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Pharmacology of Botulinum Toxins: From Poison to Remedy

Year 2020, , 71 - 78, 30.08.2020
https://doi.org/10.18678/dtfd.777234

Abstract

Botulinum toxin (BTX) is produced by autolysis of several strains of Clostridium botulinum, a gram-positive, spore-forming, rod-shaped, strictly anaerobic bacterium. However there are also non-clostridial microorganisms that are enable to produce the toxin. As some other beneficial poison, BTX also fits well the quotations by old scientists and philosophers like “Almost every substance can become a poison but only thing is the dose discriminating the difference” (Paracelsus, XVI century) or “Poisons can be employed as a means for the destruction of life or as agents for the treatment of the sick” (Claude Bernard, XIX century) or “Poison is a medicine, medicine is a poison” (Ahi Evran, XIII century). In the 1980's, Alan Scott first published articles on the use of BTX for the treatment of strabismus. The Food and Drug Administration of the USA (FDA) first approved botulinum toxin for the treatment of strabismus (crossed eye) blepharospasm (uncontrollable eye blinking) in 1989 and for glabellar rhytides in 2002, the first cosmetic indication. Since then BTX has been used for a verity of indications not only dermatological but also non-dermatological indications including on-labelled as well as off-labelled uses. In this review you will find the pharmacological profile of botulinum toxins, i.e., mode of action, pharmacokinetics, adverse effects, indications and contrindications, drug interactions, duration and site of action, etc. Furthermore, current commercial products and novel dosage forms as well as new perspective of BTX use will also be discussed.

References

  • Johnson EA, Bradshaw M. Clostridium botulinum and its neurotoxins: A metabolic and cellular perspective. Toxicon. 2001;39(11):1703-22.
  • Pirazzini M, Rossetto O, Eleopra R, Montecucco C. Botulinum neurotoxins: Biology, pharmacology, and toxicology. Pharmacol Rev. 2017;69(2):200-35.
  • Erbguth FJ. Historical notes on botulism, clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Mov Disord. 2004;19(Suppl 8):S2-6.
  • Nawrocki EM, Bradshaw M, Johnson EA. Botulinum neurotoxin-encoding plasmids can be conjugatively transferred to diverse clostridial strains. Sci Rep. 2018;8(1):3100.
  • Lindström M, Korkeala H. Laboratory diagnostics of botulism. Clin Microbiol Rev. 2006;19(2):298-314.
  • Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol. 2010;55(1):8-14.
  • Nepal MR, Jeong TC. Alternative methods for testing botulinum toxin: Current status and future perspectives. Biomol Ther (Seolu). 2020;[Online first]. doi: https://doi.org/10.4062/biomolther.2019.200.
  • Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus. 1980;17(1):21-5.
  • Carruthers JA, Lowe NJ, Menter MA, Gibson J, Nordquist M, Mordaunt J, et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002;46(6):840-9.
  • Fonfria E, Maignel J, Lezmi S, Martin V, Splevins A, Shubber S, et al. The expanding therapeutic utility of botulinum neurotoxins. Toxins (Basel). 2018;10(5):208.
  • Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol Rev. 2000;80(2):717-66.
  • Humeau Y, Doussau F, Grant NJ, Poulain B. How botulinum and tetanus neurotoxins block neurotransmitter release. Biochimie. 2000;82(5):427-46.
  • Pearce LB, First ER, MacCallum RD, Gupta A. Pharmacologic characterization of botulinum toxin for basic science and medicine. Toxicon. 1997;35(9):1373-412.
  • Kim YI, Lømo T, Lupa MT, Thesleff S. Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin. J Physiol. 1984;356(1):587-99.
  • Kumar R, Dhaliwal HP, Kukreja RV, Singh BR. The botulinum toxin as a therapeutic agent: Molecular structure and mechanism of action in motor and sensory systems. Semin Neurol. 2016,36(1):10-9.
  • Nakanishi ST, Cope TC, Rich MM, Carrasco DI, Pinter MJ. Regulation of motoneuron excitability via motor endplate acetylcholine receptor activation. J Neurosci. 2005;25(9):2226-32.
  • Whelchel DD, Brehmer TM, Brooks PM, Darragh N, Coffield JA. Molecular targets of botulinum toxin at the mammalian neuromuscular junction. Mov Disord. 2004;19(Suppl 8):S7-16.
  • Čapek P, Dickerson TJ. Sensing the deadliest toxin: technologies for botulinum neurotoxin detection. Toxins (Basel). 2010;2(1):24-53.
  • Aktories K. Bacterial toxins that target Rho proteins. J Clin Invest. 1997;99(5): 827-9.
  • Poulain B, Lemichez E, Popoff MR. Neuronal selectivity of botulinum neurotoxins. Toxicon. 2020;178:20-32.
  • Zhou Y, Liu Y, Hao Y, Feng Y, Pan L, Liu W, et al. The mechanism of botulinum A on Raynaud syndrome. Drug Des Devel Ther. 2018;12:1905-15.
  • Grando SA, Zachary CB. The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond. Br J Dermatol. 2018;178(5):1011-9.
  • Katzung BG. Autonomic drugs. In: Katzung BG, editor. Basic & clinical pharmacology. 9th ed. New York: McGraw-Hill; 2004. p.76
  • Mauriello Jr JA. Blepharospasm, meige syndrome, and hemifacial spasm: treatment with botulinum toxin. Neurology. 1985;35(10):1499-500.
  • Shorr N, Seiff SR, Kopelman J. The use of botulinum toxin in blepharospasm. Am J Ophthalmol. 1985;99(5):542-6.
  • Jankovic J, Orman J. Botulinum A toxin for cranial-cervical dystonia: a double-blind, placebo-controlled study. Neurology. 1987;37(4):616-23.
  • Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol Neck Surg. 2000;123(6):669-76.
  • Favre-Guilmard C, Auguet M, Chabrier PE. Different antinociceptive effects of botulinum toxin type A in inflammatory and peripheral polyneuropathic rat models. Eur J Pharmacol. 2009;617(1-3):48-53.
  • Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107(1-2):125-33.
  • Bach-Rojecky L, Lacković Z. Central origin of the antinociceptive action of botulinum toxin type A. Pharmacol Biochem Behav. 2009;94(2):234-8.
  • Bach-Rojecky L, Salković-Petrisić M, Lacković Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection. Eur J Pharmacol. 2010;633(1-3):10-4.
  • Love SC, Novak I, Kentish M, Desloovere K, Heinen F, Molenaers G, et al. Botulinum toxin assessment, intervention and after-care for lower limb spasticity in children with cerebral palsy: international consensus statement. Eur J Neurol. 2010;17(Suppl 2):9-37.
  • Do TP, Hvedstrup J, Schytz HW. Botulinum toxin: A review of the mode of action in migraine Acta Neurol Scand. 2018;137(5):442-51.
  • Lin YH, Chiang BJ, Liao CH. Mechanism of action of botulinum toxin A in treatment of functional urological disorders. Toxins (Basel). 2020;12(2):129.
  • Hehr JD, Schoenbrunner AR, Janis JE. The use of botulinum toxin in pain management: Basic science and clinical applications, plastic and reconstructive surgery. 2020;145(3):629e-36e.
  • Yucesoy CA, Ateş F. BTX-A has notable effects contradicting some treatment aims in the rat triceps surae compartment, which are not confined to the muscles injected. J Biomech. 2018;66:78-85.
  • Yucesoy CA, Emre Arıkan Ö, Ateş F. BTX-A administration to the target muscle affects forces of all muscles within an intact compartment and epimuscular myofascial force transmission. J Biomech Eng. 2012;134(11):111002.
  • Zakin E, Simpson D. Evidence on botulinum toxin in selected disorders. Toxicon. 2018;147:134-40.
  • Ferreira JR, Souza RP. Botulinum toxin for vaginismus treatment. Pharmacology. 2012;89(5-6):256-9.
  • Chiu SY, Patel B, Burns MR, Legacy J, Shukla AW, Ramirez-Zamora A, et al. High-dose botulinum toxin therapy: Safety, benefit, and endurance of efficacy. Tremor Other Hyperkinet Mov (NY). 2020;10. doi: http://doi.org/10.5334/tohm.527
  • Klein AW. Contraindications and complications with the use of botulinum toxin. Clin Dermatol. 2004;22(1):66-75.
  • Highlights of prescribing information of BOTOX® Initial U.S. Approval: 1989;1-22.
  • Lueangarun S, Sermsilp C, Tempark T. Topical botulinum toxin type A liposomal cream for primary axillary hyperhidrosis: A double-blind, randomized, split-site, vehicle-controlled study. Dermatol Surg. 2018;44(8):1094-101.
  • Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol. 2014;7(2):31-9.
  • Ravichandran E, Gong Y, Al Saleem FH, Ancharski DM, Joshi SG, Simpson LL. An initial assessment of the systemic pharmacokinetics of botulinum toxin. J Pharmacol Exp Ther. 2006;318(3):1343-51.
  • Mazzocchio R, Caleo M. More than at the neuromuscular synapse: Actions of botulinum neurotoxin A in the central nervous system. Neuroscientist. 2015;21(1):44-61.
  • Priori A, Berardelli A, Mercuri B, Manfredi M. Physiological effects produced by botulinum toxin treatment of upper limb dystonia. Changes in reciprocal inhibition between forearm muscles. Brain. 1995;118(Pt 3):801-7.
  • Valls-Sole J, Tolosa ES, Ribera G. Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. J Neurol Neurosurg Psychiatry. 54(4):310-3.
  • Antonucci F, Di Garbo A, Novelli E, Manno I, Sartucci F, Bozzi Y, et al. Botulinum neurotoxin E (BoNT/E) reduces CA1 neuron loss and granule cell dispersion, with no effects on chronic seizures, in a mouse model of temporal lobe epilepsy. Exp Neurol. 2008;210(2):388-401.
  • Bomba-Warczak E, Vevea JD, Brittain JM, Figueroa-Bernier A, Tepp WH, Johnson EA, et al. Interneuronal transfer and distal action of tetanus toxin and botulinum neurotoxins A and D in central neurons. Cell Rep. 2016;16(7):1974-87.
  • Koizumi H, Goto S, Okita S, Morigaki R, Akaike N, Torii Y, et al. Spinal central effects of peripherally applied botulinum neurotoxin A in comparison between its subtypes A1 and A2. Front Neurol. 2014;5:98.
  • Matak I, Lacković Z. Botulinum toxin A, brain and pain. Prog Neurobiol. 2014;119-120:39-59.
  • Restani L, Novelli E, Bottari D, Leone P, Barone I, Galli-Resta L, et al. Botulinum neurotoxin A impairs neurotransmission following retrograde transynaptic transport. Traffic. 2012;13(8):1083-9.
  • Currà A, Trompetto C, Abbruzzese G, Berardelli A. Central effects of botulinum toxin type A: Evidence and supposition. Mov Disord. 2004;19(Suppl 8):S60-4.
  • Wiegand H, Wellhöner HH. The action of botulinum A neurotoxin on the inhibition by antidromic stimulation of the lumbar monosynaptic reflex. Naunyn Schmiedebergs Arch Pharmacol. 1977;298(3):235-8.
  • Salinas S, Schiavo G, Kremer EJ. A hitchhiker's guide to the nervous system: the complex journey of viruses and toxins. Nat Rev Microbiol. 2010;8(9):645-55.
  • Donald S, Elliott M, Gray B, Hornby F, Lewandowska A, Marlin S, et al. A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo. Pharmacol Res Perspect. 2018;6(6):e00446.
  • Shaari CM, George E, Wu BL, Biller HF, Sanders I. Quantifying the spread of botulinum toxin through muscle fascia. Laryngoscope. 1991;101(9):960-4.
  • Yaraskavitch M, Leonard T, Herzog W. Botox produces functional weakness in non-injected muscles adjacent to the target muscle. J Biomech. 2008;41(4):897-902.
  • Kutschenko A, Weisemann J , Kollewe K, Fiedler T, Alvermann S , Böselt S, et al. Botulinum neurotoxin serotype D - A potential treatment alternative for BoNT/A and B non-responding patients. Clin Neurophysiol. 2019;130(6):1066-73.
  • Lou J, Marks JD. Botulinum neurotoxins (BoNTs)-antibody and vaccine. Toxins (Basel) 2018;10(12):495.

Botulinum Toksinlerinin Farmakolojisi: Zehirden Çareye

Year 2020, , 71 - 78, 30.08.2020
https://doi.org/10.18678/dtfd.777234

Abstract

Botulinum toksini (BTX) Gram (+), sporlu, çubuk şekilli ve mutlak anareobik bir bakteri olan Clostridium botulinum’un parçalanması sonucu üretilir. Ancak bu toksini üretebilen Clostridium-olmayan mikroorganizmalar da bulunmaktadır. Faydalı olabilen bazı toksinler gibi BTX de, eski bilim insanları ya da filozofların “Hemen herşey zehir olabilmektedir, farkı yaratan dozdur” (Paracelsus, XVI yüzyıl) veya “Zehirler yaşamı tahrip etmek veya hastaları tedavi etmek için kullanılabilir” (Claude Bernard, XIX yüzyıl) ya da “Zehir ilaçtır, ilaç zehirdir” (Ahi Evran, XIII yüzyıl) gibi tanımlamalarına çok uymaktadır. 1980’lerde Alan Scott, şaşılık tedavisinde BTX’in kullanımı ile ilgili ilk makaleleri yayımlamıştır. Amerikan Gıda ve İlaç Dairesi (FDA), 1989’da strabismus (şaşılık) and blefarospazm (kontrol edilemeyen göz kırpması) tedavisi için, 2002’de de ilk kozmetik indikasyon olarak kaş-arası dikey kırışıklıklarının tedavisi için ilk kez BTX’i onaylamıştır. O günden beri BTX, sadece dermatolojik değil aynı zamanda dermatolojik-olmayan pek çok indikasyonda, hem onaylı hem de onaysız olarak kullanılmaktadır. Bu derlemede botulinum toksininin etki mekanizmaları, farmakokinetiği, yan etkileri, indikasyon ve kontrindikasyonları, ilaç etkileşmeleri, etki yerleri ve etki süresi vd pek çok açıdan farmakolojik profilini bulacaksınız. Ayrıca mevcut ticari ürünleri ve yeni dozaj formları ve aynı zamanda BTX’in gelecekteki kullanımı konusu da tartışılacaktır.

References

  • Johnson EA, Bradshaw M. Clostridium botulinum and its neurotoxins: A metabolic and cellular perspective. Toxicon. 2001;39(11):1703-22.
  • Pirazzini M, Rossetto O, Eleopra R, Montecucco C. Botulinum neurotoxins: Biology, pharmacology, and toxicology. Pharmacol Rev. 2017;69(2):200-35.
  • Erbguth FJ. Historical notes on botulism, clostridium botulinum, botulinum toxin, and the idea of the therapeutic use of the toxin. Mov Disord. 2004;19(Suppl 8):S2-6.
  • Nawrocki EM, Bradshaw M, Johnson EA. Botulinum neurotoxin-encoding plasmids can be conjugatively transferred to diverse clostridial strains. Sci Rep. 2018;8(1):3100.
  • Lindström M, Korkeala H. Laboratory diagnostics of botulism. Clin Microbiol Rev. 2006;19(2):298-314.
  • Nigam PK, Nigam A. Botulinum toxin. Indian J Dermatol. 2010;55(1):8-14.
  • Nepal MR, Jeong TC. Alternative methods for testing botulinum toxin: Current status and future perspectives. Biomol Ther (Seolu). 2020;[Online first]. doi: https://doi.org/10.4062/biomolther.2019.200.
  • Scott AB. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus. 1980;17(1):21-5.
  • Carruthers JA, Lowe NJ, Menter MA, Gibson J, Nordquist M, Mordaunt J, et al. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002;46(6):840-9.
  • Fonfria E, Maignel J, Lezmi S, Martin V, Splevins A, Shubber S, et al. The expanding therapeutic utility of botulinum neurotoxins. Toxins (Basel). 2018;10(5):208.
  • Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol Rev. 2000;80(2):717-66.
  • Humeau Y, Doussau F, Grant NJ, Poulain B. How botulinum and tetanus neurotoxins block neurotransmitter release. Biochimie. 2000;82(5):427-46.
  • Pearce LB, First ER, MacCallum RD, Gupta A. Pharmacologic characterization of botulinum toxin for basic science and medicine. Toxicon. 1997;35(9):1373-412.
  • Kim YI, Lømo T, Lupa MT, Thesleff S. Miniature end-plate potentials in rat skeletal muscle poisoned with botulinum toxin. J Physiol. 1984;356(1):587-99.
  • Kumar R, Dhaliwal HP, Kukreja RV, Singh BR. The botulinum toxin as a therapeutic agent: Molecular structure and mechanism of action in motor and sensory systems. Semin Neurol. 2016,36(1):10-9.
  • Nakanishi ST, Cope TC, Rich MM, Carrasco DI, Pinter MJ. Regulation of motoneuron excitability via motor endplate acetylcholine receptor activation. J Neurosci. 2005;25(9):2226-32.
  • Whelchel DD, Brehmer TM, Brooks PM, Darragh N, Coffield JA. Molecular targets of botulinum toxin at the mammalian neuromuscular junction. Mov Disord. 2004;19(Suppl 8):S7-16.
  • Čapek P, Dickerson TJ. Sensing the deadliest toxin: technologies for botulinum neurotoxin detection. Toxins (Basel). 2010;2(1):24-53.
  • Aktories K. Bacterial toxins that target Rho proteins. J Clin Invest. 1997;99(5): 827-9.
  • Poulain B, Lemichez E, Popoff MR. Neuronal selectivity of botulinum neurotoxins. Toxicon. 2020;178:20-32.
  • Zhou Y, Liu Y, Hao Y, Feng Y, Pan L, Liu W, et al. The mechanism of botulinum A on Raynaud syndrome. Drug Des Devel Ther. 2018;12:1905-15.
  • Grando SA, Zachary CB. The non-neuronal and nonmuscular effects of botulinum toxin: an opportunity for a deadly molecule to treat disease in the skin and beyond. Br J Dermatol. 2018;178(5):1011-9.
  • Katzung BG. Autonomic drugs. In: Katzung BG, editor. Basic & clinical pharmacology. 9th ed. New York: McGraw-Hill; 2004. p.76
  • Mauriello Jr JA. Blepharospasm, meige syndrome, and hemifacial spasm: treatment with botulinum toxin. Neurology. 1985;35(10):1499-500.
  • Shorr N, Seiff SR, Kopelman J. The use of botulinum toxin in blepharospasm. Am J Ophthalmol. 1985;99(5):542-6.
  • Jankovic J, Orman J. Botulinum A toxin for cranial-cervical dystonia: a double-blind, placebo-controlled study. Neurology. 1987;37(4):616-23.
  • Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM. Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label study. Otolaryngol Neck Surg. 2000;123(6):669-76.
  • Favre-Guilmard C, Auguet M, Chabrier PE. Different antinociceptive effects of botulinum toxin type A in inflammatory and peripheral polyneuropathic rat models. Eur J Pharmacol. 2009;617(1-3):48-53.
  • Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004;107(1-2):125-33.
  • Bach-Rojecky L, Lacković Z. Central origin of the antinociceptive action of botulinum toxin type A. Pharmacol Biochem Behav. 2009;94(2):234-8.
  • Bach-Rojecky L, Salković-Petrisić M, Lacković Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection. Eur J Pharmacol. 2010;633(1-3):10-4.
  • Love SC, Novak I, Kentish M, Desloovere K, Heinen F, Molenaers G, et al. Botulinum toxin assessment, intervention and after-care for lower limb spasticity in children with cerebral palsy: international consensus statement. Eur J Neurol. 2010;17(Suppl 2):9-37.
  • Do TP, Hvedstrup J, Schytz HW. Botulinum toxin: A review of the mode of action in migraine Acta Neurol Scand. 2018;137(5):442-51.
  • Lin YH, Chiang BJ, Liao CH. Mechanism of action of botulinum toxin A in treatment of functional urological disorders. Toxins (Basel). 2020;12(2):129.
  • Hehr JD, Schoenbrunner AR, Janis JE. The use of botulinum toxin in pain management: Basic science and clinical applications, plastic and reconstructive surgery. 2020;145(3):629e-36e.
  • Yucesoy CA, Ateş F. BTX-A has notable effects contradicting some treatment aims in the rat triceps surae compartment, which are not confined to the muscles injected. J Biomech. 2018;66:78-85.
  • Yucesoy CA, Emre Arıkan Ö, Ateş F. BTX-A administration to the target muscle affects forces of all muscles within an intact compartment and epimuscular myofascial force transmission. J Biomech Eng. 2012;134(11):111002.
  • Zakin E, Simpson D. Evidence on botulinum toxin in selected disorders. Toxicon. 2018;147:134-40.
  • Ferreira JR, Souza RP. Botulinum toxin for vaginismus treatment. Pharmacology. 2012;89(5-6):256-9.
  • Chiu SY, Patel B, Burns MR, Legacy J, Shukla AW, Ramirez-Zamora A, et al. High-dose botulinum toxin therapy: Safety, benefit, and endurance of efficacy. Tremor Other Hyperkinet Mov (NY). 2020;10. doi: http://doi.org/10.5334/tohm.527
  • Klein AW. Contraindications and complications with the use of botulinum toxin. Clin Dermatol. 2004;22(1):66-75.
  • Highlights of prescribing information of BOTOX® Initial U.S. Approval: 1989;1-22.
  • Lueangarun S, Sermsilp C, Tempark T. Topical botulinum toxin type A liposomal cream for primary axillary hyperhidrosis: A double-blind, randomized, split-site, vehicle-controlled study. Dermatol Surg. 2018;44(8):1094-101.
  • Walker TJ, Dayan SH. Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol. 2014;7(2):31-9.
  • Ravichandran E, Gong Y, Al Saleem FH, Ancharski DM, Joshi SG, Simpson LL. An initial assessment of the systemic pharmacokinetics of botulinum toxin. J Pharmacol Exp Ther. 2006;318(3):1343-51.
  • Mazzocchio R, Caleo M. More than at the neuromuscular synapse: Actions of botulinum neurotoxin A in the central nervous system. Neuroscientist. 2015;21(1):44-61.
  • Priori A, Berardelli A, Mercuri B, Manfredi M. Physiological effects produced by botulinum toxin treatment of upper limb dystonia. Changes in reciprocal inhibition between forearm muscles. Brain. 1995;118(Pt 3):801-7.
  • Valls-Sole J, Tolosa ES, Ribera G. Neurophysiological observations on the effects of botulinum toxin treatment in patients with dystonic blepharospasm. J Neurol Neurosurg Psychiatry. 54(4):310-3.
  • Antonucci F, Di Garbo A, Novelli E, Manno I, Sartucci F, Bozzi Y, et al. Botulinum neurotoxin E (BoNT/E) reduces CA1 neuron loss and granule cell dispersion, with no effects on chronic seizures, in a mouse model of temporal lobe epilepsy. Exp Neurol. 2008;210(2):388-401.
  • Bomba-Warczak E, Vevea JD, Brittain JM, Figueroa-Bernier A, Tepp WH, Johnson EA, et al. Interneuronal transfer and distal action of tetanus toxin and botulinum neurotoxins A and D in central neurons. Cell Rep. 2016;16(7):1974-87.
  • Koizumi H, Goto S, Okita S, Morigaki R, Akaike N, Torii Y, et al. Spinal central effects of peripherally applied botulinum neurotoxin A in comparison between its subtypes A1 and A2. Front Neurol. 2014;5:98.
  • Matak I, Lacković Z. Botulinum toxin A, brain and pain. Prog Neurobiol. 2014;119-120:39-59.
  • Restani L, Novelli E, Bottari D, Leone P, Barone I, Galli-Resta L, et al. Botulinum neurotoxin A impairs neurotransmission following retrograde transynaptic transport. Traffic. 2012;13(8):1083-9.
  • Currà A, Trompetto C, Abbruzzese G, Berardelli A. Central effects of botulinum toxin type A: Evidence and supposition. Mov Disord. 2004;19(Suppl 8):S60-4.
  • Wiegand H, Wellhöner HH. The action of botulinum A neurotoxin on the inhibition by antidromic stimulation of the lumbar monosynaptic reflex. Naunyn Schmiedebergs Arch Pharmacol. 1977;298(3):235-8.
  • Salinas S, Schiavo G, Kremer EJ. A hitchhiker's guide to the nervous system: the complex journey of viruses and toxins. Nat Rev Microbiol. 2010;8(9):645-55.
  • Donald S, Elliott M, Gray B, Hornby F, Lewandowska A, Marlin S, et al. A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo. Pharmacol Res Perspect. 2018;6(6):e00446.
  • Shaari CM, George E, Wu BL, Biller HF, Sanders I. Quantifying the spread of botulinum toxin through muscle fascia. Laryngoscope. 1991;101(9):960-4.
  • Yaraskavitch M, Leonard T, Herzog W. Botox produces functional weakness in non-injected muscles adjacent to the target muscle. J Biomech. 2008;41(4):897-902.
  • Kutschenko A, Weisemann J , Kollewe K, Fiedler T, Alvermann S , Böselt S, et al. Botulinum neurotoxin serotype D - A potential treatment alternative for BoNT/A and B non-responding patients. Clin Neurophysiol. 2019;130(6):1066-73.
  • Lou J, Marks JD. Botulinum neurotoxins (BoNTs)-antibody and vaccine. Toxins (Basel) 2018;10(12):495.
There are 61 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Invited Review
Authors

Kansu Büyükafşar 0000-0003-4117-6013

Publication Date August 30, 2020
Submission Date June 10, 2020
Published in Issue Year 2020

Cite

APA Büyükafşar, K. (2020). Pharmacology of Botulinum Toxins: From Poison to Remedy. Duzce Medical Journal, 22(2), 71-78. https://doi.org/10.18678/dtfd.777234
AMA Büyükafşar K. Pharmacology of Botulinum Toxins: From Poison to Remedy. Duzce Med J. August 2020;22(2):71-78. doi:10.18678/dtfd.777234
Chicago Büyükafşar, Kansu. “Pharmacology of Botulinum Toxins: From Poison to Remedy”. Duzce Medical Journal 22, no. 2 (August 2020): 71-78. https://doi.org/10.18678/dtfd.777234.
EndNote Büyükafşar K (August 1, 2020) Pharmacology of Botulinum Toxins: From Poison to Remedy. Duzce Medical Journal 22 2 71–78.
IEEE K. Büyükafşar, “Pharmacology of Botulinum Toxins: From Poison to Remedy”, Duzce Med J, vol. 22, no. 2, pp. 71–78, 2020, doi: 10.18678/dtfd.777234.
ISNAD Büyükafşar, Kansu. “Pharmacology of Botulinum Toxins: From Poison to Remedy”. Duzce Medical Journal 22/2 (August 2020), 71-78. https://doi.org/10.18678/dtfd.777234.
JAMA Büyükafşar K. Pharmacology of Botulinum Toxins: From Poison to Remedy. Duzce Med J. 2020;22:71–78.
MLA Büyükafşar, Kansu. “Pharmacology of Botulinum Toxins: From Poison to Remedy”. Duzce Medical Journal, vol. 22, no. 2, 2020, pp. 71-78, doi:10.18678/dtfd.777234.
Vancouver Büyükafşar K. Pharmacology of Botulinum Toxins: From Poison to Remedy. Duzce Med J. 2020;22(2):71-8.