Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9921541 | European Journal of Pharmacology | 2005 | 7 Pages |
Abstract
Botulinum toxin is produced by Clostridium botulinum in three different molecular-weight forms: LL toxin, 900 kDa; L toxin, 500 kDa; and M toxin, 300 kDa. We isolated the M toxin, then compared its muscle-weakening efficacy with those of L+LL toxin and BOTOX® both in vitro and in vivo. The twitch tension of the mouse isolated phrenic nerve-hemidiaphragm was used for the in vitro study. For the in vivo study, grip strength was measured in the toxin-injected legs. Undesirable muscle weakening was evaluated by grip-strength measurement in the contralateral leg. Concentration-response curves for effects on the phrenic nerve-hemidiaphragm showed that M toxin was 10 times more potent than L+LL toxin. The therapeutic index in vivo was 3- to 5-times higher for M toxin than for L+LL toxin or BOTOX®, indicating a greater separation for M toxin between doses with local efficacy and systemic toxicity. These findings indicate that the M toxin preparation may have a better pharmacological profile than the conventional preparation.
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Authors
Shinji Yoneda, Masamitsu Shimazawa, Masanori Kato, Akira Nonoyama, Yasushi Torii, Hajime Nishino, Nakaba Sugimoto, Shunji Kozaki, Hideaki Hara,