Title: Evaluation of toosendanin as a botulinum neurotoxin antagonist

Authors: Michael Adler, James D. Nicholson

Addresses: Neurobehavioral Toxicology Branch, Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, USA. ' Neurobehavioral Toxicology Branch, Analytical Toxicology Division, US Army Medical Research Institute of Chemical Defense, 3100 Ricketts Point Road, Aberdeen Proving Ground, MD 21010-5400, USA

Abstract: Toosendanin (TSN), a tetranortriterpenoid compound from the plant Melia toosendan, has been reported to protect rats and non-human primates from the lethal actions of botulinum neurotoxin A (BoNT/A). TSN was tested in isolated mouse phrenic nerve-hemidiaphragm preparations against BoNT serotypes A, B and E. When added prior to toxin, TSN was found to delay the onset of muscle paralysis with all 3 BoNT serotypes. TSN had little or no effect on BoNT-induced muscle paralysis when applied 30 min after BoNT. It is suggested that the antagonist activity of TSN may result from inhibition of BoNT translocation.

Keywords: toosendanin; triterpenoid; twitch tension; mouse diaphragm muscle; botulinum neurotoxins; BoNT; botulinum antagonist; acetylcholine; botulism; muscle paralysis.

DOI: 10.1504/TBJ.2008.026469

The Botulinum Journal, 2008 Vol.1 No.2, pp.208 - 218

Published online: 16 Jun 2009 *

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