Botulinum Toxin Type B

Identification

Name
Botulinum Toxin Type B
Accession Number
DB00042  (BTD00070, BIOD00070)
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Other protein based therapies
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.

Protein structure
Db00042
Protein chemical formula
Not Available
Protein average weight
150804.0 Da
Sequences
>Botulinum neurotoxin type B - Clostridium botulinum
MPVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFN
KSSGIFNRDVCEYYDPDYLNTNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLG
DRRVPLEEFNTNIASVTVNKLISNPGEVERKKGIFANLIIFGPGPVLNENETIDIGIQNH
FASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGYFSDPALILMHELIHVLHGLY
GIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIV
DRLNKVLVCISDPNININIYKNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETN
IAENYKIKTRASYFSDSLPPVKIKNLLDNEIYTIEEGFNISDKDMEKEYRGQNKAINKQA
YEEISKEHLAVYKIQMCKSVKAPGICIDVDNEDLFFIADKNSFSDDLSKNERIEYNTQSN
YIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQY
LYSQTFPLDIRDISLTSSFDDALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVND
FVIEANKSNTMDKIADISLIVPYIGLALNVGNETAKGNFENAFEIAGASILLEFIPELLI
PVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLIVAQWLSTVNTQFYTIKEGMY
KALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSV
SYLMKKMIPLAVEKLLDFDNTLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDL
SIYTNDTILIEMFNKYNSEILNNIILNLRYKDNNLIDLSGYGAKVEVYDGVELNDKNQFK
LTSSANSKIRVTQNQNIIFNSVFLDFSVSFWIRIPKYKNDGIQNYIHNEYTIINCMKNNS
GWKISIRGNRIIWTLIDINGKTKSVFFEYNIREDISEYINRWFFVTITNNLNNAKIYING
KLESNTDIKDIREVIANGEIIFKLDGDIDRTQFIWMKYFSIFNTELSQSNIEERYKIQSY
SEYLKDFWGNPLMYNKEYYMFNAGNKNSYIKLKKDSPVGEILTRSKYNQNSKYINYRDLY
IGEKFIIRRKSNSQSINDDIVRKEDYIYLDFFNLNQEWRVYTYKYFKKEEEKLFLAPISD
SDEFYNTIQIKEYDEQPTYSCQLLFKKDEESTDEIGLIGIHRFYESGIVFEEYKDYFCIS
KWYLKEVKRKPYNLKLGCNWQFIPKDEGWTE
Download FASTA Format
Synonyms
  • Botulinum neurotoxin type B precursor
  • BTX-B
  • RimabotulinumtoxinB
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MyoblocInjection, solution10000 [USP'U]/2mLIntramuscularSolstice Neurosciences2000-12-08Not applicableUs
MyoblocSolution5000 unitIntramuscularSolstice NeurosciencesNot applicableNot applicableCanada
MyoblocInjection, solution5000 [USP'U]/1mLIntramuscularSolstice Neurosciences2000-12-08Not applicableUs
MyoblocInjection, solution2500 [USP'U]/0.5mLIntramuscularSolstice Neurosciences2000-12-08Not applicableUs
International/Other Brands
Neurobloc (Solstice Neurosciences)
Categories
UNII
0Y70779M1F
CAS number
93384-44-2

Pharmacology

Indication

For the treatment of patients with cervical dystonia to reduce the severity of abnormal head position and neck pain associated with cervical dystonia.

Associated Conditions
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.

Mechanism of action

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.

TargetActionsOrganism
AVesicle-associated membrane protein 2
binder
Human
AVesicle-associated membrane protein 1
binder
Human
ASynaptotagmin-2Not AvailableHuman
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.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

One unit of Botulinum Toxin Type B corresponds to the calculated median lethal intraperitoneal dose (LD50) in mice.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe risk or severity of adverse effects can be increased when (2-benzhydryloxyethyl)diethyl-methylammonium iodide is combined with Botulinum Toxin Type B.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Botulinum Toxin Type B is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Botulinum Toxin Type B.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Botulinum Toxin Type B.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Botulinum Toxin Type B.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe risk or severity of adverse effects can be increased when 5-(2-methylpiperazine-1-sulfonyl)isoquinoline is combined with Botulinum Toxin Type B.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Botulinum Toxin Type B is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Botulinum Toxin Type B.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline is combined with Botulinum Toxin Type B.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Botulinum Toxin Type B.
Food Interactions
Not Available

References

General References
  1. Montecucco C, Molgo J: Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol. 2005 Jun;5(3):274-9. [PubMed:15907915]
  2. 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. 1999 Oct 22;53(7):1431-8. [PubMed:10534247]
  3. Shukla HD, Sharma SK: Clostridium botulinum: a bug with beauty and weapon. Crit Rev Microbiol. 2005;31(1):11-8. [PubMed:15839401]
  4. Eisenach JH, Atkinson JL, Fealey RD: Hyperhidrosis: evolving therapies for a well-established phenomenon. Mayo Clin Proc. 2005 May;80(5):657-66. [PubMed:15887434]
  5. Schurch B, Corcos J: Botulinum toxin injections for paediatric incontinence. Curr Opin Urol. 2005 Jul;15(4):264-7. [PubMed:15928517]
External Links
UniProt
P10844
Genbank
M81186
KEGG Drug
D02735
PubChem Substance
46504750
ChEMBL
CHEMBL1201569
Therapeutic Targets Database
DAP001272
PharmGKB
PA164747061
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Botulinum_toxin
ATC Codes
M03AX01 — Botulinum toxin
AHFS Codes
  • 92:92.00 — Other Miscellaneous Therapeutic Agents
FDA label
Download (1.18 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHyperhidrosis1
1RecruitingTreatmentCervical Pain / Low Back Pain (LBP)1
1, 2CompletedTreatmentCerebral Palsy (CP)1
2Active Not RecruitingTreatmentSystemic Sclerosis Patients With Digital Ulcers1
2CompletedTreatmentCervical Dystonia / Spasmodic Torticollis1
2CompletedTreatmentDrooling1
2CompletedTreatmentSpasmodic Torticollis1
2RecruitingTreatmentHyperhidrosis1
2, 3CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS) / Sialorrhea1
3CompletedTreatmentSialorrhea2
4CompletedTreatmentBrain Injury / Spasticity Secondary to Either a Disorder or Trauma / Spinal Cord Injuries (SCI) / Strokes / Tumors1
4CompletedTreatmentCervical Dystonia1
4CompletedTreatmentFocal Dystonias1
4TerminatedTreatmentLow Back Pain (LBP)1
Not AvailableActive Not RecruitingTreatmentHidradenitis Suppurativa (HS)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Solstice Neurosciences
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular10000 [USP'U]/2mL
Injection, solutionIntramuscular2500 [USP'U]/0.5mL
Injection, solutionIntramuscular5000 [USP'U]/1mL
SolutionIntramuscular5000 unit
Prices
Unit descriptionCostUnit
Myobloc 10000 unit/2ml Solution 2ml Vial1245.5USD vial
Myobloc 2500 unit/0.5 ml vial299.4USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Syntaxin-1 binding
Specific Function
Involved in the targeting and/or fusion of transport vesicles to their target membrane. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1.
Gene Name
VAMP2
Uniprot ID
P63027
Uniprot Name
Vesicle-associated membrane protein 2
Molecular Weight
12662.585 Da
References
  1. Liu W, Montana V, Chapman ER, Mohideen U, Parpura V: Botulinum toxin type B micromechanosensor. Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13621-5. Epub 2003 Oct 22. [PubMed:14573702]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Snare binding
Specific Function
Involved in the targeting and/or fusion of transport vesicles to their target membrane.
Gene Name
VAMP1
Uniprot ID
P23763
Uniprot Name
Vesicle-associated membrane protein 1
Molecular Weight
12901.815 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
General Function
Syntaxin binding
Specific Function
Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicle...
Gene Name
SYT2
Uniprot ID
Q8N9I0
Uniprot Name
Synaptotagmin-2
Molecular Weight
46871.95 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Poulain B, Lonchamp E, Jover E, Popoff MR, Molgo J: [Mechanisms of action of botulinum toxins and neurotoxins]. Ann Dermatol Venereol. 2009 May;136 Suppl 4:S73-6. doi: 10.1016/S0151-9638(09)74531-4. [PubMed:19576489]

Drug created on June 13, 2005 07:24 / Updated on September 20, 2018 23:57