conotoxins therapeutic potential and application个与治疗和应用潜力.pdfVIP

Mar. Drugs 2006, 4, 119-142 Marine Drugs ISSN 1660-3397 © 2006 by MDPI /marinedrugs Special Issue on “Marine Drugs and Ion Channels” Edited by Hugo Arias Review Conotoxins: Therapeutic Potential and Application Richard T. Layer 1,* and J. Michael McIntosh 2 1 Cognetix, Inc., 421 Wakara Way, Suite 201, Salt Lake City, UT 84108, USA Phone: (801) 581-0400, Fax: (801) 581-9555, E-mail: rlayer@ 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: mcintosh.mike@ * Author to whom correspondence should be addressed. Received: 30 November 2005 / Accepted: 8 March 2006 / Published: 6 April 2006 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