Amphetamines, methylphenidate and excessive sleepiness

History Amphetamine is a synthetic sympathomimetic stimulant that bears close structural similarity to the endogenous compounds, epinephrine and norepinephrine (Figure 35.1a–c). The word “amphetamine” is an acronym foralpha-methylphenethylamine. It was first synthesized in 1887, by the Romanian chemist Lazăr Edeleanu, who named the compound phenylisopropylamine. Amphetamine is the basic structural element in a number of centrally active compounds that are collectively known as “amphetamines” and that range in activity from central stimulants to hallucinogens. Amphetamines that are approved for use for the treatment of narcolepsy include dextroamphetamine (the more active d-isomer of racemic amphetamine), racemic amphetamine, and various combinations of d-amphetamine and racemic amphetamine. The American Academy of Sleep Medicine's Practice Parameters for the Treatment of Narcolepsy and Other Hypersomnias of Central Origin indicate that methamphetamine (Figure 35.1d) is also an effective treatment. However, use of methamphetamine for this purpose is off-label. Brand names of the drugs in the United States that contain, or metabolize into, amphetamine include Adderall, Vyvanse, and Dexedrine. The brand name for methamphetamine is Desoxyn. Although initially synthesized in 1887, no clinical use was found for amphetamine until 1927, when the chemist and psychopharmacologist Gordon Alles, while working with the allergist George Piness, re-synthesized it in search of an artificial replacement for ephedrine. The bronchodilator and hypertensive properties of amphetamines, as well as their ability to reverse barbiturate anesthesia, were recognized shortly thereafter, and amphetamines were marketed as nasal inhalers to relieve nasal congestion.