scholarly journals The Pharmacology of Botulinum Toxin Type A

2022 ◽  
Author(s):  
Anna V. Reznik
Keyword(s):  
Botulinum Neurotoxin ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Zinc Metabolism ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Factors Affecting ◽  
Body Distribution ◽  
Treatment Safety

The aim of this chapter is to structure current information clarifying the most disputable issues of botulinum neurotoxin type A (BoNT/A) pharmacology after systemic (botulism) impact and local medical application. Botulinum neurotoxin (BoNT) pharmacological features evaluated open ways to study factors affecting its biological activity: to extend/shorten its effect duration, to increase/decrease BoNT sensitivity in specific patient populations. The chapter presents unique molecular mechanisms underlying BoNT/A pharmacokinetics and pharmacodynamics: entering the body, distribution, receptor binding, translocation, mediator release suppression, zinc metabolism as well as factors affecting body sensitivity to BoNT at each of those stages. The specific biological effects of BoNT/A, which may underlie its analgesic, anticancer and anti-inflammatory effects, are described. Botulinum neurotoxin pharmacokinetics and pharmacodynamics features discussed herein represent significant clinical relevance since they determine botulinum treatment safety and effectiveness. And also they open ways to develop both BoNT-based therapies and anti-botulinic agents.

scholarly journals A Moving Residual Limb: Botulinum Toxin to the Rescue

2020 ◽  
Vol 11 (1) ◽  
pp. 34-37 ◽  
Author(s):  
Marie-Michèle Briand ◽  
Mathieu Boudier-Réveret ◽  
Xavier Rodrigue ◽  
Geneviève Sirois ◽  
Min Cheol Chang
Keyword(s):  
Botulinum Toxin ◽  
Botulinum Neurotoxin ◽  
Rare Complication ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Botulinum Toxin Type ◽  
Residual Limb ◽  
Satisfaction Level ◽  
Botulinum Neurotoxin Type A ◽  
Standardized Treatment

AbstractMovement disorders post-amputation are a rare complication and can manifest as the jumping stump phenomenon, a form of peripheral myoclonus. The pathophysiology remains unknown and there is currently no standardized treatment. We describe the case of a 57-year-old male with unremitting stump myoclonus, starting one month after transtibial amputation, in his residual limb without associated phantom or neurological pain. The consequence of the myoclonus was a reduction in prosthetic wearing time. Failure to respond to oral medication led us to attempt the use of botulinum neurotoxin Type A injections in the involved muscles of the residual limb. Injection trials, over a two-year period, resulted in an improvement of movement disorder, an increased prosthetic wearing time and a higher satisfaction level of the patient. Injection of botulinum toxin type A should be considered as an alternative treatment for stump myoclonus to improve prosthetic wearing time and comfort.

scholarly journals Mechanisms of Botulinum Toxin Type A Action on Pain

Toxins ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 459 ◽  
Author(s):  
Matak ◽  
Bölcskei ◽  
Bach-Rojecky ◽  
Helyes
Keyword(s):  
Botulinum Toxin ◽  
Pain Therapy ◽  
Molecular Mechanisms ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Botulinum Toxin Type ◽  
Pharmacokinetic Parameters ◽  
Special Importance ◽  
Sustained Effect ◽  
Nociceptive Pathway

Already a well-established treatment for different autonomic and movement disorders, the use of botulinum toxin type A (BoNT/A) in pain conditions is now continuously expanding. Currently, the only approved use of BoNT/A in relation to pain is the treatment of chronic migraines. However, controlled clinical studies show promising results in neuropathic and other chronic pain disorders. In comparison with other conventional and non-conventional analgesic drugs, the greatest advantages of BoNT/A use are its sustained effect after a single application and its safety. Its efficacy in certain therapy-resistant pain conditions is of special importance. Novel results in recent years has led to a better understanding of its actions, although further experimental and clinical research is warranted. Here, we summarize the effects contributing to these advantageous properties of BoNT/A in pain therapy, specific actions along the nociceptive pathway, consequences of its central activities, the molecular mechanisms of actions in neurons, and general pharmacokinetic parameters.

Synergic Effect of Botulinum Toxin Type-A and Triamcinolone Alleviates Scar Pruritus By Modulating Epidermal Hyperinnervation: A Preliminary Report

2021 ◽  
Author(s):  
Shu-Hung Huang ◽  
Kuo-Wei Wu ◽  
Jing-Jou Lo ◽  
Sheng-Hua Wu
Keyword(s):  
Botulinum Toxin ◽  
Clinical Efficacy ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Botulinum Toxin Type ◽  
Nerve Fibers ◽  
Therapeutic Interventions ◽  
Transient Receptor Potential Vanilloid

Abstract Background Patients often experience scar-related pruritus, which negatively affects quality of life. Triamcinolone acetonide (TAC) is widely used to treat pathological scars, and botulinum toxin type-A (BTX-A) reportedly improves scarring and associated discomfort. Objectives To investigate the clinical efficacy of the combined TAC and BTX-A (TAC/BTX-A) in reducing scar itch and their potential mechanisms via animal model. Methods In a clinical study, each scar on a patient was divided into 2 equal parts, with one part receiving TAC/BTX-A and the other TAC alone. Therapeutic interventions were administered over 3 sessions, each 4 weeks apart. Itch intensity was measured using visual analogue scale before each therapeutic intervention (V1, V2, V3) and 4 weeks after the last intervention (V4). In a rat model, rats were allocated into 5 groups: control, untreated burn, TAC, BTX-A, and TAC/BTX-A groups. We evaluated alloknesis in the right hind paw and analyzed possible molecular mechanisms. Results In humans, TAC/BTX-A significantly reduced scar itch compared with TAC alone at V4 (p = 0.04). In rats, post-burn itch was mitigated at 4 weeks after treatment with TAC, BTX-A, and TAC/BTX-A (p = 0.03, p = 0.0054, and p = 0.0053, respectively). TAC/BTX-A significantly decreased the density of intraepidermal nerve fibers post-burn relative to the untreated burn (p = 0.0008). TAC/BTX-A downregulated the expressions of nerve growth factor (NGF) and protein transient receptor potential vanilloid subtype 1 (TRPV1). Conclusions TAC/BTX-A therapy exhibited enhanced and sustained clinical efficacy in relieving scar itch, possibly via modulating epidermal innervation and TRPV1 expression.

Multiple forms of SNARE complexes in exocytosis from chromaffin cells: effects of Ca2+, MgATP and botulinum toxin type A

2002 ◽  
Vol 115 (3) ◽  
pp. 667-673 ◽  
Author(s):  
Gary W. Lawrence ◽  
J. Oliver Dolly
Keyword(s):  
Chromaffin Cells ◽  
Botulinum Neurotoxin ◽  
Early Stage ◽  
Botulinum Toxin Type A ◽  
Type A ◽  
Snare Complex ◽  
Relative Molecular Mass ◽  
Botulinum Neurotoxin A ◽  
Sds Page ◽  
Wide Range

The changes that SNAREs undergo during exocytosis were studied in permeabilised chromaffin cells treated with Ca2+, MgATP or botulinum neurotoxin A. High-resolution 2D SDS-PAGE revealed multiple SDS-resistant SNARE complexes having a wide range of sizes and in which SNAP-25 and syntaxin predominate over synaptobrevin. Their formation increased upon Ca2+-stimulated exocytosis; notably, the 2D protocol proved much superior to 1D SDS-PAGE for the detection of large complexes and revealed that for forms with relative molecular mass greater than 100,000 stimulated induction was more significant than for smaller species. MgATP enhanced Ca2+-triggered catecholamine release but reduced the content of complexes. By contrast, botulinum neurotoxin type A inhibited exocytosis and altered the stoichiometry of the SNAP-25:syntaxin binary association, without lowering its abundance. The individual SNAREs were protected against trypsin proteolysis to varying extents in binary and ternary complexes of different sizes, suggestive of distinct folding intermediates. Our data suggest that Ca2+ triggers an early stage of SNARE complex formation causing an accumulation of partially folded intermediates, especially of binary forms, as well as their maturation into smaller, more protease resistant states. In addition, botulinum neurotoxin A inhibits exocytosis by perturbing the syntaxin:SNAP-25 ratio in binary intermediates.

Effects of intra-articular botulinum toxin type A (Botox®) in dogs with chronic osteoarthritis

2010 ◽  
Vol 23 (04) ◽  
pp. 254-258 ◽  
Author(s):  
J. L. Wheeler ◽  
S. W. Petersen ◽  
H. S. Hadley
Keyword(s):  
Botulinum Neurotoxin ◽  
Botulinum Toxin Type A ◽  
Hip Osteoarthritis ◽  
Type A ◽  
Botulinum Toxin Type ◽  
Ground Reaction Forces ◽  
Vertical Force ◽  
Multimodal Approach ◽  
Botulinum Neurotoxin Type A ◽  
Reaction Forces

Summary Objectives: To evaluate the effects of intra-articular botulinum neurotoxin type A (BoNT/A) in dogs with chronic osteo-arthritis. Methods: Client-owned dogs with lameness and discomfort attributed to unilateral elbow or hip osteoarthritis were eligible for inclusion (n = 5). All dogs had BoNT/A (25 units) administered to the affected joint (2 elbows, 3 hips). Dogs were evaluated by pressure platform gait analysis before and at two, four, eight, and 12 weeks post-injection, and by client perception of outcome. Results: In experimental limbs, ground reaction forces (peak vertical force and vertical impulse) consistently improved for a variable period of time following intra-articular BoNT/A therapy. These changes were not, however, observed in the contralateral limbs, in which values remained relatively unchanged or decreased. Four out of five owners reported at least some improvement in their dog’s condition following treatment. Clinical significance: A multimodal approach with the intra-articular administration of BoNT/A may be an option for osteoarthritis patients that are unresponsive to medical management and unable to undergo surgery. However, the findings of this study are preliminary and must be verified by further investigation.

scholarly journals Treatment of Immature Scars with Botulinum Toxin

2020 ◽  
pp. 219-226
Author(s):  
Alexandra Chambers
Keyword(s):  
Clinical Practice ◽  
Botulinum Toxin ◽  
Botulinum Neurotoxin ◽  
Biological Effects ◽  
Muscle Tension ◽  
Type A ◽  
Inhibitory Effects ◽  
Botulinum Neurotoxin Type A ◽  
Tissue Healing ◽  
Therapeutic Choice

AbstractUsing Botulinum neurotoxin type A (BoNTA) has yielded promising results in the treatment of immature scars. The biological effects of the toxin on tissue healing appear to be complex and multidimensional and still require additional research. Nevertheless, it is clear that not only does BoNTA reduce muscle tension at the edges of wounds, but it also provides anti-inflammatory effects, promotes angiogenesis and healing, and exerts mediatory or inhibitory effects on a variety of cells. In clinical practice, this pluripotency of BoNTA has been recognized as a therapeutic choice for both prophylaxis and treatment of excessive scarring.

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