The idea that a poison could be used as a medicine was first stated by Claude Bernard in 1885. However, botulinum toxin,
“the most poisonous substance known” according to the head of the Infant Botulism Prevention Program at the California Department of Health Services, was only clinically tested in 1980, one hundred years after the statement. The clinicals were for the
treatment of the involuntary mandatory eye muscle disorder and proved to be successful. As a result, in 1989 the Food and Drug Association (FDA) licensed Botox, the first bacterial toxin to be used medicinally, as a treatment for diseases caused by involuntary muscle contractions. Further trials indicated that Botox was a good treatment for tremors caused by Parkinson’s disease, excessive sweating (hyperhidrosis), cervical dystonia and studies are still debating whether Botox is useful for treating migraines. Like many other scientific discoveries the use of Botox as an anti-wrinkle was actually an accident. Jean Carruthers, a Canadian doctor, was treating a patient for the wandering eye when the patient noticed that the wrinkles from her forehead had disappeared. Carruthers was quick to realize the cosmetic use of this drug and in 2002 Botox gained FDA approval as an anti-wrinkle for people 65 years of age or younger. Botulinum toxin injections continue to be one of the most popular chemical procedures for reviving the face.
The toxin exists in seven structurally similar forms or serotypes known as A, B, C1, D, E, F and G. Although structurally similar, these forms have different immunological properties. This is due to the difference in their complex sizes, substrate cleavage sites, duration of action and target affinity. Type A, the safest form of the toxin, is the form used in Botox and is a 900 kDa complex made of a proteolytically cleaved neurotoxin, hemagglutinin molecules (HA) and a non-toxic non-hemagglutinin protein (NTNH). The neurotoxin is cleaved so that it is in its active form. This is done using bacterial enzymes. The use of the HA and the NTNH, however, is still to be discovered. Despite the serotypes being so different the toxin works using the same mechanism for all.
Botulinum toxin is a Zinc dependent neurotoxin that enters the cholinergic neurons and binds to the nerve endings. By interfering with the cellular pathway and cleaving SNARE proteins, the proteins that guide vesicles to their correct location and help them fuse their membranes with the target’s membrane; it prevents the neurotransmitter acetylcholine from being released. Type A of the toxin cleaves the protein SNAP-25. Once the cleaving occurs and there is no acetylcholine present, no signal is sent to the cholinergic
receptors. These receptors are responsible for the transmission of information from the senses to the brain and any return messages. Cholinergic receptors are utilized when there is some muscle activity required. For instance a person smelling a stench would send a signal to the brain and the brain would send one back making the person back away from the smell. With Botox preventing the acetylcholine from being released, the nerve signals from the brain to the muscle that cause muscle impulse are blocked. This causes the muscle to relax and become weak. In a sense the toxin paralyzes the muscle. Barbara Karp of the National Institute of Neurological Disorders and Stroke explains that the toxin, “blocks extra
contractions but leave enough strength for normal use.” Likewise if Botox is injected into the forehead tissues it causes them to weaken. If the tissue is weak it can’t contract therefore making it impossible for a person to form the undesired face expression. As the tissues that gathered together to cause the wrinkles are no longer in use, the wrinkles soon disappear. It takes about a week to see the effects of Botox. The change generally lasts for 3 to 4 months and after this period the toxin needs to be injected once aagain. However, with repeated Botox treatment the muscle may become thinner which would result in the Botox having a prolonged effect.