Pharmacology of botulinum toxin: differences between type A preparations

Abstract

Different types of botulinum neurotoxin (BoNT) block different proteins of the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) protein complex within cholinergic nerve terminals, producing blockade of cholinergic neuromuscular and autonomic synapses. Animal studies indicate the longest duration of action for BoNT type A (BoNTA) followed by types B, F, and E. Diffusion to adjacent and remote muscles may be related to protein composition, dilutions, volume, target muscle selection, and injection technique. A review of head-to-head, randomized, controlled trials of BoNTA preparations (Botox and Dysport) suggests that Dysport tends to have higher efficacy, longer duration, and higher frequency of adverse effects. Conversion factors between the preparations varied, however, and remain controversial. In clinical settings, a Botox:Dysport conversion ratio of 1:3 may be appropriate. Animal studies suggest a conversion ratio of 1:2.5-3. When therapeutic effects between these preparations are attempting to be equalized, Dysport seems to produce more adverse effects. In mice, Botox appears to have a better safety margin than Dysport and BoNTB. In rats, diffusion margins are similar for Botox and Dysport. Jitter derived from stimulation single-fiber EMG of injected and remote muscles show no differences between Botox and Dysport. Atrophy of extrafusal muscle fibers of injected and remote muscles do not differ between the BoNTA preparations.

Current Evidence on the Unit Equivalence of Different Botulinum Neurotoxin A Formulations and Recommendations for Clinical Practice in Dermatology

“…This might not be a drug-related effect but could instead be due to variability of the clinical scoring method used, and this weakens the conclusions of Lowe and colleagues substantially. 23 According to a Phase II Food and Drug Administration trial of Dysport in the treatment of glabellar lines, a dosage of as low as 20 U is effective in most cases, supporting a unit equivalence of 2.5:1. , Karsai et al 21 , Monheit et al 24 , Ascher et al 26 , Rzany et al 29 , Ranoux et al 31 , Odergren et al 33 , Poewe et al 34 , Simonetta-Moreau et al 38 , Talarico-Filho et al 40 , Wohlfarth et al 43 IIa SR of cohort studies (CS) with homogeneity Sesardic et al 9 , Poewe, 32 Rosales et al 45 IIb Individual CS or low-quality RCT Bihari, 16 Lowe et al 22 , Brisinda et al 35 , Sampaio et al 36 , Nü Xgens and Roggenkä mper, 37 Trindade de Almeida et al 39 , Hexsel, 41 de Almeida et al 42 IIc ''Outcomes'' research Marchetti et al 17 , Heckmann and Schö n-Hupka, 25 Van den Bergh and Lison, 44 Rosales et al 45 V Expert opinion Hambleton and Pickett, 7 Rzany and Zielke, 11 Sommer et al 20 SR, systematic review; RCT, randomized controlled trial; CI, confidence interval; CS, cohort study.…”

“…This has been interpreted as showing different safety margins for the two products, but these results have not been confirmed independently. Rosales and colleagues 45 did DAS experiments in rats and found a ratio of 2.5:1 for efficacy and diffusion into the thigh muscle.…”

Administração de toxina botulínica A e a orquiectomia no tratamento da hiperplasia prostática benigna do cão

“…Em virtude da maior parte das pesquisas urológicas serem realizadas utilizando a medicação Botox ® , na dose de 100 ou 200U, e neste experimento estarmos usando a medicação Dysport ® , realizouse a equivalência dos produtos empregando a taxa de conversão de 1 unidade de Botox ® para cada 2,5 unidades de Dysport ® (ROSALES et al, 2006), promovendo, dessa maneira, o uso das mesmas doses preconizadas pelos trabalhos científicos avaliados. Entretanto, doses de 250 unidades não foram utilizadas, uma vez que seus resultados não foram significativos em estudo prévio (MOSTACHIO et al, 2012).…”

Botulism

“…El bloqueo de la liberación de neurotransmisor se produce por la escisión dependiente de zinc de 1 o 2 de los 3 componentes del núcleo del aparato de exocitosis 24,50,90,93 . La proteína del complejo SNARE afectada dependerá del tipo de BoNT; las neurotoxinas tipo B, D, F y G afectan la sinaptobrevina, los tipos A y E afectan SNAP-25, y finalmente la tipo C actúa tanto en sintaxina como en SNAP-25 50,80,81 . La acción de la toxina C no altera la formación de vesícu-las sinápticas, ni su número ni su distribución a lo largo de la membrana presináptica.…”