Pharmacology and Immunology of Botulinum Neurotoxins

Abstract

The first clinical uses of botulinum toxin type A were in ophthalmology for the treatment of strabismus and blepharospasm. 1,2 These uses established the safe and effective focal relaxation of extraocular and facial muscles that would later form the basis for the management of facial lines with botulinum toxin type A. Over the past decade, the use of botulinum toxin type A in facial aesthetics has grown tremendously, and today such injections are the most popular nonsurgical cosmetic procedures in the United States. 3 Currently only one product, BOTOX Cosmetic (Allergan, Irvine, CA), is approved for cosmetic use (eg, indicated for the temporary improvement in the appearance of moderate to severe glabellar [frown] lines associated with corrugator and/or procerus muscle activity in adult patients aged 65 years or younger) in the United States.The effects of botulinum toxin type A in facial aesthetics and ophthalmology are a result of its inhibition of acetylcholine release at the neuromuscular junction after local injection. 4 Specific features of the botulinum neurotoxin preparation, such as serotype and formulation, also contribute to its clinical profile. This chapter describes the basic features of botulinum neurotoxins and their pharmacology, with a focus on issues relevant for oculofacial and aesthetic plastic surgeons.n Synthesis and Structure of Botulinum Neurotoxins Botulinum neurotoxins are proteins that are produced by several different clostridial bacterial species and are related to tetanus toxin. 5 The neurotoxin proteins are synthesized along with several hemagglutinin and/or nontoxin nonhemagglutinin proteins that together form a protein complex that has been referred to as progenitor toxin. 6 The associated 25

The evolution of botulinum neurotoxin type A for cosmetic applications

“…Each toxin unit is non-covalently bound to non-toxin proteins (with molecular weights of 300, 500, or 900 kDa) that protect the toxin against degradation (30). Both types A and B target peripheral cholinergic neurons, inhibiting acetylcholine release and causing neuromuscular paralysis (29).…”

Use of botulinum toxin in urology: a literature review

“…Today, the most commonly used subtypes are BoNT-A and Type B. Numerous comparative studies have demonstrated that Type A is more potent and long-acting than Type B (10)(11)(12)(13)(14).…”

Clinical Comparisons of Botulinum Neurotoxin Formulations

“…BoNT serotype A forms the largest possible (900 kD) complex. 8 In all of the complexes, regardless of serotype, the active neurotoxin is approximately the same size (150 kD). 8 All BoNTs act at the presynaptic nerve terminal to inhibit the vesicle-dependent release of acetylcholine and other neurotransmitters from somatic and autonomic nerve terminals (Fig.…”

“…The different sites of action underlie the different mechanisms of action of the serotypes. 8 By inhibiting neurotransmitter release, BoNTs reduce muscle contraction, glandular secretion, or afferent signaling. 9 The resulting functional denervation of target muscle or gland by BoNT is termed "chemodenervation."…”