Dextroamphetamine

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Dextroamphetamine
Dexamfetamine2DACS.svg
Dexamfetamine3Dan.gif
Systematic (IUPAC) name
(2S)-1-phenylpropan-2-amine
Clinical data
Trade names Dexedrine, Dextrostat, Dexamphetamine
AHFS/Drugs.com monograph
MedlinePlus a605027
Licence data US Daily Med:link
Pregnancy cat. B3 (AU) C (US)
Legal status Controlled (S8) (AU) Schedule I (CA) Class B (UK) Schedule II (US)
Dependence liability Moderate to High
Routes Oral (only medically-utilized route)
Pharmacokinetic data
Bioavailability Oral 75–100%[1]
Metabolism CYP2D6,[2] DBH,[3] FMO3,[4] XM-ligase,[5] and ACGNAT[6]
Half-life 10-12 hours[7][8]
Excretion Renal (45%);[9] urinary pH-dependent
Identifiers
CAS number 51-64-9 YesY
ATC code N06BA02
PubChem CID 5826
DrugBank DB01576
ChemSpider 5621 YesY
UNII TZ47U051FI YesY
KEGG D03740 YesY
ChEBI CHEBI:4469 YesY
ChEMBL CHEMBL612 YesY
Chemical data
Formula C9H13N 
Mol. mass 135.20622
Physical data
Density 0.913 g/cm³
Boiling point 201.5 °C (395 °F)
Solubility in water 20 mg/mL (20 °C)
 YesY (what is this?)  (verify)

Dextroamphetamine (USAN), Dexamphetamine (AAN)[10][11] and Dexamfetamine (INN and BAN) is a potent psychostimulant and amphetamine stereoisomer prescribed for the treatment of attention deficit-hyperactivity disorder (ADHD) in children and adults as well as for a sleep disorder known as narcolepsy. Dextroamphetamine is also widely used by military air forces as a 'go-pill' during fatigue-inducing mission profiles such as night-time bombing missions.

The amphetamine molecule has two stereoisomers: levoamphetamine and dextroamphetamine. Dextroamphetamine is the dextrorotatory, or "right-handed", enantiomer of the amphetamine molecule. Dextroamphetamine is available as a generic drug or under several brand names, including Dexedrine and Dextrostat, Dexamphetamine. Dextroamphetamine is also the active metabolite of the prodrug Vyvanse.

Uses[edit]

Further information: Amphetamine § Uses

Medical[edit]

Dexedrine Spansule 5, 10 and 15 mg capsules

Dextroamphetamine is used for the treatment of ADHD and narcolepsy.[12] Dextroamphetamine may be used under circumstances other than (indicated) for off-label use in the following conditions:

Investigational uses[edit]

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.[13] Such alternate uses include reduction of fatigue in cancer patients,[14] antidepressant treatment for HIV patients with depression and debilitating fatigue,[15] reduction of sedation in chronic pain patients on high doses of opiates (this also serves to potentiate the pain medicine, the "brompton cocktail" effect), and early-stage physiotherapy for severe stroke victims.[16] 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.[17]

Contraindications[edit]

Sources[7][18][19]

Side effects[edit]

By frequency[7][18][19][21][22][23]

Very common (>10% frequency)

  • Appetite loss
  • Insomnia
  • Abdominal pain

Common (1-10% frequency)

  • High heart rate
  • Palpitations
  • Tremors
  • Headache
  • Dizziness
  • Weight loss
  • Dry mouth
  • Diarrhea
  • Fever
  • Fatigue
  • Infection
  • Nausea/vomiting
  • Dyspepsia (indigestion)
  • Nervousness
  • Emotional lability

Unknown frequency adverse effects

  • Urticaria
  • Sexual dysfunction
  • Overstimulation
  • Restlessness
  • Dyskinesia
  • Tremor
  • Exacerbation of motor and phonic tics and Tourette’s syndrome
  • Hyperactivity

Serious adverse effects

Recent studies by the FDA indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, myocardial infarction, and stroke) and the use of dextroamphetamine or other ADHD stimulants in individuals with normal cardiovascular function.[24][25][26]

Overdosage[edit]

An amphetamine overdose is rarely fatal with appropriate care.[27] It can lead to different symptoms.[28][28][29] A moderate overdose may induce symptoms including irregular heartbeat, confusion, painful urination, high or low blood pressure, hyperthermia, hyperreflexia, muscle pain, severe agitation, rapid breathing, tremor, urinary hesitancy, and urinary retention.[28][29][30] An extremely large overdose may produce symptoms such as adrenergic storm, amphetamine psychosis, anuria, cardiogenic shock, cerebral hemorrhage, circulatory collapse, edema (peripheral or pulmonary), extreme fever, pulmonary hypertension, renal failure, rapid muscle breakdown, serotonin toxidrome, and stereotypy.[ref-note 1] Fatal amphetamine poisoning usually also involves convulsions and coma.[28][30]

Psychosis[edit]

Main article: Stimulant psychosis

Abuse of amphetamines can result in a stimulant psychosis which may present with a variety of symptoms (e.g. paranoia, hallucinations, delusions). A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine induced psychosis[34] states that about 5-15% of users fail to recover completely.[35] The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[34] An amphetamine psychosis may also develop occasionally as a treatment-emergent side effect.[36][36][37]

Withdrawal[edit]

While addiction is a serious risk with heavy recreational amphetamine use, it is unlikely to arise from typical medical use.[28][30][38] Tolerance is developed rapidly in amphetamine abuse; therefore, periods of extended use require increasing amounts of the drug in order to achieve the same effect.[39] According to a Cochrane Collaboration review on withdrawal in highly dependent amphetamine and methamphetamine abusers, "when chronic heavy users abruptly discontinue amphetamine use, many report a time-limited withdrawal syndrome that occurs within 24 hours of their last dose."[40] This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for 3–4 weeks with a marked "crash" phase occurring during the first week.[40] Amphetamine withdrawal symptoms can include fatigue, dysphoric mood, increased appetite, vivid or lucid dreams, hypersomnia or insomnia, increased movement or decreased movement, anxiety, and drug craving.[40] The review suggested that withdrawal symptoms are associated with the degree of dependence, suggesting that therapeutic use would result in far milder discontinuation symptoms.[40] The USFDA does not indicate the presence of withdrawal symptoms following discontinuation of pharmaceutical amphetamine use after an extended period at therapeutic doses.[41][42][43]

Pharmacology[edit]

Pharmacodynamics[edit]

The main section for this topic is on the page Amphetamine, in the section Pharmacodynamics.

Pharmacodynamics of amphetamine enantiomers in a dopamine neuron

A pharmacodynamic model of amphetamine and TAAR1
via AADC
Amphetamine enters the presynaptic neuron across the neuronal membrane or through DAT. Once inside, it binds to TAAR1 or enters synaptic vesicles through VMAT2. When amphetamine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol (yellow-orange area). When amphetamine binds to TAAR1, it reduces dopamine receptor firing rate via potassium channels and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT phosphorylation. PKA-phosphorylation causes DAT to withdraw into the presynaptic neuron (internalize) and cease transport. PKC-phosphorylated DAT may either operate in reverse or, like PKA-phosphorylated DAT, internalize and cease transport.


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.[44][45] Activation of TAAR1 increases cAMP production via adenylyl cyclase activation and inhibits the function of the dopamine transporter, norepinephrine transporter, and serotonin transporter, as well as inducing the release of these monoamine neurotransmitters (effluxion).[44][46][47] Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called VMAT2.[48] When amphetamine is taken up by VMAT2, the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.[48]

Dextroamphetamine (the dextrorotary enantiomer) and levoamphetamine (the levorotary enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary.[30][45] Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine.[45] Consequently, dextroamphetamine produces roughly three to four times more central nervous system (CNS) stimulation than levoamphetamine;[30][45] however, levoamphetamine has slightly greater cardiovascular and peripheral effects.[30]

Related endogenous compounds[edit]

Further information: Trace amines

Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring molecules produced in the human body and brain.[47][49] Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and N-methylphenethylamine, an isomer of amphetamine (i.e., identical molecular formula).[47][49] In humans, phenethylamine is produced in the body directly from phenylalanine by the same enzyme that converts L-DOPA into dopamine, aromatic amino acid decarboxylase.[49] In turn, N‑methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, which the same enzyme that metabolizes norepinephrine into adrenaline.[49] Like amphetamine, both phenethylamine and N‑methylphenethylamine regulate monoamine neurotransmission via TAAR1;[47] however, unlike amphetamine, both of these substances are broken down by monoamine oxidase, and therefore have a shorter half-life than amphetamine.[49]

Pharmacokinetics[edit]

Amphetamine is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine.[50] However, oral availability varies with gastrointestinal pH.[51] Dextroamphetamine is a weak base with a pKa of 9–10;[2] consequently, when the pH is basic, more of the drug is in its lipid soluble free base form, and more is absorbed through the lipid-rich cell membranes of the gut epithelium.[2][51] Conversely, an acidic pH means the drug is predominantly in its water soluble cationic form, and less is absorbed.[2][51]

Approximately 15–40% of dextroamphetamine circulating in the bloodstream is bound to plasma proteins.[52]

The half-life of dextroamphetamine varies with urine pH.[2] At normal urine pH, the half-life of dextroamphetamine is 9–11 hours.[2] An acidic diet will reduce the half-life to 8–11 hours, while an alkaline diet will increase the range to 16–31 hours.[53][54] The immediate-release and extended release variants of dextroamphetamine salts reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively.[2] Dextromphetamine is eliminated via the kidneys, with 30–40% of the drug being excreted unchanged at normal urinary pH.[2] When the urinary pH is basic, more of the drug is in its poorly water soluble free base form, and less is excreted.[2] When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to as much as 75%, depending mostly upon whether urine is too basic or acidic, respectively.[2] Amphetamine is usually eliminated within two days of the last oral dose.[53] Apparent half-life and duration of effect increase with repeated use and accumulation of the drug.[55]

CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase, butyrate-CoA ligase, and glycine N-acyltransferase are the enzymes known to metabolize amphetamine or its metabolites in humans.[2][3][4][5][6][56] Amphetamine has a variety of excreted metabolic products, including 4-hydroxyamfetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone.[2][53][57] Among these metabolites, the active sympathomimetics are 4‑hydroxyamphetamine,[58] 4‑hydroxynorephedrine,[59] and norephedrine.[60]

The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.[2][53] The known pathways include:[2][4][57]

Metabolic pathways of amphetamine

Graphic of several routes of amphetamine metabolism
Para-
Hydroxylation
Para-
Hydroxylation
Para-
Hydroxylation
Beta-
Hydroxylation
Beta-
Hydroxylation
Oxidative
Deamination
Oxidation
Glycine
Conjugation
The primary active metabolites of amphetamine are 4-hydroxyamphetamine and norephedrine;[57] however, most of an administered dose is excreted as amphetamine itself and the inactive metabolites.[2] Benzoic acid is metabolized by butyrate-CoA ligase into an intermediate product, benzoyl-CoA,[5] which is then metabolized by glycine N-acyltransferase into hippuric acid.[6]

History, society, and culture[edit]

Racemic amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by the Romanian chemist Lazar Edeleanu.[61] 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 dexamfetamine, and in 1937 Smith, Kline, and French introduced tablets under the tradename Dexedrine.[62] In the United States, Dexedrine was approved to treat narcolepsy, attention disorders, depression, and obesity. In Canada, epilepsy and parkinsonism were also approved indications.[63] Dexamfetamine 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 dexamfetamine and amobarbital (a barbiturate) sold under the tradename Dexamyl and, in the 1950s, an extended release capsule (the "Spansule").[64]

It quickly became apparent that dexamfetamine 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. Dexamfetamine, 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.[65] 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).[66]

In October 2010, GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).[67]

The U.S. Air Force uses dexamfetamine 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".[68][69][70][71] 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.[69]

Formulations[edit]

Pharmaceuticals
Brand
name
United States
Adopted Name
(D:L) ratio
of salts
Dosage
form
Source
Adderall 3:1 tablet [72][73]
Adderall XR 3:1 capsule [72][73]
Dexedrine dextroamphetamine sulfate 1:0 capsule [72][73]
ProCentra dextroamphetamine sulfate 1:0 liquid [73]
Vyvanse lisdexamfetamine dimesylate 1:0 capsule [72][74]
Zenzedi dextroamphetamine sulfate 1:0 tablet [73]
 
An image of the lisdexamphetamine compound
The skeletal structure of lisdexamfetamine

Dextroamphetamine sulfate[edit]

Dexamphetamine 5 mg generic name tablets

In the United States, an instant-release (IR) tablet preparation of dextroamphetamine sulfate is available under the brand name Dextrostat, in 5 mg and 10 mg strengths,[75] with generic versions marketed by Barr (Teva Pharmaceutical Industries), Mallinckrodt Pharmaceuticals and Wilshire Pharmaceuticals. 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 dexamfetamine.[76]

In Australia, dexamfetamine is available in bottles of 100 instant release 5 mg tablets as a generic drug.[77] or slow release dexamfetamine preparations may be compounded by individual chemists.[78] Similarly, in the United Kingdom it is only available in 5 mg instant release sulfate tablets under the generic name dexamfetamine sulphate having had been available under the brand name Dexedrine prior to UCB Pharma disinvesting the product to another pharmaceutical company (Auden Mckenzie).[79]

Lisdexamfetamine[edit]

Main article: Lisdexamfetamine

Dexamfetamine is the active metabolite of the prodrug lisdexamfetamine (L-lysine-dextroamphetamine), available by the brand name Vyvanse (Lisdexamfetamine dimesylate). Lisdexamfetamine is metabolised in the gastrointestinal tract, while dextroamphetamine's metabolism is hepatic.[80] Lisdexamfetamine is therefore an inactive compound until it is converted into an active compound by the digestive system. Vyvanse is marketed as once-a-day dosing as it provides a slow release of dexamfetamine 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 dimesylate to dextroamphetamine base is 0.2948,[81] thus a 30 mg-strength Vyvanse capsule is molecularly equivalent to 8.844 mg dexamfetamine base.

Amphetamine salts (Adderall)[edit]

Adderall IR 30 mg tablets
Main article: Adderall

Another pharmaceutical that contains dextroamphetamine is commonly known by the brand name Adderall. The drug formulation of Adderall, including both the immediate release (IR) and extended release (XR) forms, is:

One-quarter racemic (d,l-)amphetamine aspartate monohydrate
One-quarter dextroamphetamine saccharate
One-quarter dextroamphetamine sulfate
One-quarter racemic (d,l-)amphetamine sulfate

Adderall is roughly three-quarters dextroamphetamine, with it accounting for 72.7% of the amphetamine base in Adderall (the remaining percentage is levoamphetamine). The salt ratio, as noted above, is 75%:25% or 3:1 dextroamphetamine to levoamphetamine.

References[edit]

  1. ^ Pharmacology. "Dextromphetamine". DrugBank. Retrieved 5 November 2013. 
  2. ^ a b c d e f g h i j k l m n o "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 12–13. Retrieved 30 December 2013. 
  3. ^ a b Lemke TL, Williams DA, Roche VF, Zito W (2013). Foye's Principles of Medicinal Chemistry (7th ed. ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 648. ISBN 1609133455. "Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine." 
  4. ^ a b c Krueger SK, Williams DE (June 2005). "Mammalian flavin-containing monooxygenases: structure/function, genetic polymorphisms and role in drug metabolism". Pharmacol. Ther. 106 (3): 357–387. doi:10.1016/j.pharmthera.2005.01.001. PMC 1828602. PMID 15922018. 
  5. ^ a b c Substrate/Product. "butyrate-CoA ligase". BRENDA. Technische Universität Braunschweig. Retrieved 7 May 2014. 
  6. ^ a b c Substrate/Product. "glycine N-acyltransferase". BRENDA. Technische Universität Braunschweig. Retrieved 7 May 2014. 
  7. ^ a b c d "Dexedrine Medication Guide". United States Food and Drug Administration. May 2013. p. 1. Retrieved 2 November 2013. 
  8. ^ "Dextroamphetamine Sulfate (dextroamphetamine sulfate) Tablet [ETHEX Corporation]". DailyMed. ETHEX Corporation. February 2008. Retrieved 8 November 2013. 
  9. ^ "dextrostat (dextroamphetamine sulfate) tablet [Shire US Inc.]". DailyMed. Wayne, PA: Shire US Inc. August 2006. Retrieved 8 November 2013. 
  10. ^ Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.  edit
  11. ^ Samson, L; Cosh, D; Cutajar, M; Hughes, J; Lynch, M; Martin, G; McKinnon, R; McLachlan, A; Philips, A; Roller, L, ed. (2012). Australian Pharmaceutical Formulary and Handbook (22nd ed.). Deakin West, ACT: Pharmaceutical Society of Australia. ISBN 9780646570198.  edit
  12. ^ First line treatments U.S. Food and Drug Administration | GlaxoSmithKline Prescribing Information
  13. ^ Warneke L (1990). "Psychostimulants in psychiatry". Can J Psychiatry 35 (1): 3–10. PMID 2180548. 
  14. ^ Breitbart W, Alici Y (2010). "Psychostimulants for cancer-related fatigue.". J Natl Compr Canc Netw 8 (8): 933–42. PMID 20870637. 
  15. ^ Wagner G, Rabkin R (2000). "Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial". J Clin Psychiatry 61 (6): 436–40. doi:10.4088/JCP.v61n0608. PMID 10901342. 
  16. ^ Martinsson L, Yang X, Beck O, Wahlgren N, Eksborg S (2003). "Pharmacokinetics of dextroamphetamine in acute stroke". Clin Neuropharmacol 26 (5): 270–6. doi:10.1097/00002826-200309000-00012. PMID 14520168. 
  17. ^ Butefisch CM et al. (2002). "Modulation of Use-Dependent Plasticity by D-Amphetamine". Annals of Neurology 51 (1): 59–68. doi:10.1002/ana.10056. PMID 11782985. 
  18. ^ a b c "DEXTROAMPHETAMINE SULFATE tablet [Barr Laboratories Inc.]". DailyMed. Barr Laboratories Inc. October 2013. Retrieved 7 November 2013. 
  19. ^ a b c "dextroamphetamine (Rx) - Dexedrine, Liquadd, more...". Medscape Reference. WebMD. Retrieved 7 November 2013. 
  20. ^ RxList | Dexedrine (Dextroamphetamine)
  21. ^ Vitiello B (2008). "Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function". Child Adolesc Psychiatr Clin N Am 17 (2): 459–74, xi. doi:10.1016/j.chc.2007.11.010. PMC 2408826. PMID 18295156. 
  22. ^ Dextroamphetamine (Oral Route) | MayoClinic.com
  23. ^ Vitiello B (2008). "Understanding the Risk of Using Medications for ADHD with Respect to Physical Growth and Cardiovascular Function". Child Adolesc Psychiatr Clin N Am 17 (2): 459–74, xi. doi:10.1016/j.chc.2007.11.010. PMC 2408826. PMID 18295156. 
  24. ^ "ADHD Medications and Risk of Stroke In Young and Middle-Aged Adults". Retrieved 11 June 2013. 
  25. ^ "ADHD Medications and Risk of Serious Coronary Heart Disease in Young and Middle-Aged Adults". Retrieved 11 June 2013. 
  26. ^ "Attention Deficit Hyperactivity Disorder Medications and Risk of Serious Cardiovascular Disease in Children and Youth". Retrieved 11 June 2013. 
  27. ^ a b Spiller HA, Hays HL, Aleguas A (June 2013). "Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management". CNS Drugs 27 (7): 531–543. doi:10.1007/s40263-013-0084-8. PMID 23757186. 
  28. ^ a b c d e f "Adderall XR Prescribing Information". United States Food and Drug Administration. June 2013. p. 11. Retrieved 7 October 2013. 
  29. ^ a b c "Adderall XR Prescribing Information". United States Food and Drug Administration. June 2013. pp. 4–8. Retrieved 7 October 2013. 
  30. ^ a b c d e f g Westfall DP, Westfall TC (2010). "Miscellaneous Sympathomimetic Agonists". In Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's Pharmacological Basis of Therapeutics (12th ed.). New York: McGraw-Hill. ISBN 9780071624428. 
  31. ^ O'Connor PG (February 2012). "Amphetamines". Merck Manual for Health Care Professionals. Merck. Retrieved 8 May 2012. 
  32. ^ Albertson TE (2011). "Amphetamines". In Olson KR, Anderson IB, Benowitz NL, Blanc PD, Kearney TE, Kim-Katz SY, Wu AHB. Poisoning & Drug Overdose (6th ed.). New York: McGraw-Hill Medical. pp. 77–79. ISBN 9780071668330. 
  33. ^ Oskie SM, Rhee JW (11 February 2011). "Amphetamine Poisoning". Emergency Central. Unbound Medicine. Retrieved 11 June 2013. 
  34. ^ a b Shoptaw SJ, Kao U, Ling W (2009). "Treatment for amphetamine psychosis (Review)". Cochrane Database of Systematic Reviews (1). 
  35. ^ Hofmann FG. A handbook on drug and alcohol abuse: the biomedical aspects. 2nd Edition. New York: Oxford University Press, 1983.
  36. ^ a b Berman, SM.; Kuczenski, R.; McCracken, JT.; London, ED. (Feb 2009). "Potential adverse effects of amphetamine treatment on brain and behavior: a review". Mol Psychiatry 14 (2): 123–42. doi:10.1038/mp.2008.90. PMC 2670101. PMID 18698321. 
  37. ^ . Merck Sharpe and Dohme http://www.merck.com/mmpe/sec15/ch198/ch198k.htmlAmphetamines. Retrieved 27 November 2013.  Missing or empty |title= (help)
  38. ^ Stolerman IP (2010). Stolerman IP, ed. Encyclopedia of Psychopharmacology. Berlin; London: Springer. p. 78. ISBN 9783540686989. "Although [substituted amphetamines] are also used as recreational drugs, with important neurotoxic consequences when abused, addiction is not a high risk when therapeutic doses are used as directed." 
  39. ^ "Amphetamines: Drug Use and Abuse". Merck Manual Home Edition. Merck. February 2003. Archived from the original on 17 February 2007. Retrieved 28 February 2007. 
  40. ^ a b c d Shoptaw SJ, Kao U, Heinzerling K, Ling W (2009). "Treatment for amphetamine withdrawal". In Shoptaw SJ. Cochrane Database Syst. Rev. (2): CD003021. doi:10.1002/14651858.CD003021.pub2. PMID 19370579. "
    The prevalence of this withdrawal syndrome is extremely common (Cantwell 1998; Gossop 1982) with 87.6% of 647 individuals with amphetamine dependence reporting six or more signs of amphetamine withdrawal listed in the DSM when the drug is not available (Schuckit 1999)...Withdrawal symptoms typically present within 24 hours of the last use of amphetamine, with a withdrawal syndrome involving two general phases that can last 3 weeks or more. The first phase of this syndrome is the initial “crash” that resolves within about a week (Gossop 1982;McGregor 2005)..."
     
  41. ^ "Adderall IR Prescribing Information". United States Food and Drug Administration. March 2007. Retrieved 4 November 2013. 
  42. ^ "Dexedrine Medication Guide". United States Food and Drug Administration. May 2013. Retrieved 4 November 2013. 
  43. ^ "Adderall XR Prescribing Information". United States Food and Drug Administration. June 2013. Retrieved 4 November 2013. 
  44. ^ a b Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK (December 2001). "Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor". Mol. Pharmacol. 60 (6): 1181–8. doi:10.1124/mol.60.6.1181. PMID 11723224. 
  45. ^ a b c d Lewin AH, Miller GM, Gilmour B (December 2011). "Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class". Bioorg. Med. Chem. 19 (23): 7044–7048. doi:10.1016/j.bmc.2011.10.007. PMC 3236098. PMID 22037049. 
  46. ^ Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C (July 2001). "Trace amines: identification of a family of mammalian G protein-coupled receptors". Proc. Natl. Acad. Sci. U.S.A. 98 (16): 8966–71. Bibcode:2001PNAS...98.8966B. doi:10.1073/pnas.151105198. PMC 55357. PMID 11459929. 
  47. ^ a b c d Miller GM (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–76. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468. 
  48. ^ a b Eiden LE, Weihe E (January 2011). "VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse". Ann. N. Y. Acad. Sci. 1216: 86–98. doi:10.1111/j.1749-6632.2010.05906.x. PMID 21272013. 
  49. ^ a b c d e Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. "Fig. 2. Synthetic and metabolic pathways for endogenous and exogenously administered trace amines and sympathomimetic amines...
    Trace amines are metabolized in the mammalian body via monoamine oxidase (MAO; EC 1.4.3.4) (Berry, 2004) (Fig. 2)...It deaminates primary and secondary amines that are free in the neuronal cytoplasm but not those bound in storage vesicles of the sympathetic neurone...
    Thus, MAO inhibitors potentiate the peripheral effects of indirectly acting sympathomimetic amines. It is not often realized, however, that this potentiation occurs irrespective of whether the amine is a substrate for MAO. An α-methyl group on the side chain, as in amphetamine and ephedrine, renders the amine immune to deamination so that they are not metabolized in the gut. Similarly, β-PEA would not be deaminated in the gut as it is a selective substrate for MAO-B which is not found in the gut...
    Brain levels of endogenous trace amines are several hundred-fold below those for the classical neurotransmitters noradrenaline, dopamine and serotonin but their rates of synthesis are equivalent to those of noradrenaline and dopamine and they have a very rapid turnover rate (Berry, 2004). Endogenous extracellular tissue levels of trace amines measured in the brain are in the low nanomolar range. These low concentrations arise because of their very short half-life,..."
     
  50. ^ Pharmacology. "Dextroamphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 5 November 2013. 
  51. ^ a b c "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 8–10. Retrieved 30 December 2013. 
  52. ^ Pharmacology. "Amphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 5 November 2013. 
  53. ^ a b c d Biomedical Effects and Toxicity. "Amphetamine". Pubchem Compound. National Center for Biotechnology Information. Retrieved 12 October 2013. 
  54. ^ Biological Half-Life. "AMPHETAMINE". United States National Library of Medicine - Toxnet. Hazardous Substances Data Bank. Retrieved 5 January 2014. "Concentrations of (14)C-amphetamine declined less rapidly in the plasma of human subjects maintained on an alkaline diet (urinary pH > 7.5) than those on an acid diet (urinary pH < 6). Plasma half-lives of amphetamine ranged between 16-31 hr & 8-11 hr, respectively, & the excretion of (14)C in 24 hr urine was 45 & 70%." 
  55. ^ Richard RA (1999). Route of Administration. "Chapter 5—Medical Aspects of Stimulant Use Disorders". National Center for Biotechnology Information Bookshelf. Treatment Improvement Protocol 33. Substance Abuse and Mental Health Services Administration. 
  56. ^ Enzymes. "Amphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 30 September 2013. 
  57. ^ a b c Santagati NA, Ferrara G, Marrazzo A, Ronsisvalle G (September 2002). "Simultaneous determination of amphetamine and one of its metabolites by HPLC with electrochemical detection". J. Pharm. Biomed. Anal. 30 (2): 247–255. doi:10.1016/S0731-7085(02)00330-8. PMID 12191709. 
  58. ^ Compound Summary. "p-Hydroxyamphetamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  59. ^ Compound Summary. "p-Hydroxynorephedrine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  60. ^ Compound Summary. "Phenylpropanolamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  61. ^ Help For Dexedrine Addicts | Dexedrine Rehab Centers For Addicts
  62. ^ "Dexedrine". Medic8. Retrieved 27 November 2013. 
  63. ^ Dextroamphetamine: Canadian Drug Monograph
  64. ^ Information on Dexedrine: A Quick Review | Weitz & Luxenberg
  65. ^ Prescription Forgery | Handwriting Services International
  66. ^ Pharmaceutical Manufacturing Encyclopedia (2nd edition), Marshall Sittig, Volume 1, Noyes Publications ISBN 978-0-8155-1144-1
  67. ^ "Dexedrine FAQs". 
  68. ^ http://www.nbcnews.com/id/3071789/ns/us_news-only/t/go-pills-war-drugs/
  69. ^ a b Air Force scientists battle aviator fatigue
  70. ^ Emonson, DL; Vanderbeek, RD (1995). "The use of amphetamines in U.S. Air Force tactical operations during Desert Shield and Storm". Aviation, space, and environmental medicine 66 (3): 260–3. PMID 7661838. 
  71. ^ ‘Go pills’: A war on drugs?, msnbc, 9 January 2003
  72. ^ a b c d Description, Synonyms, Brand names, and Brand mixtures. "Amphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 13 October 2013. 
  73. ^ a b c d e "National Drug Code Amphetamine Search Results". National Drug Code Directory. United States Food and Drug Administration. Archived from the original on 7 February 2014. Retrieved 16 December 2013. 
  74. ^ Identification. "Lisdexamfetamine". Drugbank. University of Alberta. 8 February 2013. Retrieved 13 October 2013. 
  75. ^ http://www.goodrx.com/dextrostat/images
  76. ^ FSC Laboratories: ProCentra (dextroamphetamine sulfate | 5 mg/5 mL Oral Solution)
  77. ^ Australian Prescriber | Stimulant treatment for attention deficit hyperactivity disorder
  78. ^ http://www0.health.nsw.gov.au/PublicHealth/Pharmaceutical/adhd/faqs.asp
  79. ^ "Red/Amber News Iss. 22", p2. Interface Pharmacist Network Specialist Medicines (IPNSM). www.ipnsm.hscni.net. Retrieved 20 April 2012.
  80. ^ FDA Approval of Vyvanse Pharmacological Reviews Pages 18 and 19
  81. ^ Mohammad Mohammadi; Shahin Akhondzadeh (17 September 2011). "Advances and considerations in attention-deficit/hyperactivity disorder pharmacotherapy". Acta medica Iranica 49 (8): 491. PMID 22009816. Retrieved 12 March 2014. 

Notes[edit]

  1. ^ Free-base form amphetamine is a volatile oil, hence the efficacy of the inhalers.

Reference notes[edit]

  1. ^ [27][28][29][30][31][32][33]

External links[edit]