Botulinum toxin: Chemistry, pharmacology, toxicity, and immunology

Mitchell F. Brin

Research output: Contribution to journalArticlepeer-review

432 Scopus citations

Abstract

The seven serotypes of botulinum toxin (BTX) produced by Clostridium botulinum exert their paralytic effect by inhibiting acetylcholine release at the neuromuscular junction. Each of these zinc endopeptidases cleaves one or more proteins involved in vesicle transport and membrane fusion. The extent of paralysis depends on both doses and volume; the duration of paralysis is further dependent on the serotype employed. Restoration of neuromuscular function follows axon terminal sprouting. The two major commercial preparations of BTX-A appear to differ in their relative potencies, despite a common unit labeling system. Adverse effects are a consequence of the drug's mechanism of action, and can usually be tolerated or mitigated through dosing changes. Patients who are pregnant or lactating, or who have a neuromuscular disease, may not be appropriate candidates for BTX therapy. Development of resistance to BTX-A therapy, characterized by absence of any beneficial effect and by lack ol muscle atrophy following the injection, is an important clinical issue. The incidence of antibody-mediated resistance, as determined by the mouse lethality assay, is reported between 3% and 10%. Use of the smallest possible effective dose and longer treatement intervals may reduce the likelihood of antibody development. Other serotypes may benefit those who have developed antibody resistance.

Original languageEnglish
Pages (from-to)S146-S168
JournalMuscle and Nerve
Volume20
Issue numberSUPPL. 6
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Adverse effects
  • Antibody-mediated resistance
  • Botulinum toxin (BTX)
  • Mouse lethality assay
  • Zinc endopeptidase

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