Comparative Pharmacodynamics of Three Different Botulinum Toxin Type A Preparations following Repeated Intramuscular Administration in Mice

Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regula...

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Bibliographic Details
Published in:Toxins 2022-05, Vol.14 (6), p.365
Main Authors: Byun, Jaeyoon, Kwak, Seongsung, Kwon, Jin-Hee, Shin, Minhee, Lee, Dong-Kyu, Rhee, Chang-Hoon, Kang, Won-ho, Oh, Jae-Wook, Cruz, Deu John M
Format: Article
Language:English
Subjects:
Action potential
Botulinum toxin
Botulinum toxin type A
Chemical bonds
Cholinergics
Comparative analysis
compound muscle action potential
Deformation effects
digit abduction score
Dosage
Dosage and administration
Drug therapy
duration of action
Injections, Intramuscular
Manufacturing industry
Muscles
Neuromuscular diseases
Neuromuscular junctions
Neurotoxins
Paralysis
Paresis
Pharmacodynamics
Pharmacology
Proteins
repeated injection
Spasticity
Testing
Toxins
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Summary:Botulinum neurotoxin type A (BoNT/A) causes muscle paralysis by blocking cholinergic signaling at neuromuscular junctions and is widely used to temporarily correct spasticity-related disorders and deformities. The paralytic effects of BoNT/A are time-limited and require repeated injections at regular intervals to achieve long-term therapeutic benefits. Differences in the level and duration of effectivity among various BoNT/A products can be attributed to their unique manufacturing processes, formulation, and noninterchangeable potency units. Herein, we compared the pharmacodynamics of three BoNT/A formulations, i.e., Botox® (onabotulinumtoxinA), Xeomin® (incobotulinumtoxinA), and Coretox®, following repeated intramuscular (IM) injections in mice. Three IM injections of BoNT/A formulations (12 U/kg per dose), 12-weeks apart, were administered at the right gastrocnemius. Local paresis and chemodenervation efficacy were evaluated over 36 weeks using the digit abduction score (DAS) and compound muscle action potential (CMAP), respectively. One week after administration, all three BoNT/A formulations induced peak DAS and maximal reduction of CMAP amplitudes. Among the three BoNT/A formulations, only Coretox® afforded a significant increase in paretic effects and chemodenervation with a prolonged duration of action after repeated injections. These findings suggest that Coretox® may offer a better overall therapeutic performance in clinical settings.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins14060365