In particular, while many of the steps in the action of the BoNTs are well understood, the factors underlying the timing of these steps are less so. The clinical effects are certainly well known, but a detailed explanation of all the phenomena is still lacking. The botulinum neurotoxins (BoNTs) are commonly used for many different indications. There will be weakness as long as there is residual toxin in the nerve ending. Toxins are zinc dependent proteases, and supplemental zinc may produce a greater effect. The time from injection to weakness is determined by how long it takes to get sufficient damage of the SNARE proteins to interfere with synaptic release. Toxin in the general circulation has a long half time. The times for washout from the extracellular space and uptake of the toxin are not well established, but are likely measured in minutes. Encouraging the unwanted muscle contractions after injection should be helpful. The uptake is activity and temperature dependent. Toxin that is not taken up will go into the general circulation where it may have a slight systemic effect.
Toxin is distributed mainly by convection and there is likely little diffusion.
More toxin will be taken up if near the endplate. After toxin is injected into a muscle, it resides in the extracellular space and must be taken up into the nerve terminals. While the steps in the action of botulinum neurotoxin (BoNT) are well known, the factors underlying the timing of these steps are not fully understood.
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