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Botulinum toxin: Mode of action and serotypes
Abstract
Botulinum toxin comprises a light and a heavy chain protein molecule. The heavy chain attaches the molecule to the nerve membrane, allowing the light chain to reach the site of action at the protein complex in the nerve ending. The toxin inhibits the release of acetylcholine at the neuromuscular junction and can inhibit contraction for 12 weeks before new nerve endings bud and restore function. The autonomic cholinergic receptors are also blocked, for up to 12 months. Central action can result from anterograde and retrograde axonal transport with secondary reduction of elements of the basal ganglia. Antinociceptive effects are due to blockades of pain and inflammatory mediator release. The different serotypes act on different elements of the vesicle-associated membrane protein/synaptosomal-associated protein-25/syntaxin protein complex. The development of antibodies to the protein complex is reported in 2% with serotype A (BOTOX) as opposed to 20% to 40% with serotype B (Myobloc).
Keywords
BOTOX, Dysport, neurotoxin, antinociceptive, serotype
A working knowledge of the pharmacology of botulinum toxin (BTX) is essential to understand the contraindications and complications of treatment with it.
Botulinum neurotoxins are metalloprotease polypeptides, comprising a protein molecule (150 Kd), which can be cleaved enzymatically into a heavy (H) (100 Kd) and a light (L) (50 Kd) chain ( Fig. 2.1 ). These chains are normally held together by a disulphide bond, which is heat labile. Disruption of this bond inactivates the neurotoxin. This explains why BTX must be stored at the correct temperature and reconstituted carefully, preserving the integrity of the two-chained molecule. Prior to reconstitution, characteristics of Incobotulinum toxin A (Xeomin) reflect the lack of a complexing protein with the neurotoxin, allowing lpng term stability and reduced immunogenicity.
Diagram of botulinum toxin molecule showing heavy and light chains. (From Aoki R. The development of Botox—its history and pharmacology. Pain Digest . 1998;8:337–341. With permission from Springer-Verlag.)
BTX induces paralysis by blocking the release of acetylcholine at the skeletal alpha motor neurone neuromuscular junction, thereby inhibiting the transmission of nerve impulses across the synaptic junction to the motor end plate.
User Tip
Always consider possible central, as well as obvious peripheral, changes to the injected muscle following treatment (neuromodulation).
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