93384-43-1

Botulinum toxin purified neurotoxin complex (Botox) is a purified form of botulinum toxin type A, produced from a culture of Clostridium botulinum. Injection of botulinum toxin into muscle induces paralysis by inhibiting the release of acetylcholine from motor neurons, thereby blocking neuromuscular conduction. It is approved for the treatment of blepharospasm, strabismus, and excessive sweating. Botox is also approved for use in dermatology to induce paralysis of the muscles of facial expression to reverse deep wrinkles. The effect of an individual treatment usually becomes apparent within 3 days and lasts approximately 3 months. The effect may persist for a longer period after a series of treatments because the muscles atrophy. The major adverse effect is temporary loss of function of a muscle required for normal social functioning, as may occur after inadvertent injection of muscles required for smiling or raising the upper eyelids.

Botulism is most commonly caused by ingestion of a neurotoxin produced by Clostridium botulinum in improperly canned food. Poisoning may also occur after wound contamination with the organism. Infant botulism may occur when spores of the organism germinate and manufacture the toxin in the intestinal tract of infants. Botulinum toxin works by inhibiting ACh release at all cholinergic synapses.
Botulinum toxins are classified into seven antigenically distinct types, A through G. Each consists of a polypeptide chain of about 150,000 daltons. All but one is nicked by trypsin-type enzymes to yield a light and heavy chain linked by a disulfide bridge.One end of the heavy chain mediates binding to the nerve terminal, and the other initiates internalization of the toxin. The light chain produces the intracellular inhibition of ACh release. This involves a Zn-dependent endopeptidase action to cleave synaptic target proteins that control vesicle docking and fusion with the prejunctional membrane.

Botulinum toxin is used clinically in the treatment of blepharospasm, writer’s cramp, spasticities of various origins, and rigidity due to extrapyramidal disorders. It is also used to treat gustatory sweating and cosmetically to decrease facial wrinkles. Botulinum toxin A (Botox, Oculinum) injected intramuscularly produces functional denervation that lasts about 3 months. Clinical benefit is seen within 1 to 3 days.Adverse effects range from diplopia and irritation with blepharospasm to muscle weakness with dystonias.

Botulinum toxin is the most toxic substance known. One gram of crystalline toxin adequately dispersed can kill a population of a million people, so its use in bioterrorism is a possibility. The toxin can be introduced through inhalation or ingestion but not through dermal exposure. The threat of mass inhalation poisoning is limited by the ability or inability to aerosolize the toxin for widespread dispersion. Contaminating the water or food supply is also a possibility, although the toxin is degraded by standard water treatment and by heating of foods to 85°C (185°F) for 5 minutes. Prior immunization with toxoid vaccine is advisable for personnel at risk, but prophylactic administration of trivalent equine antitoxin is not recommended.

This bacterial toxin and neurotoxin (FW = 149.3 kDa; CAS 93384-43-1; abbreviated as BTX or BoNT) from Gram-positive Clostridium botulinum are ADP-ribosyltransferases and proteases that give rise to the clinical manifestations of botulism. Classification: BTX consists of seven antigenically and serologically distinct neurotoxins (types A, B, C1, C2, C3, D, E, F, and G) that are otherwise functionally and structurally similar. Human botulism is caused mainly by types A, B, E, and (rarely) F. Types C and D cause toxicity only in animals. Each botulinum toxin possesses individual potencies, necessitating special care to avoid medication errors. Recent changes to the established drug names by the FDA were intended to reinforce these differences and prevent medication errors. They include the following: exotoxins, which inhibit the release of catecholamines from the adrenal medulla and block the release of acetylcholine at neuromuscular junctions. The seven distinct types of exotoxin are now labeled A through G, each consisting of two peptide chains linked by a disulfide bond. Chain I of botulinum toxin C2 catalyzes the ADP-ribosylation of G-actin and prevents actin polymerization. Neurotoxic Effects: Following the attachment of the botulinum toxin’s heavy chain to one or more proteins on the exterior surface of axon terminals, the toxin is taken by neurons via endocytosis. The light chain cleaves endocytotic vesicles and enters the cytoplasm, where it proteolytically degrades the SNAP-25 protein, a type of SNARE protein involved in vesicle trafficking. SNAP-25 is essential for vesicle fusion, a step that is required for release of neurotransmitters, particular acetylcholine, from the axon endings Botulinum toxin thereby prevents neurosecretory vesicles from docking/fusing with the nerve synapse plasma membrane and releasing their neurotransmitters. Clinical Applications: Injectable formulations of OnabotulinumtoxinA (INN generic name) are now used to treat blepharospasm or strabismus, to relieve neck pain, resulting from cervical dystonia, and for muscle stiffness in the elbow, wrist, and finger muscles in adult patients with upper limb spasticity. Botox is often employed to prevent chronic migraine and cosmetically to improve the appearance of deep facial lines or furrows between eyebrows and creases in the skin around the eyes. Patients with urinary incontinence and overactive bladder can also benefit from appropriate application. Target (s) : catecholamine release; acetylcholine release; actin polymerization .