W-conotoxin MVIIA

In vertebrates, the spectrum of w-conotoxin targets is dependent not only on the species of animal being studied, but on the w-conotoxin being used. In chicks and frogs all synapses tested are almost completely inhibited by w-conotoxin GVIA, while in rodents, w-conotoxin GVIA does not inhibit the neuromuscular synapse, and only a fraction of CNS synapses tested are blocked. In contrast, w-conotoxin MVIIA acts much more reversibly and with a much reduced affinity for many amphibian, and some mammalian, synapses. 

Fig. 23. w-conotoxins MVIIA and MVIIC. The three disulfide bonds that make up the cystine-knot motif are indicated, as are the four loops in the peptide backbone. Note the small difference in the orientation of loops 2 and 4 between the two molecules. 

The uKxmotoxins have attracted much recent interest owing to their potential application in the treatment of chronic pain, exemplified by the success of w-conotoxin MVIIA (Ziconotide) in phase III clinical trials initiated by the US pharmaceutical company Neurex. Ziconotide also has potential applications in other conditions associated with regulation of calcium channels. As with all peptides, though, bioavailability considerations and possible side-effects mean that the mode of delivery needs careful consideration. In the current pain trials, an infusion pump is used for delivery of peptide direct into... 

There is a great pharmaceutical interest in w-conotoxins such as w-conotoxin MVIIA that selectively inhibit N-type calcium channels. The N-type VSCCs play integral roles in the release of neurotransmitters in the spinal cord, the inhibition of which causes attenuation of neuropathic pain response with subjects less prone to tolerance when compared to morphine. ... 

The ability of conotoxins to selectively block ion channels and neuronal receptors has led to their development into therapeutic agents. So far, most conotoxin applications as therapeutics have been concentrated on the treatment of different forms of pain. The first drug of marine origin is based on the w-conotoxin MVIIA for the treatment of chronic pain (see helow). Other therapeutic applications of conotoxins include treatment of schizophrenia, epilepsy, neuromuscular disorders, certain types of cancer, urinary dysfunction, Parkinson s disease, Alzheimer s disease, stroke, and related hrain injuries. Other uses include muscle relaxants, anesthetics, and antiseizure compounds. As the demand for new painkillers and other neuropharmacological agents is expected to increase, the value of the discovery and testing of new conotoxins is expected to continue to expand. 

Besides their therapeutic applications, conotoxins have exhibited great potential for the development of neurological probes. Conotoxins are currently being used in hundreds of research laboratories for a wide variety of physiological investigations. Some conotoxins have become well-established neurobiological tools. They can also be used as antagonists of specific subtypes in functional studies for example, w-conotoxin MVIIA is used as a specific N-type calcium channel blocker. Conotoxins are also utilized in research to provide information on the role and distribution of different receptor subtypes. Undoubtedly, these research applications will continue to expand. 

Olivera, B.M. (2000) w-Conotoxin MVIIA from marine snail venom to analgesic drug, in Drugs from the Sea (ed. N. Fusetani), Karger, pp. 74-85. 

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