Extended Project 2010-11 – Morphine Verse Snail Venom

Back in collage, seeming a long time ago now, I read a very interesting article in the New Scientist about the isolation of cone snail venom (ω-Conotoxin) for pain relief. Recently the use of Snail venom as a pain relief has re-emerged on many media sites due to an announcement at American Chemical Society so I decided to look at how things have changed in the past 4 years.

A review article by Schroeder and Lewis (2006) introduced the idea of using cone snail venom for pain relief by targeting nicotinic acetylcholine receptors (AChR).  The benefits from using snail venom compared to tradition pain relief therapies such as morphine is that it ω-Conotoxin have the potential to be fast acting, strong pain relief, not addictive and tolerance does not occur. The benefits of ω-Conotoxin are extremely useful for suffers of chronic pain being 100 times more effective than morphine.

The first FDA approved ω-Conotoxin was ziconotide (MVIIA), which had many desired benefits along with undesired side effects (Schroeder and Lewis, 2006). Ziconotide acts upon the N-type calcium channel in the pre-synaptic nerve inhibiting neuronal excitability and ability of an action potential to pass between synapses. Compared to a similar ω-Conotoxin GVIA, data has shown that GVIA has less efficacy compared to ziconotide (Schroeder and Lewis, 2006). Developments have occurred with proposed molecules to overcome the blood brain barrier but may have adverse effects on the control of blood pressure (McGivern, 2007). The second generation of N-type calcium channel blockers is AM633 which provides a wider therapeutic window which may provide fewer severe side effects (Schroeder and Lewis, 2006).

Currently, ziconotide is administered intra-spinal but developments into oral supplements may make administering ziconotide as easy as paracetamol. Problems arise with ω-Conotoxin due to its protein structure where it is naturally denatured and metabolised through the human digestive system. Professor David Craik, University of Queensland is currently researching new possibilities for administration of ziconotide and the news released on March 16th 2014 was the development of 5 promising compounds which derive from modifications of the ω-Conotoxin which have promising results in rat models.

Reference List

McGivern, J.G. (2007) Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatric Disease and Treatment, 3(1), pp. 69-85.

Schroeder, C.I.; and Lewis, R.J. (2006) ω-Conotoxin GVIA, MVIIA and CVID: SAR and Clinical Potential. Marine Drugs, 4(3), pp. 193-214.




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