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Amphetamine is the trivial name and acronym for racemic β-phenylisopropylamine or α-methylphenylethylamine. Numerous substitutions of the phenylethylamine structure are possible, resulting in different amphetamine like compounds. Commonly, these compounds are referred to as amphetamines or amphetamine analogs, although phenylethylamine is the more precise term. For the purposes of this chapter, the term amphetamines refers to amphetamine analogs, and amphetamine specifically refers to β-phenylisopropylamine.

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Since the initial marketing of amphetamines, continued abuse and misuse have been substantial.18,103,184 Over the years amphetamines have been advocated by the medical communities for the treatment of depression, obesity, enuresis, postencephalitic parkinsonism, coma, ADHD, and even alcoholism.103,139

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Currently, there are very few medical indications for amphetamines, which include narcolepsy, attention deficit hyperactivity disorder, and short-term weight reduction.124 The prescriptive amphetamines include methylphenidate, pemoline, phentermine, phendimetrazine, amphetamine, dextroamphetamine, and methamphetamine. Due to their structural differences, some amphetamines can technically be marketed as nonamphetamine products. There continues to be a resurgence of amphetamine abuse, particularly with methamphetamine and methylenedioxymethamphetamine (MDMA).49,101,208,210,268,275

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Edeleano first synthesized amphetamine (racemic β-phenylisopropylamine) in 1887.103 However, it was not rediscovered until the 1920s, when there was significant concern about the supply of ephedrine for asthma therapy. In the search for the synthesis for ephedrine, Alles from UCLA rediscovered dextroamphetamine, and Ogata from Japan discovered methamphetamine (d-phenylisopropylmethylamine hydrochloride).103 Amphetamine was marketed as Benzedrine inhaler, a nasal decongestant, by Smith, Kline, and French in 1932.18 Amphetamine tablets were available in 1935 for the treatment of narcolepsy, and were advocated as anorexiants in 1938. The stimulant and euphoric effects of amphetamines were widely recognized, resulting in diverse forms of abuse and misuse. Amphetamine abuse was reported as early as 1936.139 Benzedrine inhalers, each containing 250 mg of amphetamine, were widely abused, leading to a ban by the FDA in 1959. Propylhexedrine found in Benzedrex inhalers, a less-potent amphetamine like xenobiotic marketed in 1949, supplanted Benzedrine inhalers.7 Propylhexedrine was also significantly misused.7

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Both amphetamine and methamphetamine were supplied as stimulants for soldiers and prisoners of war in World War II.18,185 Widespread methamphetamine abuse in Japan persisted for more than a decade after the war. From 1950 to the 1970s, there were sporadic periods of widespread amphetamine use and abuse in the United States. In the 1960s, various amphetamine derivatives such as methylenedioxyamphetamine (MDA) and para-methoxyamphetamine (PMA) were popularized as hallucinogens.47 Until 1971, only a small proportion of the amphetamines produced by pharmaceutical companies was used for legitimate medical problems.103,187 The Controlled Substance Act of 1970 placed amphetamines in Schedule II to prevent the diversion of pharmaceutical amphetamines for nonmedicinal uses.54 Amphetamine abuse subsequently declined in the 1970s.39,149,183,187

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In the 1980s, the so-called designer amphetamines (Table 75–1), mostly methylenedioxy derivatives of amphetamine and methamphetamine, came into vogue, ...

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