Dextroamphetamine

Dexedrine; Dextrostat

Article: Dextroamphetamine


Dextroamphetamine
Systematic (IUPAC) name
1-phenylpropan-2-amine
Identifiers
CAS number	300-62-9
ATC code	N06BA01
PubChem	5826
DrugBank	APRD00480
Chemical data
Formula	C₉H₁₃N
Mol. weight	135.206 g/mol
Pharmacokinetic data
Bioavailability	~25%
Metabolism	Hepatic
Half life	10-28 hours
Excretion	Renal: ~45%
Therapeutic considerations
Pregnancy cat.	C: (USA) B3: (AUS)
Legal status	Prescription only DEA Schedule II (USA)
Routes	Oral

Dextroamphetamine (also known as dextroamphetamine sulfate, dexamphetamine sulphate, d-amphetamine, dexamphetamine, Dexedrine, Dextrostat, Dexampex, Ferndex, Oxydess II, Robese, Spancap #1, and, informally, Dex), a stereoisomer of amphetamine, is a potent central nervous system stimulant that induces the release of the neurotransmitters dopamine and norepinephrine into nerve synapses in certain areas of the brain, thus promoting nerve impulse transmission. In the majority of individuals, dextroamphetamine acts as a psychostimulant, increasing mental alertness and decreasing any sense of fatigue.

Overview and History

Dextroamphetamine, commonly abbreviated as d-amphetamine, is the dextrorotary enantiomer of amphetamine. Racemic amphetamine, which consists of equal parts dextroamphetamine and laevoamphetamine, was first synthesized under the chemical name "phenylisopropylamine" in 1887 by the Romanian chemist L. Edeleano. Amphetamine was not widely marketed until 1932, when the pharmaceutical company Smith, Kline, and French (currently known as GlaxoSmithKline) introduced it in the form of the "Benzedrine Inhaler," for combating cold symptoms. Notably, the chemical form of Benzedrine in the inhaler was the purely basic form (i.e., it was not a chloride or sulfate salt). In free-base form, amphetamine is a volatile oil, hence the efficacy of the inhalers.

Dextroamphetamine in 15mg capsules

Three years later, in 1935, the medical community became aware of the stimulant properties of amphetamine, specifically dextroamphetamine, and in 1937 Smith, Kline, and French introduced Dexedrine tablets, which consisted of pure dextroamphetamine sulfate (a salt of the basic form of D-amphetamine), under the tradename "Dexedrine". In the United States, Dexedrine tablets were approved to treat narcolepsy, attention disorders, depression, and obesity. Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and amobarbital (a barbituate) sold under the tradename "Dexamyl" and, in the 1950s, an extended release capsule (the "Spansule").

It quickly became apparent that all amphetamines, including L-amphetamine, D-amphetamine, and methamphetamine, could be abused, although these medications were not heavily controlled until 1970, when the "Comprehensive Drug Abuse Prevention and Control Act" was passed by the United States Congress. This law, which most notably formed the Bureau of Narcotics and Dangerous Drugs (the precursor to the Drug Enforcement Administration), also placed many medications into one of five classifications or "Schedules" according to their potential for substance abuse versus their medical utility. Dextroamphetamine, amphetamine, methylphenidate, and oral forms of methamphetamine (tradename "Desoxyn") were placed in schedule III of the Controlled Substances Act, while the injectable form of methamphetamine resided in schedule II. All forms of amphetamines were later placed into the more restrictive schedule II category, along with other sympathomimetics, amine or not (e.g., methylphenidate).

Virtually all synthetic sympathomimetics (and some naturally occurring ones, as well -- see ephedrine) are Scheduled/Controlled as of the current time in the United States and many other countries.

Dextroamphetamine is still widely prescribed today (see Clinical Uses, below), primarily as dextroamphetamine sulfate. Other forms of the drug include the popular ADD/ADHD medication Adderall and its generic derivatives which contain equal proportions, by weight, of dextroamphetamine sulfate, dextroamphetamine saccharate and the sulfate and saccharate salts of racemic d,l-amphetamine). The saccharate and sulfate forms differ pharmacokinetically in the rate at which they are metabolized by the body. Contrary to popular belief, methamphetamine, under the tradename "Desoxyn" can (at least technically) still be legally prescribed in the United States as of the current date (May, 2006); precisely how often it actually is prescribed is a vanishingly small number, as prescribing it more often than not warrants an immediate audit by the appropriate Agencies of the physician prescribing it; that, combined with the stigma surrounding "methamphetamine abuse", more than likely means it is rarely, if ever, prescribed.

Clinical uses

Dextroamphetamine is indicated for children and adults with attention deficit hyperactivity disorder (ADHD) or well-established narcolepsy, generally where non-pharmacological measures have proved insufficient. In some localities it has replaced Ritalin as the first-choice pharmacological treatment of ADHD, of which it is considered an effective treatment. Dexedrine is contraindicated for patients with a history of substance abuse.

Off-Label Use: Adjunct to antidepressant therapy. Studies have shown that dextroamphetamine has a very useful role in the treatment of certain categories of depression as well as other psychiatric syndromes.[1] According to the conclusion of one study on the subject, patients should not be deprived of symptom relief by these drugs. The approach to therapy should be much the same as the use of analgesics for chronic pain sufferers.[2]

Certain studies have been performed regarding possible alternate uses for antidepressant treatment for HIV patients with depression and debilitating fatigue, early stage physiotherapy for severe stroke victims, and treatment for those with methamphetamine addiction. Dextroamphetamine is also used to treat fatigue in cancer patients. Even outside clinical trials, the drug may legally be prescribed for off-label use to treat these non-approved indications. Dextroamphetamine sulfate tablets are used by the military to combat drowsiness in fighter pilots.

The drug comes in 5mg and 10mg tablets, as well as 5mg, 10mg, and 15mg capsules. The most commonly used bioavailable formulation of dextroamphetamine is dextroamphetamine sulfate, which is a salt of d-amphetamine.

Side effects

Possible adverse effects of dextroamphetamine include insomnia, reduced appetite, dependence, nervousness, restlessness, irritability, and euphoria that may be followed by fatigue and depression. There may be dryness of mouth, abdominal cramps, headache, dizziness, tremor, sweating, palpitations, increased or sometimes decreased blood pressure and altered libido. The Physician's 1991 Drug Handbook reports: "Symptoms of overdose include restlessness, tremor, hyperreflexia, tachypnea, confusion, aggressiveness, hallucinations, and panic." Note that many of the symptoms of Amphetamine psychosis are identical to the psychosis-like state which follows long-term sleep deprivation, so it remains unclear pending further studies whether or not these are solely the effect of the drug(s) themselves, or due to the long periods of sleep deprivation which is often undergone by the chronic user/abuser.

There have also been reports of growth retardation of children with long-term use, although this effect can be reduced by alternating periods of abstinence from dexedrine, often referred to as "Drug Holidays".

As dextroamphetamine is a stimulant, it is considered addictive and should be used with caution. Dextroamphetamine sulfate is a Schedule II controlled substance, and possession without prescription is illegal in the United States, and many other countries. This is true of all Schedule II substances (in the US), and sympathomimetic amines are widely known for being used/abused.

The use of dextroamphetamine for long periods of time may result in drug tolerance, and even physical dependence. Addiction is relatively uncommon when used as prescibed, such as in cases of attention deficit hyperactivity disorder and narcolepsy; however, physical habituation and physical tolerance can and generally do occur, given enough time, hence the recommendation of most physicians to recommend "drug holidays" (id est, discontinuing the use of the drug for a period of time when possible) to be taken as often as is feasible. Explaining to parents of severely hyperactive children that it would be best for them to send their children to school medicated and able to focus, and then have to endure a weekend of having them unmedicated and nearly uncontrollable, is a daunting task even for the most uncaring physician/psychiatrist, and as even taking a holiday from the drug(s) every few months is usually adequate, physician recommendations as to the period may vary, so do NOT take any of the above as medical advice for yourself or for anyone else; consult a physician.

That said, for those suffering from attention deficit hyperactivity disorder, what is more often seen is a quick buildup of tolerance to the unwanted side effects (e.g., most of the stimulant effects associated with sympathomimetic amines), without a loss of the primary desired affect, which is the ability to properly focus.

Other uses

The US Air Force uses dextroamphetamine as its "go-pill," given to pilots on long missions to help them remain focused and alert. Other branches of the US military (as well as the armed forces of foreign nations) commonly use or have dispensed dextroamphetamine to troops to prevent or treat fatigue in combat situations. Because of the propensity of dextroamphetamine to cause behavioral side effects, this use is viewed as controversial; newer stimulant medications with fewer side effects, like modafinil are being investigated for this reason.