Botulinum Toxin in BOTOX® Cosmetic

The BOTOX® Cosmetic website defines botulinum toxin injections as “a prescription medicine that is injected into muscles and used to improve the look of moderate-to-severe frown lines between the eyebrows (glabellar lines) in adults younger than 65 years of age for a short time (temporary)” (BOTOX® Cosmetic, 2010).

In 1949, Burgen’s group discovered that neuromuscular transmission gets blocked when in contact with the Clostridium botulinum toxin. In 1973, Alan B. Scott, MD, of the Smith-Kettlewell Eye Research Institute experimented with the botulinum toxin type A (BTX-A) on monkeys; by 1980, BTX-A was used for the first time in humans. In December 1989, BOTOX® was approved by the FDA and could officially be administered through injections. BOTOX® and BOTOX® Cosmetics then originated and is now manufactured by Allergan Inc. (a global pharmaceutical company that specializes in neuromodulator, eye care, and skin care) in Irvine, California for both therapeutic and cosmetic use (BOTOX® Cosmetic, 2010). According to the American Society of Plastic Surgeons, as of 2007, BOTOX® Cosmetic injections were the most common cosmetic operation and accounted for 4.6 million procedures in the United States.

BOTOX® Cosmetic contains botulinum toxin typeA (active ingredient) as well as human albumin and sodium chloride (inactive ingredients) (BOTOX® Cosmetic, 2010). The active botulinum toxin included in the ingredients has been purified for medical purposes so it will be less likely to cause botulism. In the unpurified form, the toxin interferes with nerve impulses and weakens or paralyzes the nerves that can cause abnormal muscle contractions for a period of time (Simpson, 1981).

Clostridium botulinum is a spore-forming, obligate anaerobe whose natural habitat is the soil. Unique strains of Clostridium baratii and Clostridium butyricum also have the capacity to produce the botulinum toxin (Simpson, 1981). The botulinum toxin is on of the most poisonous substance known. It is colorless, odorless, and tasteless. The lethal dose of botulinum toxin for humans has been estimated from previous primate studies. It is very toxic with an LD₅₀ of 0.005-0.05 µg/kg. A single gram of crystalline toxin would kill more than 1 million people if it were evenly dispersed and inhaled (even though technical factors make this scenario difficult). Due to these factors, it is even believed that botulinum toxin can pose as a major bioweapon threat. It not only has extreme potency and lethality, but it is easy to produce, transport, and misuse (Arnon, 2001).

The potency of the botulinum toxin is enzymatic. The structure consists of a di-chain polypeptide containing a 100-kd “heavy” chain joined to a 50-kd “light” chain by a disulfide bond. Since the light chain is a protease, it cleaves specific sites of the SNARE proteins (i.e. syntaxin, synaptobrevin, or SNAP-25) at the nerve terminus (the SNARE protein cleaved depends on the antigenic type of botulinum toxin present; botulinum types range from A through G). In turn, this prevents the complete assembly of the synaptic fusion complex (does not allow the synaptic membrane vesicles from attaching to the neuronal cell membrane) to release acetylcholine (a chemical compound that acts as a neurotransmitters in the nervous system) (Simpson, 1981). As previously stated, the inhibition of acetylcholine in the nervous system interferes with the normal functioning of nerve impulses, which can cause a weakened and sagging paralysis of the muscles due to the occurrence of botulism (Arnon, 2001).

Even though BOTOX® Cosmetics uses a purified version of the botulinum toxin and has low levels of toxicity, it is still likely to spread to areas of the body away from the injection site and cause major side effects including headaches, double vision, blurred vision, drooping eyelids, flu-like symptoms, allergic reactions, dysphonia, and dysarthria. Some life threatening side effects include problems breathing and swallowing. It also still carries the threat of being inhaled by the patient, which in turn can prove to be dangerous (BOTOX® Cosmetic). However, equine antitoxins (Trivalent Botulinum Antitoxin and Heptavalent Botulinum Antitoxin) have been derived to prevent such dangerous situations from occurring (Arnon, 2001).