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REVIEW ARTICLES
Handling Botulinum Toxins: An Updated Literature Review
A
DA
R. T
RINDADE
D
E
A
LMEIDA
, MD, L
ETICIA
C
ARDOSO
S
ECCO
, MD,
AND
A
LASTAIR
C
ARRUTHERS
, MD
y
BACKGROUND Botulinum toxin (BoNT) has been in use since the late 1970s, and over the last 20 years,
its use has been extended to new indications in various areas of medicine. During these years of clinical
use, some of the initial ideas have changed, and others have remained stable along with increasing
experience with and knowledge about BoNTs.
OBJECTIVE To review the literature and prescribing information on all of the available products and to
update the concept of handling toxins (preparations, reconstitution, storage, sterility, and dilution).
METHODS A review (not Cochrane type analysis) of the medical literature based on relevant databases
(MEDLINE, PubMed, Cochrane Library, specialist textbooks, and manufacturer information) was
performed.
CONCLUSIONS Many of the precautions around BoNT use, often recommended by the manufacturers,
are described in the clinical literature as too restrictive. The literature suggests that toxins may be
sturdier and more-resistant to degradation than previously understood.
Dr. Ada R. Trindade de Almeida
has been a consultant to Allergan, Inc. and participated in clinical trials for Allergan and Galderma.
Dr. Alastair Carruthers is a consultant to Allergan, Inc. and Merz GmbH and has been paid to do research
for both companies
.
Background
B
otulinum toxin (BoNT) has been in use since the
late 1970s in ophthalmology,
1
and over the
last 20 years, its use has been extended to new
indications in various areas of medicine, in particular
dermatology. It is an effective treatment for strabis-
mus, hemifacial spasm, blepharospasm, cervical
dystonia, spasmodic dysphonia, hyperhidrosis, and
facial rejuvenation.
2
Clostridium botulinum
, a Gram-positive anaerobic
bacterium, produces seven antigenically different
neurotoxins, but only serotypes A and B are
commercially available.
3
Serotype A (BoNTA)
appears to be the most potent subtype.
4
BoNTA is naturally produced as a complex of a
core neurotoxin protein, along with several hemag-
glutinin and nontoxin nonhemagglutinin
proteins.
3,5
The associated proteins serve to
stabilize and protect the neurotoxin molecule from
degradation.
6,7
Under physiologic conditions, the core 150-kDa
protein dissociates from the toxin complex, binds to
synaptic vesicle protein 2 using the heavy chain
component, and enters the neuronal cell by
internalization.
8
Once in the cytosolic surface
membrane, BoNTA binds to and cleaves the 25-kDa
synaptosomal-associated protein (SNAP25), whereas
BoNTB binds to and cleaves the vesicle associated
membrane protein, a component of the soluble
N-ethylmaleimide-sensitive factor attachment
protein receptor family
9
involved in exocytic release
of the neurotransmitters.
10
&
2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.
ISSN: 1076-0512 Dermatol Surg ;37:1553–1565 DOI: 10.1111/j.1524-4725.2011.02087.x
Clı´nica Dermatolo´ gica do Hospital do Servidor Pu´ blico Municipal de Sa˜o Paulo, Sa˜o Paulo, Brazil;
y
Division of
Dermatology, University of British Columbia, Vancouver, British Columbia, Canada.
Reprinted by permission of Dermatol Surg. 2011; 37(11):1553-1565.