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Novel Approaches to Pain Relief Using Venom-Derived Peptides

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More than one and a half billion people worldwide suffer from moderate to severe chronic pain, the National Institute of Health estimates that pain costs health services approximately US$100 billion annually. Existing drugs for the treatment of pain are often associated with serious side effects and rapid development of tolerance, thus, there is a need for new, more selective, molecules. Ion channels play an important role throughout the pain response, from nociception via transient receptor potential (TRP) channels or ATPsensitive receptors, propagation of action potentials by voltage-sensitive sodium and potassium channels to control of the release of neurotransmitters from presynaptic terminals of dorsal root ganglion (DRG) neurones in the dorsal horn by voltage-gated calcium channels. Venoms are complex mixtures of bioactive molecules that have evolved for prey capture and defence, many of these molecules have a high selectivity for physiological processes, including modulation of ion channel function, which has not been matched by man made molecules. Thus, venoms represent an extensive source of molecules for the development of therapeutic agents. This report will review the key ion channel targets for pain relief, and venom-derived molecules and their analogues acting at these targets. We will concentrate particularly on peptides isolated from Conus venom as these represent one of the best-characterised toxin families. Our current knowledge of the molecular pharmacology of these toxin molecules will be reviewed and problems associated with using peptides as therapeutics will be discussed, along with strategies to overcome these.

Keywords: Venoms; analgesics; conotoxin; ligand-gated ion channels; pain; toxins; voltage-sensitive ion channels

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986706778742954

Affiliations: Department of Neurosciences, CMU, 1, rue Michel Servet, CH-1211 Geneva 4, Switzerland.

Publication date: November 1, 2006

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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