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Comparison of Systemic Toxicity between Botulinum Toxin Subtypes A1 and A2 in Mice and Rats
Author(s) -
Torii Yasushi,
Goto Yoshitaka,
Nakahira Shinji,
Kozaki Shunji,
Kaji Ryuji,
Ginnaga Akihiro
Publication year - 2015
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12351
Subject(s) - toxin , neurotoxin , progenitor cell , toxicity , pharmacology , progenitor , median lethal dose , lethal dose , medicine , chemistry , biology , toxicology , biochemistry , stem cell , genetics
The adverse events caused by botulinum toxin type A (subtype A1) product, thought to be after‐effects of toxin diffusion after high‐dose administration, have become serious issues. A preparation showing less diffusion in the body than existing drugs has been sought. We have attempted to produce neurotoxin derived from subtype A2 (A2 NTX ) with an amino acid sequence different from that of neurotoxin derived from subtype A1 (A1 NTX ). In this study, to investigate whether A2 NTX has the potential to resolve these issues, we compared the safety of A2 NTX , a progenitor toxin derived from subtype A1 (A1 progenitor toxin) and A1 NTX employing the intramuscular lethal dose 50% (im LD 50 ) in mice and rats and the compound muscle action potential ( CMAP ) in rats. Mouse im LD 50 values for A1 progenitor toxin and A2 NTX were 93 and 166 U/kg, respectively, and the rat im LD 50 values were 117 and 153 U/kg, respectively. In the rat CMAP test, the dose on the contralateral side, which caused a 50% reduction in the CMAP amplitude, that is, CMAP ‐ TD 50 , was calculated as 19.0, 16.6 and 28.7 U/kg for A1 progenitor toxin, A1 NTX and A2 NTX , respectively. The results indicate that A2 NTX is safer than A1 progenitor toxin and A1 NTX .