The drive to compete and win is as old as humankind. Throughout history, athletes have sought foods and potions to enhance physical performance. Stimulants were one of the first groups of substances which clearly gave an advantageous effect and could help the athlete go through the pain-barrier.
The Roman gladiators of Circus Maximus used stimulants mixed with alcohol to overcome fatigue and injuries. Scandinavian warriors (the Berserkers) ate hallucinogenic mushrooms to prepare for battle. The first competitive athletes charged for stimulant abuse were swimmers in Amsterdam in the 1860s. In the late 19th century European cyclists were using substances such as caffeine and ether-soaked sugar cubes and strychnine to reduce pain and delay fatigue. The first reported drug-related death in sports (Arthur Linton in 1896) is believed to be because of the stimulant strychnine.
Shortly after the Second World War, amphetamine became very popular resulting in several lethal cases. One of the most well-known doping victims in that period was Tom Simpson who died in 1967 on Mont Ventoux from a combination of exhaustion, alcohol, and amphetamines. In the same year the International Olympic Committee (IOC) created a Medical Commission that initiated the introduction of anti-doping regulations. The first official list of prohibited substances which they published contained exclusively stimulants.
Advances in organic chemistry in the 1950s and 1960s yielded a wide variety of stimulant compounds. In particular, the ability of stimulants to be used as appetite suppressors, useful for the treatment of obesity, made this group attractive to the pharmaceutical industry. The challenging task was to minimize the side effects and to maximize the appetite suppression. Unfortunately, the addictive character and the danger of paranoia attacks, typical for stimulant (ab)use, could not be abolished and many stimulants are no longer therapeutically available. Nevertheless these old compounds remain present on the black market.
Despite the danger to health of most stimulants, some compounds of this class successfully found their way to therapeutic use. An important group are the compounds which increase alertness without the addictive potential of traditional stimulants. They also have minimal effect on sleep structure and do not result in rebound hypersomnolence. Currently, there are two stimulants in this class: modafinil and adrafinil. Other stimulants still frequently used therapeutically are pseudoephedrine (PEPH), used for the treatment of nasal congestion, and methylphenidate (also known as ritaline), used to treat attentiondefici-thyperactivity-disorder (ADHD). Because the prohibited list published by the World Anti-Doping Agency (WADA) mentions the names of 64 stimulants, only a selection is discussed here. Structures of these are presented in Fig. 1; for all substances the trivial names, as commonly used by the anti-doping community, will be used throughout this paper.
As already mentioned above, the list of prohibited substances published by WADA explicitly mentions 64 stimulants. Stimulants are the second biggest class after the anabolic steroids. Except that caffeine and PEPH were removed in January 2004 and PEPH was reintroduced in January 2010, no major modifications have been made to this class since WADA took over the fight against doping from the IOC in 2000. The stimulants are divided in two categories: nonspecified and specified. For non-specified stimulants (37 compounds) no reduction of the basic sanction can be obtained, i.e. 2 years ineligibility for a first violation. If an athlete or other person can establish how a specified stimulant entered his or her body or came into his or her possession and that such stimulant was not intended to enhance the athlete’s sport performance, the period of ineligibility can be adjusted (= reduced). These specified stimulants are mainly compounds which might be used therapeutically, for example ephedrines and methylphenidate. Alongside the specified and non-specified stimulants this class also contains substances which assigned doping laboratories should monitor and report their findings to WADA. These compounds include, bupropion, caffeine, phenylephrine, phenylpropanolamine, pipradol, and synephrine. Based upon the outcome of the monitoring programme these compounds could be included or withdrawn from the list.
- Deventer & K. Roels & F. T. Delbeke & P. Van Eenoo. Anal Bioanal Chem (2011) 401:421–432