs 9:2403-2410.
  • Search for Prialt, Ziconotide or Pain or Stroke in the Atomz Search Engine box on the What's New page.

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