Botulinum toxin type A

Targets (2)

Identification

Accession Number

DB00083

Description

Purified botulinum toxin from Clostridium botulinum, purified from culture via dialysis and acid precipitation.

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Other protein based therapies

Protein Structure

Protein Chemical Formula: C₆₇₆₀H₁₀₄₄₇N₁₇₄₃O₂₀₁₀S₃₂
Protein Average Weight: 149322.7 Da

Sequences

>Botulinum Toxin Type A Sequence
MPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLN
PPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGG
STIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGY
GSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPN
RVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKA
KSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKV
LNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFT
GLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEE
ITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNG
KKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEA
AMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSG
AVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAK
VNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKA
MININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDK
VNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINI
GSKVNFDPIDKNQIQLFNLESSKIEVILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNN
EYTIINCMENNSGWKVSLNYGEIIWTLQDTQEIKQRVVFKYSQMINISDYINRWIFVTIT
NNRLNNSKIYINGRLIDQKPISNLGNIHASNNIMFKLDGCRDTHRYIWIKYFNLFDKELN
EKEIKDLYDNQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPR
GSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQA
GVEKILSALEIPDVGNLSQVVVMKSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAK
LVASNWYNRQIERSSRTLGCSWEFIPVDDGWGERPL

Download FASTA Format

Synonyms

AbobotulinumtoxinA
Botulinum A neurotoxin
Botulinum toxin A
Botulinum toxin type A
BTX-A
Evabotulinumtoxina
IncobotulinumtoxinA
OnabotulinumtoxinA
Prabotulinumtoxin A
Toxina botulínica A
Toxine botulinique A

External IDs

AGN 191622
ANT-1207
ANT-1401
ANT-1403
NT 201

Pharmacology

Indication

For the treatment of cervical dystonia in adults to decrease the severity of abnormal head position and neck pain associated with cervical dystonia. Also for the treatment of severe primary axillary hyperhidrosis that is inadequately managed with topical agents and for the treatment of strabismus and blepharospasm associated with dystonia, including benign essential blepharospasm or VII nerve disorders in patients 12 years of age and above. Also used cosmetically to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines) as well as for the treatment of excessive underarm sweating.

Associated Conditions

Associated Therapies

Contraindications & Blackbox Warnings

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Pharmacodynamics

A 150 kDa neurotoxic protein produced from fermentation of Hall strain Clostridium botulinum type A grown in a medium containing casein hydrolysate, glucose and yeast extract. It is purified from the culture solution by dialysis and a series of acid precipitations to a complex consisting of the neurotoxin, and several accessory proteins. Botulinum Toxin Type A is not expected to be present in the peripheral blood at measurable levels following IM or intradermal injection at the recommended doses. The recommended quantities of neurotoxin administered at each treatment session are not expected to result in systemic, overt distant clinical effects, i.e. muscle weakness, in patients without other neuromuscular dysfunction. However, sub-clinical systemic effects have been shown by single-fiber electromyography after IM doses of botulinum toxins appropriate to produce clinically observable local muscle weakness.

Mechanism of action

Botulinum Toxin Type A blocks neuromuscular transmission by binding to acceptor sites on motor or sympathetic nerve terminals, entering the nerve terminals, and inhibiting the release of acetylcholine. This inhibition occurs as the neurotoxin cleaves SNAP-25, a protein integral to the successful docking and release of acetylcholine from vesicles situated within nerve endings.

Target	Actions	Organism
ASynaptosomal-associated protein 25	inhibitor	Humans
URho-related GTP-binding protein RhoB	Not Available	Humans

Absorption

The chemical complexity of Botulinum Toxin Type A combined with its extreme potency limits the opportunity to study its pharmacokinetic profile in humans. Therefore, no human pharmacokinetic studies have been performed. Botulinum Toxin Type A is injected directly into the target organ, a skeletal muscle. Thus, bioavailability of the intravenous or oral route is not of clinical relevance.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects

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Toxicity

Based on toxicological studies, it has been estimated that the human LD50 by injection is approximately 2800 Units, equivalent to 28 individual vials of BOTOX (Botulinum Toxin Type A) Purified Neurotoxin Complex (100 Units) for a 70 kg adult. When injected intramuscularly, Botulinum Toxin Type A has been shown to be teratogenic or to have embryocidal effects in some animal species.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
Unlock Additional Data
Acetazolamide	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Acetazolamide.
Acetophenazine	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Acetophenazine.
Aclidinium	The risk or severity of adverse effects can be increased when Aclidinium is combined with Botulinum toxin type A.
Agomelatine	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Agomelatine.
Alfentanil	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Alfentanil.
Alimemazine	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Alimemazine.
Almotriptan	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Almotriptan.
Alosetron	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Alosetron.
Alprazolam	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Alprazolam.
Alverine	The risk or severity of adverse effects can be increased when Botulinum toxin type A is combined with Alverine.

Additional Data Available

Extended Description

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Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

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A severity rating for each drug interaction, from minor to major.

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Evidence Level

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A rating for the strength of the evidence supporting each drug interaction.

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Action

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An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

Products

Purchasing individual compounds or compound libraries for your research?

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Unlock Additional Data
Botox	Injection, powder, lyophilized, for solution	100 [USP'U]/1	Intradermal; Intramuscular	Allergan, Inc.	1989-12-15	Not applicable
Botox	Injection, powder, lyophilized, for solution	200 [USP'U]/1	Intradermal; Intramuscular	Allergan, Inc.	2010-01-11	Not applicable
Botox	Powder, for solution	100 unit	Intramuscular	Allergan	1992-12-31	Not applicable
BOTOX Cosmetic	Powder, for solution	100 unit	Intramuscular	Allergan	2001-05-07	Not applicable
BOTOX Cosmetic	Injection, powder, lyophilized, for solution	100 [USP'U]/1	Intramuscular	Allergan, Inc.	2008-05-20	Not applicable
BOTOX Cosmetic	Injection, powder, lyophilized, for solution	50 [USP'U]/1	Intramuscular	Allergan, Inc.	2008-07-15	Not applicable
Dysport	Injection, powder, lyophilized, for solution	300 [USP'U]/1	Intramuscular	Medicis Pharmaceutical Corporation	2009-05-25	2015-03-31
Dysport	Injection, powder, lyophilized, for solution	300 U/1	Intramuscular	Galderma Laboratories, L.P.	2009-11-02	Not applicable
Dysport	Injection, powder, lyophilized, for solution	300 U/1	Intramuscular	Ipsen Biopharmaceuticals, Inc.	2009-11-02	Not applicable
Dysport	Injection, powder, lyophilized, for solution	500 U/1	Intramuscular	Ipsen Biopharmaceuticals, Inc.	2009-11-02	Not applicable

Additional Data Available

Application Number

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A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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Product Code

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A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Chemical Identifiers

UNII: E211KPY694
CAS number: 93384-43-1

References

General References

Montecucco C, Molgo J: Botulinal neurotoxins: revival of an old killer. Curr Opin Pharmacol. 2005 Jun;5(3):274-9. [PubMed:15907915]
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]
Shukla HD, Sharma SK: Clostridium botulinum: a bug with beauty and weapon. Crit Rev Microbiol. 2005;31(1):11-8. [PubMed:15839401]
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]
Schurch B, Corcos J: Botulinum toxin injections for paediatric incontinence. Curr Opin Urol. 2005 Jul;15(4):264-7. [PubMed:15928517]

External Links

UniProt: P10845
Genbank: X52066
KEGG Drug: D00783
KEGG Compound: C07946
PubChem Substance: 46505347
RxNav: 1000104
Therapeutic Targets Database: DAP001298
PharmGKB: PA164754825
RxList: RxList Drug Page
Wikipedia: Botulinum_toxin

AHFS Codes

92:92.00 — Other Miscellaneous Therapeutic Agents

FDA label

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Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Facial Rhytides, Skin Folds, Loss of Volume and Skin Quality	1
4	Active Not Recruiting	Treatment	Glabellar Frown Lines	1
4	Active Not Recruiting	Treatment	Mixed Urinary Incontinence / Stress Urinary Incontinence (SUI) / Urgency Incontinence	1
4	Active Not Recruiting	Treatment	Painful Intercourse / Pelvic Floor Dysfunctions / Pelvic Pain	1
4	Active Not Recruiting	Treatment	Spinal Cord Injuries (SCI) / Urinary Bladder, Overactive	1
4	Completed	Not Available	Healthy Subjects, Only With Wrinkles on Forehead	1
4	Completed	Basic Science	Healthy Volunteers	1
4	Completed	Other	Forehead Rhytides / Forehead Wrinkles	1
4	Completed	Other	Glabellar Frown Lines	1
4	Completed	Prevention	Autonomic Dysreflexia	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Allergan Inc.
Tercica Inc.

Dosage Forms

Form	Route	Strength
Injection, powder, for solution	Parenteral	100 U
Injection, powder, for solution	Parenteral	200 U
Injection, powder, lyophilized, for solution	Intradermal; Intramuscular	100 [USP'U]/1
Injection, powder, lyophilized, for solution	Intradermal; Intramuscular	200 [USP'U]/1
Powder, for solution	Intramuscular	100 unit
Injection	Intramuscular	100 U
Injection, powder, for solution	Intradermal; Intramuscular	200 U
Injection, powder, for solution		100 iu
Injection, powder, for solution		300 iu
Injection, powder, for solution		500 iu
Injection, powder, for solution	Intramuscular; Subcutaneous	300 U
Injection, powder, for solution	Intramuscular; Subcutaneous	500 UI
Injection, powder, lyophilized, for solution	Intramuscular	300 U/1
Injection, powder, lyophilized, for solution	Intramuscular	300 [USP'U]/1
Injection, powder, lyophilized, for solution	Intramuscular	500 U/1
Injection, powder, lyophilized, for solution	Intramuscular; Subcutaneous	300 U
Injection, solution	Intramuscular	500 U
Injection, powder, lyophilized, for solution	Intramuscular; Subcutaneous	500 U
Injection, powder, for solution		200 iu
Injection, powder, for solution		50 iu
Powder	Intramuscular	100 [USP'U]/1
Injection, powder, lyophilized, for solution	Intramuscular	200 IU
Injection, powder, for solution	Intramuscular	100 U
Injection, powder, lyophilized, for solution	Intramuscular; Subcutaneous	50 U
Injection, powder, for solution	Parenteral	50 U
Injection, powder, lyophilized, for solution	Intramuscular	100 [USP'U]/1
Injection, powder, lyophilized, for solution	Intramuscular	200 [USP'U]/1
Injection, powder, lyophilized, for solution	Intramuscular	50 [USP'U]/1
Powder, for solution	Intramuscular	50 unit
Powder, for solution	Intramuscular
Injection, powder, lyophilized, for solution	Intramuscular	100 U
Injection, powder, lyophilized, for solution	Intramuscular	50 U

Prices

Unit description	Cost	Unit
Botox 200 unit vial	1260.0USD	vial
Dysport 500 unit vial	852.0USD	vial
Botox 100 unit	655.2USD	vial
Botox 100 unit vial	630.0USD	vial
Botox cosmetic 100 unit vial	630.0USD	vial
Botox cosmetic 50 unit vial	346.8USD	vial
Botox (100 - 200 unit/Vial)	3.74USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)
Unlock Additional Data
CA2280565	No	2005-11-15	2019-08-20
CA2310845	No	2001-05-15	2014-06-07

Additional Data Available

Filed On

Available for Purchase

The date on which a patent was filed with the relevant government.

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Properties

State

Solid

Experimental Properties

Property	Value	Source
water solubility	Soluble	Not Available
hydrophobicity	-0.368	Not Available
isoelectric point	6.06	Not Available

Targets

Details1. Synaptosomal-associated protein 25

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Syntaxin-1 binding
Specific Function: t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesi...
Gene Name: SNAP25
Uniprot ID: P60880
Uniprot Name: Synaptosomal-associated protein 25
Molecular Weight: 23314.905 Da

References

Zhou JY, Wang ZF, Ren XM, Tang MZ, Shi YL: Antagonism of botulinum toxin type A-induced cleavage of SNAP-25 in rat cerebral synaptosome by toosendanin. FEBS Lett. 2003 Dec 4;555(2):375-9. [PubMed:14644446]
Flynn TC: Myobloc. Dermatol Clin. 2004 Apr;22(2):207-11, vii. [PubMed:15222581]
Okada M, Yoshida S, Zhu G, Kaneko S: [Methodological consideration in studying the exocytosis mechanisms using microdialysis]. Nihon Shinkei Seishin Yakurigaku Zasshi. 2004 Aug;24(4):165-70. [PubMed:15484814]
Frassoni C, Inverardi F, Coco S, Ortino B, Grumelli C, Pozzi D, Verderio C, Matteoli M: Analysis of SNAP-25 immunoreactivity in hippocampal inhibitory neurons during development in culture and in situ. Neuroscience. 2005;131(4):813-23. [PubMed:15749336]
Straughan D: Progress in applying the Three Rs to the potency testing of Botulinum toxin type A. Altern Lab Anim. 2006 Jun;34(3):305-13. [PubMed:16831062]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details2. Rho-related GTP-binding protein RhoB

Kind: Protein
Organism: Humans
Pharmacological action: Unknown

General Function: Gtpase activity
Specific Function: Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative r...
Gene Name: RHOB
Uniprot ID: P62745
Uniprot Name: Rho-related GTP-binding protein RhoB
Molecular Weight: 22123.185 Da

References

Ishida H, Zhang X, Erickson K, Ray P: Botulinum toxin type A targets RhoB to inhibit lysophosphatidic acid-stimulated actin reorganization and acetylcholine release in nerve growth factor-treated PC12 cells. J Pharmacol Exp Ther. 2004 Sep;310(3):881-9. Epub 2004 May 12. [PubMed:15140914]