A working knowledge of the pharmacology of botulinum toxin is essential to understand the contraindications and complications of treatment with it. Botulinum neurotoxins are polypeptides. Botulinum toxin comprises a protein molecule (150kd) which can be cleaved into a heavy (H)(100kd) and a light (L)(50kd) chain. These chains are normally held together by a disulphide bond,which is heat labile. Disruption of this bond inactivates the neurotoxin. This explains why botulinum toxin must be stored at the correct temperature and reconstituted carefully, preserving the integrity of the twochained molecule (see below).
Botulinum toxin induces paralysis by blocking the release of acetylcholine at the skeletal neuromuscular junction, thereby inhibiting the transmission of nerve impulses across the synaptic junction to the motor end plate. There are seven serotypes of botulinum toxin, five of which are effective at the human neuromuscular junction (BTX A, B, E, F and G). The different serotypes act by cleaving different proteins at the presynaptic vesicle.
Three types of botulinum toxin are currently available commercially: Botox and Dysport (both botulinum toxin Type A); and NeuroBloc (botulinum toxin Type B). Allergan in Westport, Ireland produces Botox. Dysport is produced by Ipsen Pharmaceuticals,UK, and NeuroBloc is produced by Elan, Ireland. NeuroBloc is licensed for use in cervical dystonia under the name ofMyobloc in USA.
Voluntary muscle contraction is a response to stimulation by action potentials passing along a nerve to the muscle. Once these action potentials reach a synapse at the neuromuscular junction, they stimulate an influx of calcium into the cytoplasm of the nerve ending. This increase in calcium concentration allows acetylcholine to fuse with the membrane, using a protein complex, before crossing the synapse and fusing with nicotinic receptors on the muscle fiber. The protein complex consists of three types of protein:VAMP (synaptobrevin), SNAP-25 (synaptosomal associated protein), and syntaxin.
Acetylcholine depends on a protein complex for its release from the nerve ending into the synapse. Botulinum toxin, using a specific enzyme in the light (L) chain, interacts with one component of the protein complex of the nerve terminal, thereby inhibiting the discharge of the acetylcholine. The protein attacked is specific to the different serotypes of botulinum toxin. BTX-A blocks SNAP-25,while BTX-B blocks VAMP. This explains why the development of antibodies to BTX-A (Botox or Dysport) does not preclude a good clinical result from BTX-B (NeuroBloc).
Both the heavy (H) and light (L) chains of the botulinum toxin molecule are needed to block the release of acetylcholine.The H-chain attaches the botulinum toxin to the nerve membrane, allowing the L-chain to be transported to its site of action – the protein complex.The L-chain enzyme then cleaves the protein specific to the particular neurotoxin. Neuromuscular transmission ceases and the target muscle atrophies reversibly.
If botulinum toxin is not handled correctly before injection, the fragile bond which holds the L and H chains together may split, preventing the H-chain from being able to guide the L-chain to the correct protein inside the terminal, and rendering the molecule ineffective.
Botulinum toxin acts only on the neuromuscular cholinergic receptors unless given in very high doses,when autonomic effects may be possible. Botulinum toxin acts by blocking the release of acetylcholine from the pre-synaptic terminal of the neuromuscular junction.
Our website is not responsible for the information contained by this article. Articleinput.com is a free articles resource thus practically any visitor can submit an article. However if you notice any copyrighted material, please contact us and we will remove the article(s) in discussion right away.
Note: This article was sent to us by: Kyle G. Allen at 06152010
1. What you should consider when choosig your cosmetic surgeon
All articles are property of their respective authors. Please read our Privacy Policy!
© 2009 ArticleInput.com.