View source for Chemistry:Dextroamphetamine

{{Short description|CNS stimulant and isomer of amphetamine}}
{{Infobox drug
| Verifiedfields     = changed
| Watchedfields      = changed
| verifiedrevid      = 596899008
| INN                = dexamfetamine
| type               = <!-- empty -->
| image              = D-amphetamine.svg
| width              = 200
| alt                =
| caption            = <!-- Clinical data -->
| pronounce          = {{IPAc-en|ˌ|d|ɛ|k|s|t|r|əʊ|æ|m|ˈ|f|ɛ|t|ə|m|iː|n}}
| tradename          =  Dexedrine, Dextrostat, Xelstrym, Zenzedi, others
| Drugs.com          = {{drugs.com|monograph|dextroamphetamine}}
| MedlinePlus        = a605027
| licence_EU         =
| DailyMedID         = Dextroamphetamine
| licence_US         = Dextroamphetamine
| pregnancy_AU       = B3
| pregnancy_AU_comment =
| pregnancy_category =
| dependency_liability = Moderate<ref name="Vitiello2008">{{cite journal | vauthors = Vitiello B | title = Understanding the risk of using medications for attention deficit hyperactivity disorder with respect to physical growth and cardiovascular function | journal = Child and Adolescent Psychiatric Clinics of North America | volume = 17 | issue = 2 | pages = 459–74, xi | date = April 2008 | pmid = 18295156 | pmc = 2408826 | doi = 10.1016/j.chc.2007.11.010 }}</ref><ref name="GrahamGrahamBanaschewski2010">{{cite journal | vauthors = Graham J, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Döpfner M, Hamilton R, Hollis C, Holtmann M, Hulpke-Wette M, Lecendreux M, Rosenthal E, Rothenberger A, Santosh P, Sergeant J, Simonoff E, Sonuga-Barke E, Wong IC, Zuddas A, Steinhausen HC, Taylor E | display-authors = 6 | title = European guidelines on managing adverse effects of medication for ADHD | journal = European Child & Adolescent Psychiatry | volume = 20 | issue = 1 | pages = 17–37 | date = January 2011 | pmid = 21042924 | pmc = 3012210 | doi = 10.1007/s00787-010-0140-6 | eissn = 1435-165X }}</ref> - high<ref name="KociancicReedFindling2004">{{cite journal | vauthors = Kociancic T, Reed MD, Findling RL | title = Evaluation of risks associated with short- and long-term psychostimulant therapy for treatment of ADHD in children | journal = Expert Opinion on Drug Safety | volume = 3 | issue = 2 | pages = 93–100 | date = March 2004 | pmid = 15006715 | doi = 10.1517/14740338.3.2.93 | s2cid = 31114829 | eissn = 1744-764X }}</ref><ref name="ClemowWalker2014">{{cite journal | vauthors = Clemow DB, Walker DJ | title = The potential for misuse and abuse of medications in ADHD: a review | journal = Postgraduate Medicine | volume = 126 | issue = 5 | pages = 64–81 | date = September 2014 | pmid = 25295651 | doi = 10.3810/pgm.2014.09.2801 | s2cid = 207580823 | eissn = 1941-9260 }}</ref><ref name="Stahl's Essential Psychopharmacology" />
| addiction_liability = Moderate<ref name="Vitiello2008"/><ref name="GrahamGrahamBanaschewski2010"/> - high<ref name="KociancicReedFindling2004"/><ref name="ClemowWalker2014"/><ref name="Stahl's Essential Psychopharmacology" />
| routes_of_administration = [[Medicine:Oral administration|By mouth]], [[Medicine:Transdermal patch|transdermal]]
| class              =
| ATC_prefix         = N06
| ATC_suffix         = BA02
| ATC_supplemental   = <!-- Legal status -->
| legal_AU           = S8
| legal_AU_comment   = <ref>{{cite web | title=Therapeutic Goods (Poisons Standard—February 2023) Instrument 2022 | website=Australian Government Federal Register of Legislation | url=https://www.legislation.gov.au/Series/F2022L01257 | access-date=9 January 2023}}</ref><ref>{{cite web | vauthors = Fuller K | title=ADHD Stimulant Prescribing Regulations & Authorities in Australia & New Zealand | website=AADPA | date=20 February 2022 | url=https://aadpa.com.au/adhd-stimulant-prescribing-regulations-in-australia-new-zealand/ | access-date=9 January 2023}}</ref>
| legal_BR           = A3
| legal_CA           = Schedule I
| legal_CA_comment   =
| legal_DE           = Anlage III
| legal_DE_comment   =
| legal_NZ           = <!-- Class A, B, C -->
| legal_NZ_comment   =
| legal_UK           = Class B
| legal_UK_comment   =
| legal_US           = Schedule II
| legal_US_comment   = <ref name="Dexedrine FDA label">{{cite web | title=Dexedrine spansule- dextroamphetamine sulfate capsule, extended release | website=DailyMed | date=10 January 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cc717b9b-22ea-4c60-a1d4-ee38a40bce78 | access-date=28 March 2022}}</ref><ref name="Xelstrym FDA label">{{cite web | title=Xelstrym- dextroamphetamine patch, extended release | website=DailyMed | date=6 January 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0862f02a-72a8-41cc-8845-57cf4974bb6f | access-date=21 January 2023}}</ref>
| legal_EU           = Rx-only
| legal_EU_comment   = <ref>{{cite web|url=https://www.ema.europa.eu/documents/psusa/dexamfetamine-list-nationally-authorised-medicinal-products-psusa/00000986/202109_en.pdf |title=List of nationally authorised medicinal products : Active substance(s): dexamfetamine : Procedure No. PSUSA/00000986/202109|website=Ema.europa.eu|access-date=5 June 2022}}</ref>
| legal_UN           = P II<!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment   =
| legal_status       = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->| bioavailability    = Oral: 75–100%<ref>{{cite encyclopedia| title=Dextromphetamine | url=http://www.drugbank.ca/drugs/DB01576#pharmacology | work=DrugBank | access-date=5 November 2013 | section=Pharmacology }}</ref>
| protein_bound      = 15–40%<ref name="Drugbank-amph" />
| metabolism         = [[Biology:CYP2D6|CYP2D6]],<ref name="FDA Pharmacokinetics" /> DBH,<ref name="DBH ref">{{cite book | title=Foye's Principles of Medicinal Chemistry | year=2013 | publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins | location=Philadelphia | isbn=978-1609133450 | page=648 |vauthors=Lemke TL, Williams DA, Roche VF, Zito W |edition=7th | quote=Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.}}</ref> [[Biology:Flavin-containing monooxygenase|FMO3]]<ref name="FMO" />
| metabolites        =
| onset              = {{abbr|IR|Immediate release}} dosing: 0.5–1.5&nbsp;hours<ref>{{Cite book|title = Primary Care Pediatrics|url = https://books.google.com/books?id=o43u_qWT4asC|publisher = Lippincott Williams & Wilkins|date = 1 January 2001|isbn = 9780781720083| vauthors = Green-Hernandez C, Singleton JK, Aronzon DZ |page = 243}}|quote = Table 21.2 Medications for ADHD ... D-amphetamine ... Onset: 30 min.</ref><ref>{{cite web|title = Dexedrine, ProCentra(dextroamphetamine) dosing, indications, interactions, adverse effects, and more|url = http://reference.medscape.com/drug/dexedrine-procentra-dextroamphetamine-342998#10|website = reference.medscape.com|access-date = 4 October 2015|quote = Onset of action: 1–1.5 hr}}</ref><br />{{abbr|XR|Extended release}} dosing: 1.5–2&nbsp;hours<ref name="Millichap: onset, peak, and duration">{{cite book | vauthors = Millichap JG | editor = Millichap JG | title = Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD | year = 2010 | publisher = Springer | location = New York, USA | isbn = 9781441913968 | page = 112 | edition = 2nd | chapter = Chapter 9: Medications for ADHD | quote = <br />Table 9.2 Dextroamphetamine formulations of stimulant medication<br />Dexedrine [Peak:2–3&nbsp;h] [Duration:5–6&nbsp;h]&nbsp;...<br />Adderall [Peak:2–3&nbsp;h] [Duration:5–7&nbsp;h]<br />Dexedrine spansules [Peak:7–8&nbsp;h] [Duration:12&nbsp;h]&nbsp;...<br />Adderall XR [Peak:7–8&nbsp;h] [Duration:12&nbsp;h]<br />Vyvanse [Peak:3–4&nbsp;h] [Duration:12&nbsp;h]}}</ref><ref name="XR onset-duration">{{cite journal | vauthors = Brams M, Mao AR, Doyle RL | title = Onset of efficacy of long-acting psychostimulants in pediatric attention-deficit/hyperactivity disorder | journal = Postgrad. Med. | volume = 120 | issue = 3 | pages = 69–88 | date = September 2008 | pmid = 18824827 | doi = 10.3810/pgm.2008.09.1909 | s2cid = 31791162 | quote = Onset of efficacy was earliest for d-MPH-ER at 0.5 hours, followed by d, l-MPH-LA at 1 to 2 hours, MCD at 1.5 hours, d, l-MPH-OR at 1 to 2 hours, MAS-XR at 1.5 to 2 hours, MTS at 2 hours, and LDX at approximately 2 hours.&nbsp;... MAS-XR, and LDX have a long duration of action at 12 hours postdose}}</ref>
| elimination_half-life = 9–11&nbsp;hours<ref name="FDA Pharmacokinetics" /><ref name="Adderall IR">{{cite web | title=Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet | website=DailyMed | date=27 February 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81 | access-date=21 January 2023}}</ref><br />[[Chemistry:PH|pH]]-dependent: 7–34&nbsp;hours<ref name="HSDB Toxnet October 2017 Full archived record" />
| duration_of_action = {{abbr|IR|Immediate release}} dosing: 3–6&nbsp;hours<ref name="Millichap: onset, peak, and duration" /><ref name="Narcolepsy guide">{{cite journal | vauthors = Mignot EJ | title = A practical guide to the therapy of narcolepsy and hypersomnia syndromes | journal = Neurotherapeutics | volume = 9 | issue = 4 | pages = 739–752 | date = October 2012 | pmid = 23065655 | pmc = 3480574 | doi = 10.1007/s13311-012-0150-9 }}</ref><br />{{abbr|XR|Extended release}} dosing: 8–12&nbsp;hours<ref name="Stahl's Essential Psychopharmacology - dextroamphetamine">{{cite book | vauthors=Stahl SM | title=Prescriber's Guide: Stahl's Essential Psychopharmacology | date=March 2017 | publisher=Cambridge University Press | location=Cambridge, United Kingdom | isbn=9781108228749 | pages=39–44 | edition=6th | chapter-url=https://books.google.com/books?id=9hssDwAAQBAJ&pg=PA39 | chapter=Amphetamine (D) | access-date=8 August 2017 }}</ref><ref name="Millichap: onset, peak, and duration" /><ref name="Narcolepsy guide"/>
| excretion          = Kidney (45%);<ref>{{cite web|title=dextrostat (dextroamphetamine sulfate) tablet [Shire US Inc.]|publisher=Shire US Inc.|website=DailyMed|url=http://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=1645|date=August 2006|access-date=8 November 2013|location=Wayne, PA}}</ref> urinary pH-dependent

<!-- Identifiers -->| CAS_number_Ref     = {{cascite|correct|??}}
| CAS_number         = 51-64-9
| CAS_supplemental   =
| PubChem            = 5826
| IUPHAR_ligand      = 2147
| DrugBank_Ref       = {{drugbankcite|correct|drugbank}}
| DrugBank           = DB01576
| ChemSpiderID_Ref   = {{chemspidercite|correct|chemspider}}
| ChemSpiderID       = 5621
| UNII_Ref           = {{fdacite|correct|FDA}}
| UNII               = TZ47U051FI
| KEGG_Ref           = {{keggcite|correct|kegg}}
| KEGG               = D03740
| ChEBI_Ref          = {{ebicite|correct|EBI}}
| ChEBI              = 4469
| ChEMBL_Ref         = {{ebicite|correct|EBI}}
| ChEMBL             = 612
| NIAID_ChemDB       =
| PDB_ligand         =
| synonyms           = d-Amphetamine, (S)-Amphetamine, S(+)-Amphetamine

<!-- Chemical and physical data -->| IUPAC_name         = (2''S'')-1-Phenylpropan-2-amine
| C                  = 9
| H                  = 13
| N                  = 1
| SMILES             = C[C@@H](Cc1ccccc1)N
| StdInChI_Ref       = {{stdinchicite|changed|chemspider}}
| StdInChI           = InChI=1S/C9H13N/c1-8(10)7-9-5-3-2-4-6-9/h2-6,8H,7,10H2,1H3/t8-/m0/s1
| StdInChI_comment   =
| StdInChIKey_Ref    = {{stdinchicite|correct|chemspider}}
| StdInChIKey        = KWTSXDURSIMDCE-QMMMGPOBSA-N
| density            = 0.913
| density_notes      =
| melting_point      =
| melting_high       =
| melting_notes      =
| boiling_point      = 201.5
| boiling_notes      =
| solubility         = 20
| sol_units          =
| specific_rotation  =
}}

'''Dextroamphetamine''' is a potent [[Biology:Central nervous system|central nervous system]] (CNS) [[Chemistry:Stimulant|stimulant]] and [[Chemistry:Enantiomer|enantiomer]]<ref name="Enantiomer" group="note" /> of [[Chemistry:Amphetamine|amphetamine]] that is prescribed for the treatment of [[Medicine:Attention deficit hyperactivity disorder|attention deficit hyperactivity disorder]] (ADHD) and [[Medicine:Narcolepsy|narcolepsy]].<ref name="Dexedrine FDA label" /><ref name="Amph Uses" /> It is also used as an athletic performance and [[Chemistry:Nootropic|cognitive enhancer]], and recreationally as an aphrodisiac and [[Chemistry:Euphoriant|euphoriant]].

The amphetamine molecule exists as two enantiomers,{{#tag:ref|Enantiomers are molecules that are mirror images of one another; they are structurally identical, but of the opposite orientation.<ref name="Enantiomers">{{GoldBookRef |title=enantiomer |file=E02069 }}</ref>|group = "note" |name="Enantiomer"}} [[Chemistry:Levoamphetamine|levoamphetamine]] and dextroamphetamine. Dextroamphetamine is the dextrorotatory, or 'right-handed', enantiomer and exhibits more pronounced effects on the central nervous system than levoamphetamine. Pharmaceutical dextroamphetamine sulfate is available as both a brand name and [[Social:Generic drug|generic drug]] in a variety of [[Medicine:Dosage form|dosage form]]s. Dextroamphetamine is sometimes prescribed as the inactive prodrug lisdexamfetamine dimesylate, which is converted into dextroamphetamine after absorption.

Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or [[Biology:Reverse transport|reverses the transporter proteins]] for the monoamine neurotransmitters (namely the [[Biology:Serotonin transporter|serotonin]], [[Biology:Norepinephrine transporter|norepinephrine]] and [[Biology:Dopamine transporter|dopamine transporter]]s) either via trace amine-associated receptor 1 (TAAR1) or in a TAAR1 independent fashion when there are high cytosolic concentrations of the monoamine neurotransmitters<ref name=Miller/> and it releases these neurotransmitters from synaptic vesicles via [[Biology:Vesicular monoamine transporter 2|vesicular monoamine transporter 2]].<ref name="E Weihe" /> It also shares many chemical and pharmacological properties with human [[Biology:Trace amine|trace amine]]s, particularly [[Biology:Phenethylamine|phenethylamine]] and {{nowrap|''N''-methylphenethylamine}}, the latter being an [[Chemistry:Isomer|isomer]] of amphetamine produced within the human body.

==Uses==

===Medical===
{{transcluded section|source=Amphetamine|part=yes}}
[[File:Dextroamphetamine.jpg|thumb|250px|Dextroamphetamine 5mg tablets]]
[[File:Dexedrine doj2.jpeg|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 [[Medicine:Narcolepsy|narcolepsy]] (a sleep disorder),<ref name="Dexedrine FDA label" /> and is sometimes prescribed {{nowrap|off-label}} for depression and obesity.<ref name="Amph Uses" />
{{trim|{{#section-h:Amphetamine|Medical}}}}

===Enhancing performance===
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Enhancing performance}}}}

===Recreational===
Dextroamphetamine is also used recreationally as a euphoriant and aphrodisiac, and like other amphetamines is used as a [[Chemistry:Club drug|club drug]] for its energetic and euphoric high. Dextroamphetamine is considered to have a high potential for misuse in a recreational manner since individuals typically report feeling [[Chemistry:Euphoria|euphoric]], more alert, and more energetic after taking the drug.<ref>{{cite web|url=http://www.drugabuse.gov/drugs-abuse/commonly-abused-drugs/commonly-abused-prescription-drugs-chart |title=Commonly Abused Prescription Drugs Chart |publisher=National Institute on Drug Abuse|access-date=7 May 2012}}</ref><ref>{{cite web |url=http://www.drugabuse.gov/publications/infofacts/stimulant-adhd-medications-methylphenidate-amphetamines |title=Stimulant ADHD Medications – Methylphenidate and Amphetamines |publisher=National Institute on Drug Abuse |access-date=7 May 2012 |archive-date=2 May 2012 |archive-url=https://web.archive.org/web/20120502072325/http://www.drugabuse.gov/publications/infofacts/stimulant-adhd-medications-methylphenidate-amphetamines |url-status=dead }}</ref><ref name="NIDA ADHD stimulants" /> Dextroamphetamine's [[Chemistry:Dopaminergic|dopaminergic]] (rewarding) properties affect the mesocorticolimbic circuit; a group of neural structures responsible for incentive salience (i.e., "wanting"; desire or craving for a reward and motivation), positive reinforcement and positively-valenced emotions, particularly ones involving [[Philosophy:Pleasure|pleasure]].<ref name=Schultz>{{cite journal | vauthors = Schultz W | year = 2015 | title = Neuronal reward and decision signals: from theories to data | journal = Physiological Reviews | volume = 95 | issue = 3 | pages = 853–951 | pmid = 26109341 | pmc = 4491543 | doi=10.1152/physrev.00023.2014 | quote = Rewards in operant conditioning are positive reinforcers.&nbsp;...  Operant behavior gives a good definition for rewards. Anything that makes an individual come back for more is a positive reinforcer and therefore a reward. Although it provides a good definition, positive reinforcement is only one of several reward functions.&nbsp;... Rewards are attractive. They are motivating and make us exert an effort.&nbsp;... Rewards induce approach behavior, also called appetitive or preparatory behavior, sexual behavior, and consummatory behavior.&nbsp;... Thus any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward.&nbsp;... Rewarding stimuli, objects, events, situations, and activities consist of several major components. First, rewards have basic sensory components (visual, auditory, somatosensory, gustatory, and olfactory)&nbsp;... Second, rewards are salient and thus elicit attention, which are manifested as orienting responses. The salience of rewards derives from three principal factors, namely, their physical intensity and impact (physical salience), their novelty and surprise (novelty/surprise salience), and their general motivational impact shared with punishers (motivational salience). A separate form not included in this scheme, incentive salience, primarily addresses dopamine function in addiction and refers only to approach behavior (as opposed to learning)&nbsp;... Third, rewards have a value component that determines the positively motivating effects of rewards and is not contained in, nor explained by, the sensory and attentional components. This component reflects behavioral preferences and thus is subjective and only partially determined by physical parameters. Only this component constitutes what we understand as a reward. It mediates the specific behavioral reinforcing, approach generating, and emotional effects of rewards that are crucial for the organism's survival and reproduction, whereas all other components are only supportive of these functions.&nbsp;... Rewards can also be intrinsic to behavior. They contrast with extrinsic rewards that provide motivation for behavior and constitute the essence of operant behavior in laboratory tests. Intrinsic rewards are activities that are pleasurable on their own and are undertaken for their own sake, without being the means for getting extrinsic rewards.&nbsp;... Intrinsic rewards are genuine rewards in their own right, as they induce learning, approach, and pleasure, like perfectioning, playing, and enjoying the piano. Although they can serve to condition higher order rewards, they are not conditioned, higher order rewards, as attaining their reward properties does not require pairing with an unconditioned reward.&nbsp;...  These emotions are also called liking (for pleasure) and wanting (for desire) in addiction research and strongly support the learning and approach generating functions of reward.}}</ref>  Large recreational doses of dextroamphetamine may produce symptoms of dextroamphetamine overdose.<ref name="NIDA ADHD stimulants" /> Recreational users sometimes open dexedrine capsules and crush the contents in order to insufflate (snort) it or subsequently dissolve it in water and inject it.<ref name="NIDA ADHD stimulants">{{cite web|title=National Institute on Drug Abuse. 2009. Stimulant ADHD Medications – Methylphenidate and Amphetamines|url=http://www.drugabuse.gov/publications/drugfacts/stimulant-adhd-medications-methylphenidate-amphetamines|publisher=National Institute on Drug Abuse|access-date=27 February 2013}}</ref> 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).<ref name="CADDRA_2018">{{cite book |title=Canadian ADHD Practice Guidelines |date=2018 |publisher=Canadian ADHD Resource Alliance |page=67 |edition=Fourth |url=https://www.caddra.ca/wp-content/uploads/CADDRA-Guidelines-4th-Edition_-Feb2018.pdf |access-date=2 May 2023 |archive-date=2 May 2023 |archive-url=https://web.archive.org/web/20230502204112/https://www.caddra.ca/wp-content/uploads/CADDRA-Guidelines-4th-Edition_-Feb2018.pdf |url-status=dead }}</ref><ref name="Bright2008">{{cite journal | vauthors = Bright GM | title = Abuse of medications employed for the treatment of ADHD: results from a large-scale community survey | journal = Medscape Journal of Medicine | volume = 10 | issue = 5 | pages = 111 | date = May 2008 | pmid = 18596945 | pmc = 2438483 }}</ref>

The reason for using crushed spansules for insufflation and injection [[Medicine:Route of administration|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.<ref name="Contextual conditioning">{{cite journal | vauthors = Childs E, de Wit H | title = Contextual conditioning enhances the psychostimulant and incentive properties of d-amphetamine in humans | journal = Addict Biology | date = November 2013 | volume = 18 | issue = 6 | pages = 985–992 | pmid = 22129527 | pmc = 4242554 | doi = 10.1111/j.1369-1600.2011.00416.x }}</ref> Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.<ref name="NIDA ADHD stimulants" /> Chronic overuse of dextroamphetamine can lead to severe drug dependence, resulting in withdrawal symptoms when drug use stops.<ref name="NIDA ADHD stimulants" />

==Contraindications==
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Contraindications}}}}

==Adverse effects==
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Adverse effects}}}}

==Overdose==
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Overdose}}}}

==Interactions==
Many types of substances are known to [[Medicine:Drug interaction|interact]] with amphetamine, resulting in altered [[Chemistry:Drug action|drug action]] or [[Biology:Drug metabolism|metabolism]] of amphetamine, the interacting substance, or both.<ref name="FDA Pharmacokinetics" /><ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Inhibitors of the enzymes that metabolize amphetamine (e.g., CYP2D6 and [[Biology:Flavin-containing monooxygenase 3#Ligands|FMO3]]) will prolong its elimination half-life, meaning that its effects will last longer.<ref name="FMO" /><ref name="Adderall FDA label">{{cite web | title=Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet | website=DailyMed | date=27 February 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f22635fe-821d-4cde-aa12-419f8b53db81 | access-date=28 March 2022}}</ref><ref name="Adderall XR FDA label">{{cite web | title=Adderall XR- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate capsule, extended release | website=DailyMed | date=3 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aff45863-ffe1-4d4f-8acf-c7081512a6c0 | access-date=28 March 2022}}</ref> Amphetamine also interacts with {{abbr|MAOIs|monoamine oxidase inhibitors}}, particularly [[Biology:Monoamine oxidase A|monoamine oxidase A]] inhibitors, since both MAOIs and amphetamine increase [[Biology:Blood plasma|plasma]] catecholamines (i.e., norepinephrine and dopamine);<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> therefore, concurrent use of both is dangerous.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of [[Chemistry:Sedative|sedative]]s and depressants and increase the effects of [[Chemistry:Stimulant|stimulant]]s and [[Chemistry:Antidepressant|antidepressant]]s.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Amphetamine may also decrease the effects of antihypertensives and [[Chemistry:Antipsychotic|antipsychotic]]s due to its effects on blood pressure and dopamine respectively.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Zinc supplementation may reduce the minimum [[Medicine:Effective dose (pharmacology)|effective dose]] of amphetamine when it is used for the treatment of ADHD.{{#tag:ref|The human [[Biology:Dopamine transporter|dopamine transporter]] contains a high affinity extracellular zinc [[Biology:Binding site|binding site]] which, upon zinc binding, inhibits dopamine [[Biology:Reuptake|reuptake]] and amplifies amphetamine-induced dopamine efflux ''[[In vitro|in vitro]]''.<ref name="Zinc binding sites + ADHD review">{{cite journal | vauthors = Krause J | title = SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder | journal = Expert Rev. Neurother. | volume = 8 | issue = 4 | pages = 611–625 | date = April 2008 | pmid = 18416663 | doi = 10.1586/14737175.8.4.611 | s2cid = 24589993 | quote = Zinc binds at&nbsp;... extracellular sites of the DAT [103], serving as a DAT inhibitor. In this context, controlled double-blind studies in children are of interest, which showed positive effects of zinc [supplementation] on symptoms of ADHD [105,106]. It should be stated that at this time [supplementation] with zinc is not integrated in any ADHD treatment algorithm.}}</ref><ref name="Review - cites 2002 amph-zinc primary study">{{cite journal | vauthors = Sulzer D | title = How addictive drugs disrupt presynaptic dopamine neurotransmission | journal = Neuron | volume = 69 | issue = 4 | pages = 628–649 | date = February 2011 | pmid = 21338876 | pmc = 3065181 | doi = 10.1016/j.neuron.2011.02.010 | quote = They did not confirm the predicted straightforward relationship between uptake and release, but rather that some compounds including AMPH were better releasers than substrates for uptake. Zinc, moreover, stimulates efflux of intracellular [3H]DA despite its concomitant inhibition of uptake (Scholze et al., 2002).}}</ref><ref name="Primary 2002 amph-zinc study">{{cite journal | vauthors = Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH | title = The role of zinc ions in reverse transport mediated by monoamine transporters | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 21505–21513 | date = June 2002 | pmid = 11940571 | doi = 10.1074/jbc.M112265200| doi-access =  free}}</ref> The human [[Biology:Serotonin transporter|serotonin transporter]] and [[Biology:Norepinephrine transporter|norepinephrine transporter]] do not contain zinc binding sites.<ref name="Primary 2002 amph-zinc study" />|group="note"}}<ref name="Zinc and PEA">{{cite journal |vauthors=Scassellati C, Bonvicini C, Faraone SV, Gennarelli M | title = Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses | journal = J. Am. Acad. Child Adolesc. Psychiatry | volume = 51 | issue = 10 | pages = 1003–1019.e20 | date = October 2012 | pmid = 23021477 | doi = 10.1016/j.jaac.2012.08.015}}</ref>

==Pharmacology==

===Pharmacodynamics===
{{hatnote|Main section: {{section link|Amphetamine|Pharmacodynamics}}}}
{{Amphetamine pharmacodynamics}}
Amphetamine and its enantiomers have been identified as potent full agonists of [[Biology:TAAR1|trace amine-associated receptor 1]] (TAAR1), a [[Biology:G protein-coupled receptor|GPCR]], discovered in 2001, that is important for regulation of [[Biology:Monoaminergic|monoaminergic]] systems in the brain.<ref name="pmid11723224">{{cite journal | vauthors = 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 | display-authors = 6 | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Molecular Pharmacology | volume = 60 | issue = 6 | pages = 1181–1188 | date = December 2001 | pmid = 11723224 | doi = 10.1124/mol.60.6.1181 | s2cid = 14140873 }}</ref><ref name="TAAR1 stereoselective" /> Activation of TAAR1 increases [[Chemistry:Cyclic adenosine monophosphate|cAMP]] production via [[Biology:Adenylyl cyclase|adenylyl cyclase]] activation and inhibits the function of the [[Biology:Dopamine transporter|dopamine transporter]], [[Biology:Norepinephrine transporter|norepinephrine transporter]], and [[Biology:Serotonin transporter|serotonin transporter]], as well as inducing the release of these monoamine neurotransmitters (effluxion).<ref name="Miller">{{cite journal | vauthors = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = Journal of Neurochemistry | volume = 116 | issue = 2 | pages = 164–176 | date = January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="pmid11723224" /><ref name="pmid11459929">{{cite journal | vauthors = 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 | display-authors = 6 | title = Trace amines: identification of a family of mammalian G protein-coupled receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 16 | pages = 8966–8971 | date = July 2001 | pmid = 11459929 | pmc = 55357 | doi = 10.1073/pnas.151105198 | doi-access = free | bibcode = 2001PNAS...98.8966B }}</ref> Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called VMAT2.<ref name="E Weihe" /> When amphetamine is taken up by VMAT2, the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.<ref name="E Weihe">{{cite journal | vauthors = Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Annals of the New York Academy of Sciences | volume = 1216 | issue = 1 | pages = 86–98 | date = January 2011 | pmid = 21272013 | pmc = 4183197 | doi = 10.1111/j.1749-6632.2010.05906.x | bibcode = 2011NYASA1216...86E }}</ref>

Dextroamphetamine (the dextrorotary [[Chemistry:Enantiomer|enantiomer]]) and [[Chemistry:Levoamphetamine|levoamphetamine]] (the levorotary enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary.<ref name="TAAR1 stereoselective" /><ref name="WestfallDP">{{cite book |veditors=Brunton LL, Chabner BA, Knollmann BC | title = Goodman & Gilman's Pharmacological Basis of Therapeutics | year = 2010 | publisher = McGraw-Hill | location = New York | isbn = 9780071624428 |vauthors=Westfall DP, Westfall TC | section = Miscellaneous Sympathomimetic Agonists | section-url = http://www.accessmedicine.com/content.aspx?aID=16661601 | edition = 12th }}</ref> Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine.<ref name="TAAR1 stereoselective" /> Consequently, dextroamphetamine produces roughly three to four times more [[Biology:Central nervous system|central nervous system]] (CNS) stimulation than levoamphetamine;<ref name="TAAR1 stereoselective">{{cite journal |vauthors=Lewin AH, Miller GM, Gilmour B | title = Trace amine-associated receptor 1 is a stereoselective binding site for compounds in the amphetamine class | journal = Bioorg. Med. Chem. | volume = 19 | issue = 23 | pages = 7044–7048 | date = December 2011 | pmid = 22037049 | pmc = 3236098 | doi = 10.1016/j.bmc.2011.10.007 }}</ref><ref name="WestfallDP" /> however, levoamphetamine has slightly greater cardiovascular and peripheral effects.<ref name="WestfallDP" />

===Related endogenous compounds===
{{trim|{{#section-h:Amphetamine|Related endogenous compounds}}}}

===Pharmacokinetics===
{{transcluded section|source=Amphetamine}}
{{trim|{{#section-h:Amphetamine|Pharmacokinetics}}}}
{{clear}}

==History, society, and culture==
Racemic amphetamine was first [[Chemistry:Chemical synthesis|synthesized]] under the chemical name "phenylisopropylamine" in [[Place:Berlin|Berlin]], 1887 by the Romanian chemist Lazăr Edeleanu. It was not widely marketed until 1932, when the pharmaceutical company Smith, Kline & French (now known as [[Company:GlaxoSmithKline|GlaxoSmithKline]]) introduced it in the form of the Benzedrine inhaler for use as a [[Medicine:Bronchodilator|bronchodilator]]. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base,<ref group="note">Free-base form amphetamine is a volatile oil, hence the efficacy of the inhalers.</ref> not a chloride or sulfate salt.

Three years later, 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.<ref>{{cite web|title=Dexedrine|url=http://www.medic8.com/medicines/Dexedrine.html|website=Medic8|access-date=27 November 2013|url-status=dead|archive-url=https://web.archive.org/web/20091219120223/http://www.medic8.com/medicines/Dexedrine.html|archive-date=19 December 2009}}</ref> In the United States, Dexedrine was approved to treat [[Medicine:Narcolepsy|narcolepsy]] and attention disorders.<ref name="Dexedrine FDA label" /> In Canada [[Medicine:Indication|indication]]s once included epilepsy and parkinsonism.<ref>{{cite web| url =http://www.mentalhealth.com/drug/p30-d04.html| title =Dextroamphetamine [monograph]| website =Internet Mental Health| archive-url =https://web.archive.org/web/20060427084347/http://www.mentalhealth.com/drug/p30-d04.html| access-date =6 September 2015| archive-date=27 April 2006}}</ref> 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 [[Chemistry:Amobarbital|amobarbital]] (a [[Chemistry:Barbiturate|barbiturate]]) sold under the tradename [[Chemistry:Dexamyl|Dexamyl]] and, in the 1950s, an extended release capsule (the "Spansule").<ref>{{cite web|url=http://www.weitzlux.com/Dexedrine/information_403484.html |title=Information on Dexedrine: A Quick Review {{pipe}} Weitz & Luxenberg |publisher=Weitzlux.com |date=31 August 2013 |access-date=5 January 2017}}</ref> Preparations containing dextroamphetamine were also used in [[Social:World War II|World War II]] as a treatment against fatigue.<ref name = nutt>{{cite journal |vauthors=Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present—a pharmacological and clinical perspective | journal = Journal of Psychopharmacology | volume = 27 | issue = 6 | pages = 479–96 | date = June 2013 | pmid = 23539642 | doi = 10.1177/0269881113482532 | pmc = 3666194 }}</ref>

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.<ref>{{cite web | vauthors = King DG | date = 4 January 2017 | url = http://www.denton.handwritingexperts.com/articles/prescriptionforgery1.html | title = Prescription Forgery | work = Handwriting Services International | archive-url = https://web.archive.org/web/20080705185842/http://www.denton.handwritingexperts.com/articles/prescriptionforgery1.html | archive-date = 5 July 2008 }}</ref> 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).<ref name="pharaman">{{cite book | url = http://www.knovel.com/web/portal/browse/display?_EXT_KNOVEL_DISPLAY_bookid=598 | title = Pharmaceutical Manufacturing Encyclopedia | edition = 2nd | veditors = Sittig M | volume = 1 | publisher = Noyes Publications | isbn = 978-0-8155-1144-1}}</ref> It became popular on the [[Philosophy:Mod (subculture)|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, [[Company:GlaxoSmithKline|GlaxoSmithKline]] sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).<ref>{{cite web|title=Dexedrine FAQs|url=http://www.dexedrine.net/faq.asp|url-status=dead|archive-url=https://web.archive.org/web/20110617013326/http://www.dexedrine.net/faq.asp|archive-date=17 June 2011}}</ref>

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".<ref name = "Bonné_2003">{{cite web | vauthors =  Bonné J |url=http://www.nbcnews.com/id/3071789/ns/us_news-only/t/go-pills-war-drugs/ |title='Go pills': A war on drugs? |work=NBC News |date=9 January 2003 |access-date=5 January 2017}}</ref><ref name=airforcegopills>{{cite web | vauthors = Woodring JC |url=http://www.af.mil/news/story.asp?id=123007615 |title=Air Force scientists battle aviator fatigue |access-date=5 January 2017 |url-status= dead |archive-url=https://web.archive.org/web/20121014113247/http://www.af.mil/news/story.asp?id=123007615 |archive-date=14 October 2012 }}</ref><ref>{{cite journal |vauthors=Emonson DL, Vanderbeek RD | title = The use of amphetamines in U.S. Air Force tactical operations during Desert Shield and Storm | journal = Aviation, Space, and Environmental Medicine | volume = 66 | issue = 3 | pages = 260–3 | year = 1995 | pmid = 7661838 }}</ref> 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 [[Chemistry:Stimulant|stimulant]] medications or awakeness promoting agents with different side effect profiles, such as [[Chemistry:Modafinil|modafinil]], are being investigated and sometimes issued for this reason.<ref name=airforcegopills />

===Formulations===

{| class="wikitable sortable" style="text-align:center;"
|+ Dextroamphetamine pharmaceuticals and prodrugs{{#tag:ref|These represent the current brands in the United States, except Dexedrine instant release tablets. Dexedrine tablets, introduced in 1937, is discontinued but available as Zenzedi and generically;<ref>{{cite journal | vauthors = Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present--a pharmacological and clinical perspective | journal = Journal of Psychopharmacology | volume = 27 | issue = 6 | pages = 479–496 | date = June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532 | quote = Smith, Kline and French synthesised both isomers, and in 1937 commenced marketing of d-amphetamine, which was the more potent of the two isomers, under the trade name of Dexedrine. }}</ref><ref>{{cite web | title=Drugs@FDA: Dexedrine | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=BasicSearch.process | access-date=28 March 2022}}</ref> Dexedrine listed here represents the extended release "Spansule" capsule which was approved in 1976.<ref>{{cite web | title=Drugs@FDA: Dexedrine | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=017078 | access-date=28 March 2022}}</ref><ref>{{cite web|title = Drugs@FDA: Dexedrine: Label and Approval History|url = http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Set_Current_Drug&ApplNo=017078&DrugName=DEXEDRINE&ActiveIngred=DEXTROAMPHETAMINE%2520SULFATE&SponsorApplicant=AMEDRA%2520PHARMS&ProductMktStatus=1&goto=Search.Label_ApprovalHistory|website = U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|access-date = 30 December 2015|quote = 08/02/1976 ... Approval|archive-date = 28 August 2021|archive-url = https://web.archive.org/web/20210828060742/https://www.accessdata.fda.gov/scripts/cder/daf/|url-status = dead}}</ref> Amphetamine sulfate tablets, now sold as Evekeo (brand), were originally sold as Benzedrine (brand) sulfate in 1935<ref>{{cite journal | vauthors = Strohl MP | title = Bradley's Benzedrine studies on children with behavioral disorders | journal = The Yale Journal of Biology and Medicine | volume = 84 | issue = 1 | pages = 27–33 | date = March 2011 | pmid = 21451781 | pmc = 3064242 | quote = Bradley experimented with Benzedrine sulfate, a drug marketed to doctors by the company Smith, Kline & French (SKF) between 1935 and 1937... }}</ref><ref>{{cite journal | vauthors = Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present--a pharmacological and clinical perspective | journal = Journal of Psychopharmacology | volume = 27 | issue = 6 | pages = 479–496 | date = June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532 | quote = Smith, Kline and French introduced Benzedrine onto the market in 1935 as a treatment for narcolepsy (for which it is still used today), mild depression, post-encephalitic Parkinsonism and a raft of other disorders. }}</ref> and discontinued sometime after 1982.<ref>{{cite journal | vauthors = Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present--a pharmacological and clinical perspective | journal = Journal of Psychopharmacology | volume = 27 | issue = 6 | pages = 479–496 | date = June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532 | quote = The use of Benzedrine to treat ADHD declined dramatically after Gross (1976) reported that the racemate was significantly less clinically effective than Dexedrine. Currently, the only use of l-amphetamine in ADHD medications is in mixed salts/mixed enantiomers amphetamine... }}</ref><ref>{{cite web|url = http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist|title = FDA Approved Drug Products: Label and Approval History (Benzedrine)|website = U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA)|access-date = 11 March 2016|quote = Action Date 5/11/1982, Supplement Number 007, Approval Type Chemistry}}</ref>| group = "note" }}
! scope="col" | Brand<br />name
! scope="col" | United States<br />Adopted Name
! scope="col" class="unsortable" style="text-align:center" | (D:L)&nbsp;ratio
! scope="col"| Dosage<br />form
! scope="col" class="unsortable" | Marketing<br />start&nbsp;date
! scope="col" class="unsortable" | <small>Sources</small>
|-
| Adderall || Mixed amphetamine salts || 3:1&nbsp;<small>(salts)</small><!-- DO NOT CHANGE THIS RATIO: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666194/table/table1-0269881113482532/ -->|| tablet || 1996 || <ref name="Amph Uses" /><ref name="NDCD" />
|-
| Adderall&nbsp;XR || Mixed amphetamine salts || 3:1&nbsp;<small>(salts)</small> || capsule || 2001 || <ref name="Amph Uses">{{cite journal |vauthors=Heal DJ, Smith SL, Gosden J, Nutt DJ | title = Amphetamine, past and present – a pharmacological and clinical perspective | journal = J. Psychopharmacol. | volume = 27 | issue = 6 | pages = 479–496 |date=June 2013 | pmid = 23539642 | pmc = 3666194 | doi = 10.1177/0269881113482532}}</ref><ref name="NDCD">{{cite web | title = National Drug Code Amphetamine Search Results | url = http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | website = National Drug Code Directory|publisher=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | access-date = 16 December 2013 | archive-url = https://web.archive.org/web/20131216080856/http://www.accessdata.fda.gov/scripts/cder/ndc/results.cfm?beginrow=1&numberperpage=160&searchfield=amphetamine&searchtype=ActiveIngredient&OrderBy=ProprietaryName | archive-date=16 December 2013}}</ref>
|-
| Mydayis || Mixed amphetamine salts || 3:1&nbsp;<small>(salts)</small> || capsule || 2017 || <ref name="Mydayis">{{cite web | title=Mydayis- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate capsule, extended release | website=DailyMed | date=28 October 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=141a7970-3f06-44ea-9ab7-aeece2c085fc | access-date=21 January 2023}}</ref>
|-
| Adzenys XR-ODT || amphetamine || 3:1&nbsp;<small>(base)</small> || [[Medicine:Orally disintegrating tablet|ODT]] || 2016 || <ref name="Adzenys">{{cite web | title=Adzenys XR-ODT- amphetamine tablet, orally disintegrating | website=DailyMed | date=10 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c1179269-00b5-48ea-972d-31e614e99b7e | access-date=21 January 2023}}</ref><ref name="FDA Adzenys approval date">{{cite web | title=Drug Approval Package: Adzenys XR-ODT (amphetamine) | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | date=27 January 2016 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/204326Orig1_toc.cfm | access-date=21 January 2023}}</ref>
|-
| Dyanavel&nbsp;XR || amphetamine ||3.2:1&nbsp;<small>(base)</small> ||suspension || 2015 || <ref name="Dyanavel" /><ref name="FDA Dyanavel approval date">{{cite web | title=Drug Approval Package: Dyanavel XR | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | date=21 March 2022 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2022/210526Orig1s000TOC.cfm | access-date=21 January 2023}}</ref>
|-
| Evekeo || amphetamine sulfate || 1:1&nbsp;<small>(salts)</small> || tablet || 2012 || <ref name="Evekeo"/><!-- defined by transclusion from Amphetamine|Contraindications --> <ref name="Racemic amph - FDA Evekeo status">{{cite web | title=Evekeo | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=200166 | website=U.S. [[Organization:Food and Drug Administration|Food and Drug Administration]] (FDA) | access-date=11 August 2015}}</ref>
|-
| Dexedrine || dextroamphetamine&nbsp;sulfate || 1:0&nbsp;<small>(salts)</small> || capsule || 1976 || <ref name="Amph Uses" /><ref name="NDCD" />
|-
| Zenzedi || dextroamphetamine&nbsp;sulfate || 1:0&nbsp;<small>(salts)</small> || tablet || 2013 || <ref name="NDCD" />
|-
| rowspan=2 | Vyvanse || rowspan=2 | lisdexamfetamine&nbsp;dimesylate || rowspan=2 | 1:0&nbsp;<small>(prodrug)</small> || capsule || rowspan=2 | 2007 || rowspan=2 | <ref name="Amph Uses" /><ref name=USVyvanselabel />
|-
| tablet
|-
| Xelstrym || dextroamphetamine || 1:0&nbsp;<small>(base)</small> || patch || 2022 || <ref name="Xelstrym FDA label" />
|}

==== Transdermal Dextroamphetamine Patches ====
Dextroamphetamine is available as a [[Medicine:Transdermal patch|transdermal patch]] containing dextroamphetamine base under the brand name Xelstrym.<ref name="Xelstrym FDA label" />

==== Dextroamphetamine sulfate ====
[[File:Dextroamphetamine.jpg|thumb|Dexamphetamine 5 mg generic name tablets]]

In the United States, immediate release (IR) formulations of dextroamphetamine [[Chemistry:Sulfate|sulfate]] are available generically as 5&nbsp;mg and 10&nbsp;mg tablets, marketed by Barr ([[Company:Teva Pharmaceutical Industries|Teva Pharmaceutical Industries]]), [[Company:Mallinckrodt|Mallinckrodt Pharmaceuticals]], Wilshire Pharmaceuticals, Aurobindo Pharmaceutical USA and CorePharma. Previous IR tablets sold under the brand names Dexedrine and Dextrostat have been discontinued but in 2015, IR tablets became available by the brand name Zenzedi, offered as 2.5&nbsp;mg, 5&nbsp;mg, 7.5&nbsp;mg, 10&nbsp;mg, 15&nbsp;mg, 20&nbsp;mg and 30&nbsp;mg tablets.<ref>{{cite web|url=http://zenzedi.com/ |title=Zenzedi (dextroamphetamine sulfate, USP) |publisher=Zenzedi.com |access-date=5 January 2017}}</ref> Dextroamphetamine sulfate is also available as a controlled-release (CR) capsule preparation in strengths of 5&nbsp;mg, 10&nbsp;mg, and 15&nbsp;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&nbsp;mg dextroamphetamine.<ref>{{cite web | url = http://www.fsclabs.com/ProCentra.html | title = ProCentra (dextroamphetamine sulfate 5 mg/5 mL Oral Solution) | work = FSC Laboratories | archive-url = https://web.archive.org/web/20101005052859/http://www.fsclabs.com/ProCentra.html | archive-date = 5 October 2010 }}</ref> The conversion rate between dextroamphetamine sulfate to amphetamine free base is .728.<ref>{{cite patent | inventor = Mickle T, Krishnan S, Bishop B, Lauderback C, Moncrief JS, Oberlender R, Piccariello T, Paul BJ, Verbicky CD | gdate = 2010 | title = Abuse-resistant amphetamine prodrugs | country = US | number = 7655630 | assign1 = Takeda Pharmaceutical Co Ltd }}</ref>

In Australia, dexamfetamine is available in bottles of 100 instant release 5&nbsp;mg tablets as a [[Social:Generic drug|generic drug]]<ref>{{cite journal|doi=10.18773/austprescr.1995.064 |title=Stimulant treatment for attention deficit hyperactivity disorder |journal=Australian Prescriber |volume=18 |issue=3 |pages=60–63 |year=1995 | vauthors = Hazell P |doi-access= }}</ref> or slow release dextroamphetamine preparations may be compounded by individual chemists.<ref>{{cite web |url=http://www0.health.nsw.gov.au/PublicHealth/Pharmaceutical/adhd/faqs.asp |title=Pharmaceutical Services |publisher=.health.nsw.gov.au |access-date=5 January 2017 |url-status=dead |archive-url=https://web.archive.org/web/20130505045845/http://www0.health.nsw.gov.au/PublicHealth/Pharmaceutical/adhd/faqs.asp |archive-date=5 May 2013 }}</ref> In the United Kingdom, it is available in 5&nbsp;mg instant release sulfate tablets under the generic name dexamfetamine sulfate as well as 10&nbsp;mg and 20&nbsp;mg strength tablets under the brand name Amfexa. It is also available in generic dexamfetamine sulfate 5&nbsp;mg/ml oral sugar-free syrup.<ref>{{cite web |title=Dexamfetamine sulphate - Medicinal forms |url=https://bnf.nice.org.uk/medicinal-forms/dexamfetamine-sulfate.html |website=British National Formulary |publisher=BMJ Group and Pharmaceutical Press (Royal Pharmaceutical Society) |access-date=9 November 2019}}</ref> 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).<ref>{{cite journal | title = Dexamfetamine – Prescribe Generically | url = http://www.ipnsm.hscni.net/news/RedAmberNewsNov10.pdf | journal = Red/Amber News | issue = 22 | archive-url = https://web.archive.org/web/20130518094535/http://www.ipnsm.hscni.net/news/RedAmberNewsNov10.pdf | archive-date=18 May 2013 | page = 2 | publisher = Interface Pharmacist Network Specialist Medicines (IPNSM) | date = November 2010 | access-date = 20 April 2012 }}</ref>

==== Lisdexamfetamine ====
{{Main|Chemistry:Lisdexamfetamine}}
Dextroamphetamine is the active [[Biology:Metabolite|metabolite]] of the [[Chemistry:Prodrug|prodrug]] lisdexamfetamine (L-lysine-dextroamphetamine), available by the brand name Vyvanse (Elvanse in the European market) (Venvanse in the Brazil market) (lisdexamfetamine di[[Chemistry:Mesylate|mesylate]]). 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.<ref>{{cite journal | vauthors = Hutson PH, Pennick M, Secker R | title = Preclinical pharmacokinetics, pharmacology and toxicology of lisdexamfetamine: a novel d-amphetamine pro-drug | journal = Neuropharmacology | volume = 87 | pages = 41–50 | date = December 2014 | pmid = 24594478 | doi = 10.1016/j.neuropharm.2014.02.014 | s2cid = 37893582 }}</ref><ref>{{cite web | vauthors = Elayan I | url = https://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/021977s000_PharmToxR.pdf | title = NRP-104 (lisdexamphetamine dimesylate) | work = Pharmacology/Toxicology Review and Evaluation | publisher = U.S. Food and Drug Administration | date = 2006 | pages = 18–19 }}</ref> Vyvanse is marketed as once-a-day dosing as it provides a slow release of dextroamphetamine into the body. Vyvanse is available as [[Medicine:Capsule (pharmacy)|capsules]], and chewable tablets, and in seven strengths; 10&nbsp;mg, 20&nbsp;mg, 30&nbsp;mg, 40&nbsp;mg, 50&nbsp;mg, 60&nbsp;mg, and 70&nbsp;mg. The conversion rate between lisdexamfetamine dimesylate (Vyvanse) to dextroamphetamine base is 29.5%.<ref>{{cite journal | vauthors = Mohammadi M, Akhondzadeh S | title = Advances and considerations in attention-deficit/hyperactivity disorder pharmacotherapy | journal = Acta Medica Iranica | volume = 49 | issue = 8 | pages = 487–498 | date = September 2011 | pmid = 22009816 | url = http://acta.tums.ac.ir/index.php/acta/article/view/4380 | access-date = 12 March 2014 }}</ref><ref>{{cite journal | vauthors = Heal DJ, Buckley NW, Gosden J, Slater N, France CP, Hackett D | title = A preclinical evaluation of the discriminative and reinforcing properties of lisdexamfetamine in comparison to D-amfetamine, methylphenidate and modafinil | journal = Neuropharmacology | volume = 73 | pages = 348–358 | date = October 2013 | pmid = 23748096 | doi = 10.1016/j.neuropharm.2013.05.021 | s2cid = 25343254 }}</ref><ref>{{cite journal | vauthors = Rowley HL, Kulkarni R, Gosden J, Brammer R, Hackett D, Heal DJ | title = Lisdexamfetamine and immediate release d-amfetamine - differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity | journal = Neuropharmacology | volume = 63 | issue = 6 | pages = 1064–1074 | date = November 2012 | pmid = 22796358 | doi = 10.1016/j.neuropharm.2012.07.008 | s2cid = 29702399 }}</ref>

====Adderall====
{{main|Chemistry:Adderall}}
[[File:Amph salts.jpg|thumb|alt=Adderall tablets|Adderall 20&nbsp;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.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> It is available as immediate release (IR) tablets and extended release (XR) capsules.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> Adderall contains equal amounts of four amphetamine salts:<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" />
* One-quarter racemic (d,l-)amphetamine aspartate [[Chemistry:Hydrate|monohydrate]]
* One-quarter dextroamphetamine [[Chemistry:Saccharic acid|saccharate]]
* One-quarter dextroamphetamine [[Chemistry:Sulfate|sulfate]]
* One-quarter racemic (d,l-)amphetamine sulfate

Adderall has a total amphetamine base equivalence of 63%.<ref name="Adderall FDA label" /><ref name="Adderall XR FDA label" /> While the enantiomer ratio by dextroamphetamine salts to levoamphetamine salts is 3:1,<!-- REF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666194/table/table1-0269881113482532/ --> the amphetamine base content is 75.9% dextroamphetamine, 24.1% levoamphetamine. {{#tag:ref|Calculated by dextroamphetamine base percent / total amphetamine base percent = 47.49/62.57 = 75.90% from table: Amphetamine base in marketed amphetamine medications. The remainder is levoamphetamine.| group = "note" }}

{{Amphetamine base in marketed amphetamine medications}}

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==Notes==
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==Reference notes==
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==References==
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==External links==
* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/dextroamphetamine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Dextroamphetamine }}
* {{cite book | url = http://www.inchem.org/documents/pims/pharm/pim178.htm | title = Poison Information Monograph | chapter = PIM 178: Dexamphetamine Sulphate) | publisher =  International Programme on Chemical Safety (IPCS) Chemical Safety Information from Intergovernmental organizations (INCHEM) }}

{{Amphetamine|state=expanded}}
{{ADHD pharmacotherapies}}
{{Monoamine releasing agents}}
{{TAAR ligands}}
{{Phenethylamines}}

[[Category:Anorectics]]
[[Category:Enantiopure drugs]]
[[Category:Euphoriants]]
[[Category:Excitatory amino acid reuptake inhibitors]]
[[Category:Nootropics]]
[[Category:Norepinephrine-dopamine releasing agents]]
[[Category:Phenethylamines]]
[[Category:Stimulants]]
[[Category:Substituted amphetamines]]
[[Category:TAAR1 agonists]]

{{Sourceattribution|Dextroamphetamine}}