CHAPTER 9: Case Study 1: Development of the Analgesic Drugs Prialt^® and Xen2174 from Cone Snail Venoms

Cone snail venoms are a rich source of small, structurally constrained peptides (conotoxins) that are widely used as research tools and as a source of promising leads to potential therapies. At least 15 pharmacological classes of conotoxins have been characterized, including clinically evaluated ω-conotoxins that inhibit the voltage-gated calcium channel Ca_v2.2 and χ-conopeptides that inhibit the noradrenaline transporter. The ω-conotoxins isolated from piscivorous snails and χ-conopeptides from molluscivorous snails produce analgesia when administered intrathecally in rodent models of neuropathic pain, by either directly or indirectly inhibiting Ca_v2.2. Open label studies showed that intrathecal ω-MVIIA (Prialt®), ω-CVID (Leconitide) and χ-Xen2174 reduced pain scores in cancer patients suffering severe chronic pain. This review compares and contrasts these two classes of venom peptide and the pain pathways they inhibit.