Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-06-13T19:54:58.541Z Has data issue: false hasContentIssue false

Chapter 3 - Pharmacology of Botulinum Toxin Therapy

Published online by Cambridge University Press:  02 November 2023

By
Daniel Truong ,
Frank Xing  and
Mark Hallett
Edited by
Daniel Truong ,
Dirk Dressler ,
Mark Hallett ,
Christopher Zachary  and
Mayank Pathak
Daniel Truong
Affiliation:
University of California, Riverside
Dirk Dressler
Affiliation:
Hannover Medical School
Mark Hallett
Affiliation:
National Institutes of Health (NIH)
Christopher Zachary
Affiliation:
University of California, Irvine
Mayank Pathak
Affiliation:
Truong Neuroscience Institute
Get access

Summary

Botulinum neurotoxins (BoNTs) are protins derived from the bacterium Clostridium botulinum. Nine serotypes are known; seroptypes A and B have been formulated for clinical use. BoNTs cleave one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) proteins: vesicle-associated membrane protein (VAMP), synaptosomal-associated protein 25 (SNAP-25), or syntaxin. Upon entry into the synaptic terminal, BoNT inhibits the exocytosis of neurotransmitter containing synaptic vesicles. Cliical effects begin developing within a week after injection into skeletal muscle, then wear off after 2–4 months, requiring repeat injection. Neutralizing antibodies may develop, reducing clinical effects. Newer toxin preparations under development are listed in a table.

Keywords

Botuinum neurotoxinserotypeBoNTClostridium botulinumSNARE proteinVAMP proteinStyntaxinneutralizing antibodiesletibotulinumtoxinABotulaxbotulinumtoxinEInnotox
Type
Chapter
Information
Manual of Botulinum Toxin Therapy , pp. 13 - 17
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Brin, MF, Boodhoo, TI, Pogoda, JM et al. (2009). Safety and tolerability of onabotulinumtoxinA in the treatment of facial lines: a meta-analysis of individual patient data from global clinical registration studies in 1678 participants. J Am Acad Dermatol, 61(6), 911–61. https://doi.org/10.1016/j.jaad.2009.06.040CrossRefGoogle Scholar
Brin, MF, Comella, CL, Jankovic, J, Lai, F, Naumann, M (2008). Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay. Move Disord, 23(10), 1353–60. https://doi.org/10.1002/mds.22157CrossRefGoogle ScholarPubMed
Chen, S (2012). Clinical uses of botulinum neurotoxins: current indications, limitations and future developments. Toxins, 4(10), 913–39. https://doi.org/10.3390/toxins4100913CrossRefGoogle ScholarPubMed
Chertow, DS, Tan, ET, Maslanka, SE et al (2006). Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation. JAMA, 296(20), 2476–9. https://doi.org/10.1001/jama.296.20.2476Google Scholar
Choudhury, S, Baker, MR, Chatterjee, S, Kumar, H (2021). Botulinum toxin: an update on pharmacology and newer products in development. Toxins, 13(1), 58. https://doi.org/10.3390/toxins13010058CrossRefGoogle ScholarPubMed
de Paiva, A, Meunier, FA, Molgó, J, Aoki, KR, Dolly, JO (1999). Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A, 96(6), 3200–5. https://doi.org/10.1073/pnas.96.6.3200CrossRefGoogle ScholarPubMed
Donald, S, Elliott, M, Gray, B et al. (2018). A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo. Pharmacol Res Perspect, 6(6), e00446. https://doi.org/10.1002/prp2.446CrossRefGoogle ScholarPubMed
Dong, M, Yeh, F, Tepp, WH et al. (2006). SV2 is the protein receptor for botulinum neurotoxin A. Science, 312(5773), 592–6. https://doi.org/10.1126/science.1123654CrossRefGoogle ScholarPubMed
Dressler, D, Benecke, R (2003). Autonomic side effects of botulinum toxin type B treatment of cervical dystonia and hyperhidrosis. Eur Neurol, 49(1), 34–8. https://doi.org/10.1159/000067023Google Scholar
Durham, PL, Cady, R, Cady, R (2004). Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache, 44(1), 33–5. https://doi.org/10.1111/j.1526-4610.2004.04007.xGoogle Scholar
Foran, PG. Mohammed, N, Lisk, GO et al. (2003). Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons. J Biol Chem, 278(2), 1363–71. https://doi.org/10.1074/jbc.M209821200CrossRefGoogle Scholar
Gelb, DJ, Yoshimura, DM, Olney, RK, Lowenstein, DH, Aminoff, MJ (1991). Change in pattern of muscle activity following botulinum toxin injections for torticollis. Ann Neurol, 29(4), 370–6. https://doi.org/10.1002/ana.410290407CrossRefGoogle ScholarPubMed
Kutschenko, A, Reinert, M-C, Krez, N, Liebetanz, D, Rummel, A (2017). BoNT/AB hybrid maintains similar duration of paresis as BoNT/A wild-type in murine running wheel assay. Neurotoxicology, 59, 1–8. https://doi.org/10.1016/j.neuro.2016.12.008CrossRefGoogle ScholarPubMed
Lungu, C, Karp, BI, Alter, K, Zolbrod, R, Hallett, M (2011). Long-term follow-up of botulinum toxin therapy for focal hand dystonia: outcome at 10 years or more. Mov Disord, 26(4), 750–3. https://doi.org/10.1002/mds.23504Google Scholar
Montal, M (2009). Translocation of botulinum neurotoxin light chain protease by the heavy chain protein-conducting channel. Toxicon, 54(5), 565–9. https://doi.org/10.1016/j.toxicon.2008.11.018Google Scholar
Moore, AP, Naumann, M (2003). Handbook of Botulinum Toxin Treatment, 2nd ed. Malden, MA: Blackwell Science.Google Scholar
Naumann, M, Jankovic, J (2004). Safety of botulinum toxin type A: a systematic review and meta-analysis. CurrMed Res Opin, 20(7), 981–90. https://doi.org/10.1185/030079904125003962Google Scholar
Purkiss, J, Welch, M, Doward, S, Foster, K (2000). Capsaicin-stimulated release of substance P from cultured dorsal root ganglion neurons: involvement of two distinct mechanisms. Biochem Pharmacol, 59(11), 1403–6. https://doi.org/10.1016/s0006–2952(00)00260-4CrossRefGoogle ScholarPubMed
Rasetti-Escargueil, C, Popoff, MR (2020). Engineering botulinum neurotoxins for enhanced therapeutic applications and vaccine development. Toxins, 13(1). https://doi.org/10.3390/toxins13010001Google Scholar
Simpson, LL (1981). The origin, structure, and pharmacological activity of botulinum toxin. Pharmacol Rev, 33(3), 155–88.Google ScholarPubMed
Tighe, AP, Schiavo, G (2013). Botulinum neurotoxins: mechanism of action. Toxicon, 67, 87–93. https://doi.org/10.1016/j.toxicon.2012.11.011CrossRefGoogle ScholarPubMed
Zhang, S. Masuyer, G, Zhang, J et al. (2017). Identification and characterization of a novel botulinum neurotoxin. Nat Commun, 8, 14130. https://doi.org/10.1038/ncomms14130CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×