Evolution of Neurotoxins: From Research Modalities to Clinical Realities

Richard M. Kostrzewa1

1 Department of Pharmacology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 1.18
DOI:  10.1002/0471142301.ns0118s46
Online Posting Date:  January, 2009
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In the 1950s, the discovery of anti‐nerve growth factor, an immunotoxin stunting sympathetic neural development, signaled the advent of neurotoxins as research modalities. Other selective neurotoxins were discovered in rapid succession. In the 1960s, 6‐hydroxydopamine and 6‐hydroxydopa were shown to destroy noradrenergic and dopaminergic nerves. Excitotoxins (glutamate, aspartate, and analogs) were discovered in the 1970s. DSP‐4 [N‐(2‐chloroethyl)‐N‐ethyl‐2‐bromobenzylamine] proved to be selective for noradrenergic destruction, while 5,6‐ and 5,7‐dihydroxytryptamines were relatively selective for serotonin neurons. Additional neurotoxins were discovered, but it was MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) that predominated neurotoxicity research in the 1980s. Eventually, Clostridium botulinum neurotoxin (BoNT), discovered as a “poisonous” principle in the late 1800s, resurfaced in purified and standardized forms as a clinically useful drug. Neurotoxins represent chemical tools, useful not only for discerning neuronal mechanisms and animal modeling of neurological disorders, but also for their use in medicine and potential as treatments for medical disorders. This unit reviews the early discovery of neurotoxins, describes categories of neurotoxins, and finally characterizes their usefulness—first as research tools, and eventually as clinical therapeutic agents. Curr. Protoc. Neurosci. 46:1.18.1‐1.18.10. © 2009 by John Wiley & Sons, Inc.

Keywords: 6‐hydroxydopamine; MPTP; glutamate; botulinum neurotoxin; DSP‐4; excitotoxins

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Table of Contents

  • Neurotoxins as Research Tools
  • Discovery of Selective Neurotoxins
  • Development and Categorization of Other Neurotoxins—Research Focus
  • Endogenous Neurotoxins and Neuroprotectants
  • Confusion on the Definition of a Neurotoxin
  • Neurotoxins as Therapeutics
  • Literature Cited
  • Tables
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