1. Drugbank ID: DB00042 Protein average weight : 150804.0000
Botulinum Toxin Type B
Drugbank ID: DB00042
Protein average weight :

2. Description
Neurotoxin produced by fermentation of clostridium botulinum type B. The protein exists in noncovalent association with hemagglutinin and nonhemagglutinin proteins as a neurotoxin complex. The neurotoxin complex is recovered from the fermentation process and purified through a series of precipitation and chromatography steps.
Indication
For the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia.
Pharmacodynamics
Botulinum Toxin Type B inhibits acetylcholine release at the neuromuscular junction via a three stage process: 1) Heavy Chain mediated neurospecific binding of the toxin, 2) internalization of the toxin by receptor-mediated endocytosis, and 3) ATP and pH dependent translocation of the Light Chain to the neuronal cytosol where it acts as a zinc-dependent endoprotease cleaving polypeptides essential for neurotransmitter release.

3. Mechanism Of Action Toxicity Absorption Categories Affected Organism
Botulinum Toxin Type B binds to and cleaves the synaptic Vesicle Associated Membrane Protein (VAMP, also known as synaptobrevin) which is a component of the protein complex responsible for docking and fusion of the synaptic vesicle to the presynaptic membrane, a necessary step to neurotransmitter release.
Toxicity
One unit of Botulinum Toxin Type B corresponds to the calculated median lethal intraperitoneal dose (LD50) in mice.
Absorption
Though pharmacokinetic or ADME studies were not performed, Botulinum Toxin Type B is not expected to be present in the peripheral blood at measurable levels following IM injection at the recommended doses.
Categories
Antidystonic Agents
Affected Organism
Humans and other mammals
Targets
Vesicle-associated membrane protein 2,Vesicle-associated membrane protein 1,Synaptotagmin-2

4. Sequence Botulinum neurotoxin type B - Clostridium botulinum
MPVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFNKSSGIFNRDVCEYYDPDYLNTNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLGDRRVPLEEFNTNIASVTVNKLISNPGEVERKKGIFANLIIFGPGPVLNENETIDIGIQNHFASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGYFSDPALILMHELIHVLHGLYGIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIVDRLNKVLVCISDPNININIYKNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETNIAENYKIKTRASYFSDSLPPVKIKNLLDNEIYTIEEGFNISDKDMEKEYRGQNKAINKQAYEEISKEHLAVYKIQMCKSVKAPGICIDVDNEDLFFIADKNSFSDDLSKNERIEYNTQSNYIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQYLYSQTFPLDIRDISLTSSFDDALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVNDFVIEANKSNTMDKIADISLIVPYIGLALNVGNETAKGNFENAFEIAGASILLEFIPELLIPVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLIVAQWLSTVNTQFYTIKEGMYKALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSVSYLMKKMIPLAVEKLLDFDNTLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDLSIYTNDTILIEMFNKYNSEILNNIILNLRYKDNNLIDLSGYGAKVEVYDGVELNDKNQFKLTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKNDGIQNYIHNEYTIINCMKNNSGWKISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVTITNNLNNAKIYINGKLESNTDIKDIREVIANGEIIFKLDGDIDRTQFIWMKYFSIFNTELSQSNIEERYKIQSYSEYLKDFWGNPLMYNKEYYMFNAGNKNSYIKLKKDSPVGEILTRSKYNQNSKYINYRDLYIGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRVYTYKYFKKEEEKLFLAPISDSDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYESGIVFEEYKDYFCISKWYLKEVKRKPYNLKLGCNWQFIPKDEGWTE

5. Brands :Myobloc Company : Solstice Neurosciences Description : MYOBLOC ® (rimabotulinumtoxinB) injection is a sterile liquid formulation of a purified neurotoxin that acts at the neuromuscular junction to produce flaccid paralysis. The neurotoxin is produced by fermentation of the bacterium Clostridium botulinum type B (Bean strain) and exists in noncovalent association with hemagglutinin and nonhemagglutinin proteins as a neurotoxin complex. The neurotoxin complex is recovered from the fermentation process and purified through a series of precipitation and chromatography steps. Used For/Prescribed for : It is used for reducing the severity of abnormal head position and neck pain associated with a certain neck problem (cervical dystonia) Formulation : It is supplied in 3.5-mL glass vials. Each single-use vial of formulated MYOBLOC contains 5,000 Units of botulinum toxin type B per milliliter in 0.05% human serum albumin, 0.01 M sodium succinate, and 0.1 M sodium chloride at approximately pH 5.6.

6. Form : clear and colorless to light-yellow sterile injectable solution Route of administration : injection Dosage : The recommended initial dose of MYOBLOC (botulinum toxin type b) for patients with a prior history of tolerating botulinum toxin injections is 2,500 to 5,000 Units divided among affected muscles. Patients without a prior history of tolerating botulinum toxin injections should receive a lower initial dose. Subsequent dosing should be optimized according to the patient's individual response. Contraindication : MYOBLOC (botulinum toxin type b) is contraindicated in patients with a known hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation. MYOBLOC (botulinum toxin type b) is contraindicated for use in patients with infection at the proposed injection site

7. Side effects : most COMMON side effects persist or become bothersome: Anxiety; back pain; dizziness; drowsiness; dry eyes; dry mouth; flu-like symptoms; headache; increased cough; indigestion; nausea; neck pain; pain, redness, swelling, or tenderness at the injection site; runny nose; sensitivity to light; sweating; upset stomach; weakness of the muscles at or near the injection site. Seek medical attention right away if any of these SEVERE side effects occur: Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); bleeding at the injection site; chest pain; difficulty swallowing or breathing; double or blurred vision, or other vision changes; drooping eyelid; fever, chills, or persistent sore throat; irregular heartbeat; loss of bladder control; loss of strength; paralysis; pneumonia; seizures; severe or persistent muscle weakness or dizziness; shortness or breath; speech changes or problems; swelling of the hands or feet; vaginal irritation, odor, or discharge; wheezing. Drug Interaction : A total of 362 drugs (2538 brand and generic names) are known to interact with Myobloc (botulinum toxin type b). 22 major drug interactions (53 brand and generic names) 340 moderate drug interactions (2485 brand and generic names)

8. Brands : Neurobloc Company : Solstice Neurosciences Description : Neurobloc (new-roh-blok) is a medicine which is used in muscle spasm of the neck. Neurobloc contains botulinum toxin type b. Used For/Prescribed for : NeuroBloc is indicated for the treatment of cervical dystonia (torticollis) in adults. It means Neurobloc is used to treat muscle spasms of the neck. Formulation : Medicines contain active ingredients. They may also contain other, additional ingredients that help ensure the stability, safety and effectiveness of the medicine. Some may be used to prolong the life of the medicine. Neurobloc contains: botulinum toxin type b disodium succinate human serum albumin hydrochloric acid for pH adjustment sodium chloride water for injections Form : Clear and colourless to light yellow solution Route of administration : Intramuscular injection

9. Dosage : The initial dose is 10,000 U and should be divided between the two to four most affected muscles. Data from clinical studies suggest that efficacy is dose dependent, but these trials, because they were not powered for a comparison, do not show a significant difference between 5000 U and 10,000 U. Therefore an initial dose of 5000 U may also be considered, but a dose of 10,000 U may increase the likelihood of clinical benefit. Injections should be repeated as required to mainta in good function and minimise pain. In long term clinical studies, the average dosing frequency was appr oximately every 12 weeks, however this may vary between subjects and a proportion of patients maintained a significant improvement relative to baseline for 16 weeks or longer. The dosing frequency should therefore be adapted based on the clinical assessment /response of an individual patient. Contraindication : Hypersensitivity and Individuals with known neuromuscular diseases (e.g. amyotrophic lateral sclerosis or peripheral neuropathy) or known neuromuscula r junctional disorders (e.g. myasthenia gravis or Lambert-Eaton syndrome) must not be given NeuroBloc Side effects : The most commonly reported adverse reactions associated with NeuroBloc treatment were dry mouth, dysphagia, dyspepsia, and injection site pain. Drug Interaction : The effect of administering different botulinum neurotoxin serotypes concurrently is unknown. However, in clinical studies, NeuroBloc was administered 16 weeks after the injection of Botulinum Toxin Type A. Co-administration of NeuroBloc and aminoglycos ides or agents interfering with neuromuscular transmission (e.g. curare-like compounds) should be considered with caution.

10. General References
# Montecucco C, Molgo J: Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol Jun;5(3): "Pubmed":
# Brin MF, Lew MF, Adler CH, Comella CL, Factor SA, Jankovic J, O'Brien C, Murray JJ, Wallace JD, Willmer-Hulme A, Koller M: Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia. Neurology Oct 22;53(7): "Pubmed":
# Shukla HD, Sharma SK: Clostridium botulinum: a bug with beauty and weapon. Crit Rev Microbiol. 2005;31(1):11-8. "Pubmed":
# Eisenach JH, Atkinson JL, Fealey RD: Hyperhidrosis: evolving therapies for a well-established phenomenon. Mayo Clin Proc May;80(5): "Pubmed":
# Schurch B, Corcos J: Botulinum toxin injections for paediatric incontinence. Curr Opin Urol Jul;15(4): "Pubmed":

11. Refrence http://www.drugs.com/cdi/myobloc.html