Botulinum neurotoxins (BoNTs), a group of
bacterial proteins that comprise a light chain
disulfide linked a heavy chain, are the most lethal biotoxins known to mankind. By inhibiting
neurotransmitter release, BoNTs cause severe neuroparalytic disease,
botulism. A series of important findings in the past 10 years which displayed the molecular targets of BoNTs and hence proposed a four-step action mechanism to explain BoNT intoxication greatly advanced the study of antibotulismic
drug. In this article, we reviewed these progresses and anti-botulismic compounds found in recent years. These compounds function due to their facilitation on
neurotransmitter release or to their interference on the binding, internalization, translocation, and
endopeptidase activity of the toxins.
Toosendanin is a
triterpenoid derivative extracted from a digestive tract-
parasiticide in
Chinese traditional medicine. Chinese scientists have found that the compound is a selective prejunctional blocker. In spite of sharing some similar action with BoNT,
toosendanin can protect
botulism animals that have been administrated with lethal doses of
BoNT/A or BoNT/B for several hours from death and make them restore normal activity. The neuromuscular junction preparations isolated from the rats that have been injected with
toosendanin tolerate
BoNT/A challenge.
Toosendanin seems to have no effect on
endopeptidase activity of BoNT, but blocks the toxin approach to its enzymatic substrate.