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. 2023 Jul 1;102(S1):e32372.
doi: 10.1097/MD.0000000000032372.

Botox (onabotulinumtoxinA) mechanism of action

Mitchell F Brin  1   2 , Rami Burstein  3
Affiliations

Botox (onabotulinumtoxinA) mechanism of action

Mitchell F Brin et al. Medicine (Baltimore). .

Abstract

Studies in the 1920s found that botulinum neurotoxin type A (BoNT/A) inhibited the activity of motor and parasympathetic nerve endings, confirmed several decades later to be due to decreased acetylcholine release. The 1970s were marked by studies of cellular mechanisms aided by use of neutralizing antibodies as pharmacologic tools: BoNT/A disappeared from accessibility to neutralizing antibodies within minutes, although it took several hours for onset of muscle weakness. The multi-step mechanism was experimentally confirmed and is now recognized to consist broadly of binding to nerve terminals, internalization, and lysis or cleavage of a protein (SNAP-25: synaptosomal associated protein-25 kDa) that is part of the SNARE (Soluble NSF Attachment protein REceptor) complex needed for synaptic vesicle docking and fusion. Clinical use of the BoNT/A product onabotulinumtoxinA was based on its ability to reduce muscle contractions via inhibition of acetylcholine from motor terminals. Sensory mechanisms of onabotulinumtoxinA have now been identified, supporting its successful treatment of chronic migraine and urgency in overactive bladder. Exploration into migraine mechanisms led to anatomical studies documenting pain fibers that send axons through sutures of the skull to outside the head-a potential route by which extracranial injections could affect intracranial processes. Several clinical studies have also identified benefits of onabotulinumtoxinA in major depression, which have been attributed to central responses induced by feedback from facial muscle and skin movement. Overall, the history of BoNT/A is distinguished by basic science studies that stimulated clinical use and, conversely, clinical observations that spurred basic research into novel mechanisms of action.

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Conflict of interest statement

This manuscript was funded by AbbVie. AbbVie was involved in the manuscript concept and participated in writing, reviewing, and approval of the final version. No honoraria or payments were made for authorship. MF Brin is a full-time employee of AbbVie and holds stock in the company. R Burstein received research funding from Allergan and AbbVie. He is also a consultant to these companies.

Figures

Figure 1.
Figure 1.
Botulinum neurotoxin type A (BoNT/A) mechanism of action. Events at the synapse are shown in the absence (top panel) and presence (bottom panel) of BoNT/A.
Figure 2.
Figure 2.
Drs. David Dodick, Aubrey Adams, Mitchell Brin, and Rami Burstein (left to right) in Westport, Ireland.
See this image and copyright information in PMC

References

    1. Kerner J. Neue Beobachtungen uber die in Wurttemberg so haufig vorfallenden todlichen Vergiftungen durch den Genuss geraucherter Wurste. Tubingen: Osiander. 1820.
    1. Van Ermengem EP. Uber einen neuen anaeroben Bacillus und seine Beziehung zum Botulismus. Z Hyg Infektionskrankh. 1897;26:1–56. - PubMed
    1. Tchitchikine A. Essai d’immunisation par la voie gastrointestinale contre la toxine botulique [letter]. Ann Inst Pasteur XIX. 1905;24:335.
    1. Dickson EC, Shevky E. Botulism. Studies on the manner in which the toxin of clostridium botulinum acts upon the body: II. The effect upon the voluntary nervous system. J Exp Med. 1923;38:327–46. - PMC - PubMed
    1. Dickson EC, Shevky R. Botulism. Studies on the manner in which the toxin of clostridium botulinum acts upon the body: I. The effect upon the autonomic nervous system. J Exp Med. 1923;37:711–31. - PMC - PubMed

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