In:
Basic & Clinical Pharmacology & Toxicology, Wiley, Vol. 116, No. 6 ( 2015-06), p. 524-528
Abstract:
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 .
Type of Medium:
Online Resource
ISSN:
1742-7835
,
1742-7843
DOI:
10.1111/bcpt.2015.116.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2151592-X
SSG:
15,3
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