title: Pharmacology of botulinum neurotoxin serotype A.
abstract: OBJECTIVE
  An historical perspective on the discovery and development of botulinum neurotoxin for commercial use, the differences between various botulinum toxin serotypes and commercially available products, and the structure, mechanism of action, pharmacologic effects, and immunogenicity of botulinum toxin type A are discussed.
  
  
  CONCLUSIONS
  Botulinum toxin was discovered several centuries ago, but its medical uses have only recently been explored. There are several botulinum toxin serotypes that differ in composition and molecular weight. The protein component of the macromolecular structure that has pharmacologic activity requires enzymatic activation, and the required enzyme varies by serotype. All serotypes interfere with muscle contraction by inhibiting acetylcholine release into the synaptic space at the neuromuscular junction, although the intracellular target varies by serotype. An antinociceptive effect may be mediated by a similar mechanism involving inhibition of pain mediator release. The effects of botulinum toxin usually are only temporary because collateral axonal sprouts that can release acetylcholine develop. The protein load and immunogenicity vary among the commercially available botulinum toxin products. The smallest protein load and longest dosing interval should be used to minimize resistance. Alternating among different serotypes is not an effective strategy for preventing or overcoming resistance because cross-resistance can occur.
  
  
  CONCLUSIONS
  All botulinum toxin serotypes and products cause temporary muscle paralysis, yet vary in important ways that may affect their clinical use.
authors.affiliation: Diamond Headache Clinic Inpatient Unit, St. Joseph Hospital, 2900 North Lake Shore Drive, Chicago, IL 60657, USA. rwenz@hotmail.com
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wenzel
mesh_terms: D019274:Botulinum Toxins, Type A / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry; D009626:Terminology as Topic; D014481:United States
chemical_list: D004364:Pharmaceutical Preparations; D019274:Botulinum Toxins, Type A