|Systematic (IUPAC) name|
|CAS number||51-63-8 (sulfate), 1462-73-3 (hydrochloride)|
|Half life||10–28 hours
(Average ~12 hours)
|Pregnancy cat.||B3(AU) C(US)|
|Legal status||Controlled (S8) (AU) Schedule III (CA) ? (UK) Schedule II (US)|
|Routes||Oral, Intravenous, Sublingual, Vaporized, Insufflated, Rectal|
(what is this?) (verify)|
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus in association with decreased fatigue and decreased appetite. Drugs with similar psychoactive properties can be referred to or described as "amphetamine analogues", "amphetamine-like", or having "amphetaminergic" effects. Enantiomerically pure dextroamphetamine is more potent than racemic amphetamine and has stimulant properties similar to racemic methamphetamine, though less potent and neurotoxic.
Dextroamphetamine is the dextrorotary or "Right-handed" stereoisomer of the amphetamine molecule. The amphetamine molecule has 2 stereoisomers: levo-amphetamine and dextro-amphetamine. Names for dextroamphetamine include d-amphetamine, dexamphetamine, dexamfetamine, and (S)-(+)-amphetamine, and brand names for dextroamphetamine include Dexedrine and Dextrostat. It is the active metabolite of the prodrug, lisdexamfetamine, which is known by its brand name Vyvanse, and makes up approximately 72% of ADHD drug Adderall , which consists of dextroamphetamine and amphetamine salts combination. In addition, dextroamphetamine is an active metabolite of several older N-substituted amphetamine prodrugs used as anorectics, such as clobenzorex (Asenlix), benzphetamine (Didrex), and amphetaminil (Aponeuron).
Racemic amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by the Romanian chemist Lazar Edeleanu. It was not widely marketed until 1932, when the pharmaceutical company Smith, Kline & French (now known as GlaxoSmithKline) introduced it in the form of the Benzedrine inhaler for use as a bronchodilator. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base,[n 1] not a chloride or sulfate salt.
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 tablets under the tradename Dexedrine. In the United States, Dexedrine was 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 barbiturate) sold under the tradename Dexamyl and, in the 1950s, an extended release capsule (the "Spansule").
It quickly became apparent that dextroamphetamine and other amphetamines had a high potential for misuse, although they were not heavily controlled until 1970, when the Comprehensive Drug Abuse Prevention and Control Act was passed by the United States Congress. Dextroamphetamine, along with other sympathomimetics, was eventually classified as Schedule II, the most restrictive category possible for a drug with recognized medical use.
Internationally, it has been available under the names AmfeDyn (Italy), Curban (US), Obetrol (Switzerland), Simpamina (Italy), Dexedrine (US), Dextropa (Portugal), and Stild (Spain).
Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma. Agitated state. Patients with a history of drug abuse. During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crisis may result).
Physical effects of dextroamphetamine can include anorexia, hyperactivity, dilated pupils, blood shot eyes, flushing, restlessness, dry mouth, bruxism, headache, tachycardia, bradycardia, tachypnea, hypertension, hypotension, fever, diaphoresis, diarrhea, constipation, blurred vision, aphasia, dizziness, twitching, insomnia, numbness, palpitations, arrhythmias, tremors, dry and/or itchy skin, acne, pallor, convulsions, and in rare cases (or in cases of abuse) coma, stroke, heart attack and death.  
Psychological effects can include euphoria, anxiety, increased libido, alertness, concentration, energy, self-esteem, self-confidence, sociability, irritability, aggression, psychosomatic disorders, psychomotor agitation, hubris, excessive feelings of power and invincibility, repetitive and obsessive behaviors, paranoia, and with chronic and/or high doses, amphetamine psychosis can occur. The long term effects of amphetamine use on the neural development of children have not been established.
Withdrawal symptoms from dextroamphetamine primarily consist of mental fatigue, mental depression and an increased appetite. Symptoms may last for days with occasional use and weeks or months with chronic use, with severity dependent on the length of time and the amount of dextroamphetamine taken. Withdrawal symptoms may also include anxiety, agitation, excessive sleep, vivid or lucid dreams (deep REM sleep), suicidal thoughts and psychosis.
The Physician's 1991 Drug Handbook reports: "Symptoms of overdose include restlessness, tremor, hyperreflexia, tachypnea, confusion, aggressiveness, hallucinations, and panic." Dilated pupils are common with high doses. Repeated high doses may lead to manifestations of acute psychosis.
The fatal dose in humans is not precisely known, but in various species of rat generally ranges between 50 and 100 mg/kg, or a factor of 100 over what is required to produce noticeable psychological effects. Although the symptoms seen in a fatal overdose are similar to those of methamphetamine, their mechanisms are not identical, as some substances which inhibit dextroamphetamine toxicity do not do so for methamphetamine.
An extreme symptom of overdose is amphetamine psychosis, characterized by vivid visual, auditory, and sometimes tactile hallucinations. Many of its symptoms are identical to the psychosis-like state which follows long-term sleep deprivation, so it remains unclear whether these are solely the effects of the drug, or due to the long periods of sleep deprivation which are often undergone by the chronic user. Amphetamine psychosis, however, is extremely rare in individuals taking oral amphetamines at therapeutic doses; it is usually seen in cases of prolonged or high-dose intravenous (IV) for non-medicinal uses.
In the United States, an instant release tablet preparation of the salt dextroamphetamine sulfate is available under the brand names Dexedrine and Dextrostat, in 5 mg and 10 mg strengths, and as a capsule preparation of controlled release dextroamphetamine sulfate, under the brand names Dexedrine SR and Dexedrine Spansule, in the strengths of 5 mg, 10 mg, and 15 mg. There is also an oral bubblegum flavored solution available under the brand name ProCentra, in the strength of 5mg/5ml, manufactured by Tiber Labs.
Dextroamphetamine is the active metabolite of the prodrug lisdexamfetamine (L-lysine-d-amphetamine), available by the trademark name Vyvanse. Lisdexamfetamine is metabolised in the gastrointestinal tract, while dextroamphetamine's metabolism is hepatic. Lisdexamfetamine is therefore an inactive compound until it is converted into an active compound by the digestive system. Although still rated as a Schedule II drug by the U.S. Drug Enforcement Administration, lisdexamfetamine has a slower onset and its route of administration is limited to being taken orally, unlike dextroamphetamine, Adderall, and methylphenidate, which can be insufflated to achieve a faster onset with a higher bioavailability. Vyvanse is marketed as once-a-day dosing as it provides a slow release of dextroamphetamine into the body. Vyvanse is available as capsules, and in six strengths; 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. The conversion rate of lisdexamfetamine to dextroamphetamine base is 0.2948, so a 30 mg-strength Vyvanse capsule is molecularly equivalent to 8.844 mg dextroamphetamine base.
Another pharmaceutical that contains dextroamphetamine is Adderall. The drug formulation of Adderall (both controlled and instant release forms) is:
Adderall is roughly three-quarters dextroamphetamine, with it accounting for 72.7% of the amphetamine base in Adderall (the remaining percentage is levoamphetamine). An experiment with rats suggested, Adderall’s inclusion of levoamphetamine provides the pharmaceutical with a quicker onset and longer clinical effect compared to pharmaceuticals exclusively formulated of dextroamphetamine. One study has shown that although the human brain usually has a preference for dextroamphetamine over levoamphetamine, certain children have a better clinical response to levoamphetamine. Dextroamphetamine induces more euphoria, whereas levoamphetamine induces more depression.
The overall greater potency of the dextro form to central actions suggests that this form may have a higher potential for abuse.
Though such use remains out of the mainstream, dextroamphetamine has been successfully applied in the treatment of certain categories of depression as well as other psychiatric syndromes. Such alternate uses include reduction of fatigue in cancer patients, antidepressant treatment for HIV patients with depression and debilitating fatigue, and early stage physiotherapy for severe stroke victims. If physical therapy patients take dextroamphetamine while they practice their movements for rehabilitation, they may learn to move much faster than without dextroamphetamine, and in practice sessions with shorter lengths.
The U.S. Air Force uses dextroamphetamine as one of its "go pills", given to pilots on long missions to help them remain focused and alert. Conversely, the Air Force also issues "no-go pills"; prescription sedatives used after the mission to calm down.  The Tarnak Farm incident was linked by media reports to the use of this drug on long term fatigued pilots. A military tribunal did not accept this explanation, citing the lack of similar incidents. Newer stimulant medications or awakeness promoting agents with fewer side effects, such as modafinil are being investigated and sometimes issued for this reason.
During the Vietnam War, Special Units of the US Military, such as MACV-SOG, were issued dextroamphetamine tablets. Due to the threat of misuse, these tablets were given to the Commanding Officer of the unit, and given out when needed.
Along with amphetamine and methylphenidate, dextroamphetamine has been used as a recreational stimulant drug that provides euphoria, and also as an unprescribed study aid or social aid. According to the National Institute on Drug Abuse, a large percentage of American college students have reported stimulant use for non-medicinal purposes.
Scientific findings have established that dextroamphetamine administration increases the activity of the phosphoinositol cycle via an indirect release of dopamine and noradrenaline. These results are the first time that this has been confirmed in humans. Because dextroamphetamine is a substrate analog at monoamine transporters, at all doses, dextroamphetamine prevents the re-uptake of these neurotransmitters by competing with endogenous monoamines for uptake. Transporter inhibition causes monoamines to remain in the synaptic cleft for a prolonged period (amphetamine inhibits monoamine reuptake in rats with a norepinephrine to dopamine ratio (NE:DA) of 1:1 and a norepinephrine to 5-hydroxytryptamine ratio (NE:5-HT) of about 100:1).
At higher doses, when the concentration of dextroamphetamine is sufficient, the drug can trigger direct release of norepinephrine and dopamine from the cytoplasmic transmitter pool, that is, dextroamphetamine will cause norepinephrine and dopamine efflux via transporter proteins, functionally reversing transporter action, which triggers a cascading release of catecholamines. This inversion leads to a release of large amounts of these neurotransmitters from the cytoplasm of the presynaptic neuron into the synapse, causing increased stimulation of post-synaptic receptors, inducing euphoria. Dextroamphetamine releases monoamines in rats with selectivity ratios of about NE:DA = 1:3.5 and NE:5-HT = 1:250, meaning that NE and DA are readily released, but release of 5-HT occurs at a 1/4 ration than of NE:DA.
Dextroamphetamine increases dopamine release in the prefrontal cortex; activation of the dopamine-2 receptors inhibits glutamate release in the prefrontal cortex. Activation of the dopamine-1 receptors in the prefrontal cortex, however, results in elevated glutamate levels in the nucleus accumbens. An increase of the glutamate levels in the nucleus accumbens is the reason that dextroamphetamine has an ability to increase locomotor activity in rats. Serotonin also plays a role in dextroamphetamine's effect on glutamate levels; however, at therapeutic doses, dextroamphetamine has minuscule effect on the serotonin transporter (SERT).
On average, about one half of a given dose is eliminated unchanged in the urine, while the other half is broken down into various metabolites (mostly benzoic acid). However, the drug's half-life is highly variable because the rate of excretion is very sensitive to urinary pH. Under alkaline conditions, direct excretion is negligible and 95%+ of the dose is metabolized. Having an alkaline stomach will cause the drug to be absorbed faster through the stomach resulting in a higher blood level concentration of amphetamine. Having an alkaline bladder causes the drug to be excreted very slowly. It is possible with acute doses of sodium bicarbonate dissolved in water during amphetamine's course in the body for the half-life of the drug to last about 24 hours, with after effects lasting another 10 hours. The main metabolic pathway is dextroamphetamine phenylacetone benzoic acid hippuric acid. Another pathway, mediated by enzyme CYP2D6, is dextroamphetamine p-hydroxyamphetamine p-hydroxynorephedrine. Although p-hydroxyamphetamine is a minor metabolite (~5% of the dose), it may have significant physiological effects as a norepinephrine analogue.
Subjective effects are increased by larger doses, however, over the course of a given dose there is a noticeable divergence between such effects and drug concentration in the blood. In particular, mental effects peak before maximal blood levels are reached, and decline as blood levels remain stable or even continue to increase. This indicates a mechanism for development of acute tolerance, perhaps distinct from that seen in chronic use.