Toxicon 59 (2012) 433

e at SciVerse ScienceDirect

Contents lists availabl

Toxicon

journal homepage: www.elsevier .com/locate/ toxicon

From venoms to drugs: Introduction

Venoms are complex mixtures of peptides and proteins,and their effects in vivo can also be complex becausedifferent constituents have different actions and becausesome of the components can act synergistically withothers. Individual toxins, however, often have very specificpharmacological effects. Toxins have been invaluable toolsfor probing physiological processes, and toxins can alsoprovide leads for drug discovery and development. ThisSpecial Issue brings together several reviews that discussthe role that toxins have played and continue to play in thesearch for better therapeutic agents.

The potential for naturally occurring toxic molecules formedicinal uses was probably first revealed in the 1940swith the introduction of tubocurarine as a muscle relaxantfor use in surgery along with general anaesthetic agents.Tubocurarine is a plant alkaloid that is the active ingredientof some South American arrow poisons. It blocks nicotinicacetylcholine receptors at neuromuscular junctions and,hence, causes paralysis. Tubocurarine and related naturallyoccurring alkaloids acted as the starting point for thedesign of synthetic analogues with improved pharmaco-kinetic properties and fewer autonomic side effects.

Since then, the potential for venom components wasillustrated by the development of the ACE inhibitors fromthe leads provided by bradykinin potentiating peptidesisolated from venom of the South American pit viperBothrops jararaca. Work continues to explore the thera-peutic potential of similar venom peptides, as discussed inthe article by Camargo and colleagues in this volume.

Other snake venoms affect blood coagulation and manyactive components have been isolated and studied fortheir actions on different parts of the coagulation cascade.Components that reduced platelet aggregation attractedattention, and two disintegrins, barbourin (from the SouthEastern pygmy rattlesnake Sistrurus miliarius barbouri) andechistatin (from the sawscaled viper, Echis carinatus),provided the leads for two new therapeutic agents, eptifi-batide and tirofiban, respectively. They are used to preventmyocardial infarction in patients with unstable angina.

0041-0101/$ – see front matter � 2011 Elsevier Ltd. All rights reserved.doi:10.1016/j.toxicon.2011.09.016

Snakes are not the only source of venoms that haveattracted the attention of drug developers. There is muchinterest in the potential of components from venomsof various species of Conus marine snails. This is exem-plified by the successful introduction of ziconotide foruse in patients with intractable pain. Ziconotide is thesynthetic version of u-conotoxin MVIIA from Conusmagus which is a specific blocker of N-type Ca2þ chan-nels. When administered intrathecally, ziconotide actson neurons in the spinal cord responsible for trans-mitting pain stimuli to reduce the amount of neuro-transmitter released from nerve endings and thereforereduce the strength of the signal. The therapeuticpotential of other conopeptides is discussed in the articleby Lewis in this volume.

These are just a few examples of research on toxins withtherapeutic potential. More details and other examples arecontained in this volume. We hope that the opportunitiesfor finding novel therapeutic agents from venoms andtoxins will become more widely recognised and lead tofurther contributions to extending and improving the rangeof drugs at our disposal.

Alan L. Harvey*Strathclyde Institute of Pharmacy and Biomedical Sciences,University of Strathclyde, 161 Cathedral Street, Glasgow G4

0RE, UK

Reto StöcklinAtheris Laboratories, Case Postale 314, CH-1233 Bernex,

Geneva, Switzerland

� Corresponding author. Tel.: þ44 (0) 141 553 4155; fax:þ44 (0) 141 552 8376.

E-mail addresses: a.l.harvey@strath.ac.uk,toxicon@strath.ac.uk (A.L. Harvey)

22 July 2011Available online 21 December 2011