Conotoxins: Therapeutic Potential and Application |
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Authors: | Richard T. Layer J. Michael McIntosh |
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Affiliation: | 1.Cognetix, Inc., 421 Wakara Way, Suite 201, Salt Lake City, UT 84108, USA, Phone: (801) 581-0400, Fax: (801) 581-9555, E-mail: ;2.Department of Psychiatry and Department of Biology, University of Utah, 257 S. 1400 E., Salt Lake City, UT 84112, USA, Phone: (801) 585-3622, Fax: (801) 585-5010, E-mail: |
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Abstract: | The pharmacological variety of conotoxins, diverse peptides found in the venoms of marine cone snails, is well recognized. Venoms from each of the estimated 500 species of cone snails contain 50 to 200 distinct biologically active peptides. Most conotoxins characterized to date target receptors and ion channels of excitable tissues, such as ligand-gated nicotinic acetylcholine, N-methyl-D-aspartate, and type 3 serotonin receptors, as well as voltage-gated calcium, sodium, and potassium channels, and G-protein-coupled receptors including α-adrenergic, neurotensin, and vasopressin receptors, and the norepinephrine transporter. Several conotoxins have shown promise in preclinical models of pain, convulsive disorders, stroke, neuromuscular block, and cardioprotection. The pharmacological selectivity of the conotoxins, coupled with the safety and efficacy demonstrated in preclinical models, has led to their investigation as human therapeutic agents. In the following review, we will survey the pharmacology and therapeutic rationale of those conotoxins with potential clinical application, and discuss the unique challenges that each will face in the course of their transition from venom component to human therapeutic. |
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Keywords: | conotoxin conopeptide cone snail venom analgesia |
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