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| Primary information |
|---|
| ID | 10419 |
| Therapeutic ID | Th1070 |
| Protein Name | Botulinum Toxin Type A |
| Sequence | >Th1070_Botulinum_Toxin_Type_A
MPFVNKQFNYKDPVNGVDIAYIKIPNVGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVRGIITSKTKSLDKGYNKALNDLCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTFTEYIKNIINTSILNLRYESNHLIDLSRYASKINIGSKVNFDPIDKNQIQLFNLESSKIEVILKNAIVYNSMYENFSTSFWIRIPKYFNSISLNNEYTIINCMENNSGWKVSLNYGEIIWTLQDTQEIKQRVVFKYSQMINISDYINRWIFVTITNNRLNNSKIYINGRLIDQKPISNLGNIHASNNIMFKLDGCRDTHRYIWIKYFNLFDKELNEKEIKDLYDNQSNSGILKDFWGDYLQYDKPYYMLNLYDPNKYVDVNNVGIRGYMYLKGPRGSVMTTNIYLNSSLYRGTKFIIKKYASGNKDNIVRNNDRVYINVVVKNKEYRLATNASQAGVEKILSALEIPDVGNLSQVVVMKSKNDQGITNKCKMNLQDNNGNDIGFIGFHQFNNIAKLVASNWYNRQIERSSRTLGCSWEFIPVDDGWGERPL
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| Molecular Weight | 900000 |
| Chemical Formula | C6760H10447N1743O2010S32 |
| Isoelectric Point | 5.6 |
| Hydrophobicity | -0.368 |
| Melting point | 85.5-86.5 |
| Half-life | 230 to 260 min in a pharmacokinetic study of rats and mice |
| Description | Purified botulinum toxin from Clostridium botulinum, purified from culture via dialysis and acid precipitation. |
| Indication/Disease | 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. |
| 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. |
| 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. |
| Metabolism | NA |
| 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. |
| NA |
| Clearance | NA |
| Categories | Acetylcholine Release Inhibitors, Agents that produce neuromuscular block (indirect), Amino Acids, Peptides, and Proteins, Bacterial Proteins, Bacterial Toxins, Biological Factors, Botulinum Toxins, Botulinum Toxins, Type A, Central Nervous System Depressants, Cholinergic Agents, Endopeptidases, Enzymes, Enzymes and Coenzymes, Ganglion Blockers, Hydrolases, Membrane Transport Modulators, Metalloendopeptidases, Metalloproteases, Muscle Relaxants, Muscle Relaxants, Peripherally Acting Agents, Musculo-Skeletal System, Neuromuscular Agents, Neuromuscular Blocking Agents, Neurotoxins, Neurotransmitter Agents, Noxae, Other Miscellaneous Therapeutic Agents, Peptide Hydrolases, Peripheral Nervous System Agents, Proteins, Toxic Actions, Toxins, Biological |
| Patents Number | CA2280565 |
| Date of Issue | 15-Nov-2005 |
| Date of Expiry | 20-Aug-2019 |
| Drug Interaction | NA |
| Target | Synaptosomal-associated protein 25,Rho-related GTP-binding protein RhoB |
| Brand Name | BOTOX |
| Company | Allergan |
| Brand Description | Allergan |
| Prescribed For | Prescribed in cases such as Bladder Dysfunction, Chronic Migraine, Upper Limb Spasticity, Cervical Dystonia, Primary Axillary Hyperhidrosis, Blepharospasm and Strabismus |
| Chemical Name | NA |
| Formulation | Each vial of BOTOX contains either 50 Units of Clostridium botulinum type A neurotoxin complex, 0.25 mg of Albumin Human, and 0.45 mg of sodium chloride; 100 Units of Clostridium botulinum type A neurotoxin complex, 0.5 mg of Albumin Human, and 0.9 mg of sodium chloride; or 200 Units of Clostridium botulinum type A neurotoxin complex, 1 mg of Albumin Human, and 1.8 mg of sodium chloride in a sterile, vacuum-dried form without a preservative. |
| Physical Appearance | BOTOX (onabotulinum toxin A) For Injection is a sterile, vacuum-dried purified botulinum toxin type A, produced from fermentation of Hall strainClostridium botulinum type A |
| Route of Administration | IntramuSubcutaneousular, intradetrusor and intrade |
| Recommended Dosage | Do not exceed a total dose of 360 Units administered in a 3 month interval. |
| Contraindication | Known Hypersensitivity to Botulinum Toxin, Infection at the Injection Site, Urinary Tract Infection or Urinary Retention. |
| Side Effects | Spread of Toxin Effects, Hypersensitivity, Dysphagia and Breathing Difficulties in Treatment of Cervical Dystonia, Bronchitis and Upper Respiratory Tract Infections in Patients Treated for Spasticity, Urinary Retention in Patients Treated for Bladder Dysfunction. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |