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Biologic
RCSB PDB 3BTA

OnabotulinumtoxinA

Botox
Mechanism of action
Acetylcholine release (SNAP-25-cleaving neurotoxin)
In plain language
Works by cutting a protein that nerve endings need to release their chemical signal, temporarily stopping a nerve from telling a muscle to contract or a gland to activate.
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How it works
OnabotulinumtoxinA is a two-chain polypeptide neurotoxin produced by Clostridium botulinum, consisting of a heavy chain and a light chain joined by a single disulfide bond. The heavy chain binds on presynaptic cholinergic nerve terminals and mediates internalization of the toxin. Once inside the cell, the light chain — a zinc-dependent endopeptidase — cleaves SNAP-25, a protein required for docking and fusion of acetylcholine-containing synaptic vesicles with the presynaptic membrane. This blocks stimulus-evoked acetylcholine release at the neuromuscular junction and, depending on injection site, at autonomic cholinergic nerve terminals such as sweat glands. The result is temporary, localized chemical denervation; effect typically resolves over roughly three months as new nerve terminal sprouts restore transmission.
Therapeutic applications
Per FDA-approved labeling, BOTOX (onabotulinumtoxinA) is indicated for prophylaxis of headaches in adult patients with chronic migraine; treatment of spasticity in patients 2 years of age and older; treatment of cervical dystonia in adults; treatment of severe axillary hyperhidrosis; treatment of overactive bladder and neurogenic detrusor overactivity; treatment of blepharospasm associated with dystonia in patients 12 and older; and treatment of strabismus in patients 12 and older. Under a separate BOTOX Cosmetic label, onabotulinumtoxinA is also indicated in adults for temporary improvement in the appearance of glabellar lines, lateral canthal lines, forehead lines, and platysma bands.
Class
Bacterial neurotoxin
Therapeutic area
Neurology
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