Dextroamphetamine is a central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. In 2023, mixed amphetamine salts (Adderall) was the 15th most commonly prescribed medication in the United States, with more than 32million prescriptions.
Uses
Medical
thumb|250px|Dexedrine Spansule 5, 10, and 15 mg capsules, a sustained-release dosage form of dextroamphetamine
Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, Large recreational doses of dextroamphetamine may produce dextroamphetamine overdose. Immediate-release formulations have higher potential for abuse via insufflation (snorting) or intravenous injection due to a more favorable pharmacokinetic profile and easy crushability (especially tablets).
The reason for using crushed spansules for insufflation and injection methods is evidently due to the instant-release forms of the drug seen in tablet preparations often containing a sizable amount of inactive binders and fillers alongside the active d-amphetamine, such as dextrose. Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels. Amphetamine also interacts with , particularly monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase plasma catecholamines (i.e., norepinephrine and dopamine); The human serotonin transporter and norepinephrine transporter do not contain zinc binding sites. Norepinephrine reuptake inhibitors (NRIs) like atomoxetine prevent norepinephrine release induced by amphetamines and have been found to reduce the stimulant, euphoriant, and sympathomimetic effects of dextroamphetamine in humans.
Pharmacology
Pharmacodynamics
{| class="wikitable floatright" style="font-size:small;"
|+
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! Compound !! data-sort-type="number" | !! data-sort-type="number" | !! data-sort-type="number" | !! Ref
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| Phenethylamine || 10.9 || 39.5 || >10,000 ||
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| Levoamphetamine || 9.5 || 27.7 || ||
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| Dextromethamphetamine || 12.3–13.8 || 8.5–24.5 || 736–1,292 ||
|-
| Levomethamphetamine || 28.5 || 416 || 4,640 ||
|}
Amphetamine and its enantiomers have been identified as potent full agonists of trace amine-associated receptor 1 (TAAR1), a GPCR, discovered in 2001, that is important for regulation of monoaminergic systems in the brain. Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called VMAT2.
Dextroamphetamine (the dextrorotary enantiomer) and levoamphetamine (the levorotary enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary. Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine. not a chloride or sulfate salt.
In 1935, the medical community became aware of the stimulant properties of amphetamine, specifically the dextroamphetamine isomer, and in 1937 Smith, Kline, and French introduced tablets under the brand name Dexedrine. In the United States, Dexedrine was approved to treat narcolepsy and attention deficit hyperactivity disorder (ADHD). 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 brand name Dexamyl and, in the 1950s, an extended release capsule (the "Spansule"). Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue.
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 a government-sanctioned, recognized medical use. Internationally, it has been available under the names AmfeDyn (Italy), Curban (US), Obetrol (Switzerland), Simpamina (Italy), Dexedrine/GSK (US & Canada), Dexedrine/UCB (United Kingdom), Dextropa (Portugal), and Stild (Spain). It became popular on the mod scene in England in the early 1960s, and carried through to the Northern Soul scene in the north of England to the end of the 1970s.
In October 2010, GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).
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, "no-go pills" are used after the mission is completed, to combat the effects of the mission and "go-pills". The Tarnak Farm incident was linked by media reports to the use of this drug on long term fatigued pilots. The military did not accept this explanation, citing the lack of similar incidents. Newer stimulant medications or awakeness promoting agents with different side effect profiles, such as modafinil, are being investigated and sometimes issued for this reason. Dexedrine listed here represents the extended release "Spansule" capsule which was approved in 1976. Amphetamine sulfate tablets, now sold as Evekeo (brand), were originally sold as Benzedrine (brand) sulfate in 1935| group = "note"
! scope="col" | Brand<br />name
! scope="col" | United States<br />Adopted Name
! scope="col" class="unsortable" style="text-align:center" | (D:L) ratio
! scope="col"| Dosage<br />form
! scope="col" class="unsortable" | Marketing<br />start date
! scope="col" class="unsortable" | <small>Sources</small>
|-
| Adderall || Mixed amphetamine salts || 3:1 <small>(salts)</small><!-- DO NOT CHANGE THIS RATIO: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666194/table/table1-0269881113482532/ -->|| tablet || 1996 ||
|-
| Mydayis || Mixed amphetamine salts || 3:1 <small>(salts)</small> || capsule || 2017 ||
|-
| Adzenys XR-ODT || amphetamine || 3:1 <small>(base)</small> || ODT || 2016 ||
|-
| Dyanavel XR || amphetamine ||3.2:1 <small>(base)</small> ||suspension || 2015 ||
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| Evekeo || amphetamine sulfate || 1:1 <small>(salts)</small> || tablet || 2012 ||
|-
| Dexedrine || dextroamphetamine sulfate || 1:0 <small>(salts)</small> || capsule || 1976 || Dextroamphetamine sulfate is also available as a controlled-release (CR) capsule preparation in strengths of 5 mg, 10 mg, and 15 mg under the brand name Dexedrine Spansule, with generic versions marketed by Barr and Mallinckrodt. A bubblegum flavored oral solution is available under the brand name ProCentra, manufactured by FSC Pediatrics, which is designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL contains 5 mg dextroamphetamine. The conversion rate between dextroamphetamine sulfate to amphetamine free base is .728.
In Australia, dexamfetamine is available in bottles of 100 instant release 5 mg tablets as a generic drug or slow release dextroamphetamine preparations may be compounded by individual chemists. In the United Kingdom, it is available in 5 mg instant release sulfate tablets under the generic name dexamfetamine sulfate as well as 10 mg and 20 mg strength tablets under the brand name Amfexa. It is also available in generic dexamfetamine sulfate 5 mg/ml oral sugar-free syrup. The brand name Dexedrine was available in the United Kingdom prior to UCB Pharma disinvesting<!-- selling license to? --> the product to another pharmaceutical company, Auden Mckenzie.
Lisdexamfetamine
Dextroamphetamine is the active metabolite of the prodrug lisdexamfetamine (L-lysine-dextroamphetamine), available by the brand name Vyvanse (Elvanse in the European market and Venvanse in the Brazilian market). Dextroamphetamine is liberated from lisdexamfetamine enzymatically following contact with red blood cells. The conversion is rate-limited by the enzyme, which prevents high blood concentrations of dextroamphetamine and reduces lisdexamfetamine's drug liking and abuse potential at clinical doses. 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 chewable tablets, and in seven strengths; 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. The conversion rate between lisdexamfetamine dimesylate (Vyvanse) to dextroamphetamine base is 29.5%.
Adderall
thumb|alt=Adderall tablets|Adderall 20 mg tablets, some broken in half, with a lengthwise-folded US dollar bill along the bottom
Another pharmaceutical that contains dextroamphetamine is commonly known by the brand name Adderall.
Notes
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