Dextroamphetamine

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For the racemic compound, see Amphetamine.
Dextroamphetamine
Dexamfetamine2DACS.svg
Dexamfetamine3Dan.gif
Systematic (IUPAC) name
(2S)-1-phenylpropan-2-amine
Clinical data
Trade names Dexedrine, Dextrostat
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[note 1] is a potent psychostimulant and amphetamine stereoisomer prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults and the rare sleep disorder, 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. Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue.

The amphetamine molecule has two stereoisomers:[note 2] levoamphetamine and dextroamphetamine. Dextroamphetamine is the more active 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. Dextroamphetamine is also the active metabolite of the prodrug[note 3] lisdexamfetamine.

Dextroamphetamine, like other amphetamines, elicits its stimulating effects via two distinct actions: first, it inhibits the transporter proteins for the monoamine neurotransmitters (namely the serotonin, norepinephrine and dopamine transporters) via trace amine-associated receptor 1 (TAAR1); and second, it releases these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2. It also shares many chemical and pharmacological properties with the human trace amine neurotransmiters, especially phenethylamine and N-methylphenethylamine, the latter being an isomer of amphetamine that is produced within the human body.

Uses[edit]

Part of this section is transcluded from Amphetamine. (edit | history)

Medical[edit]

Dexedrine Spansule 5, 10 and 15 mg capsules

Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy, and is sometimes prescribed off-label for its past medical indications, such as depression, obesity, and nasal congestion.[10][11] Long-term amphetamine exposure in some species is known to produce abnormal dopamine system development or nerve damage,[12][13] but humans experience normal development and nerve growth.[14][15][16] Magnetic resonance imaging studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function of the right caudate nucleus.[14][15][16]

Reviews of clinical stimulant research have established the safety and effectiveness of long-term amphetamine use for ADHD.[17][18] Controlled trials spanning two years have demonstrated continuous treatment effectiveness and safety.[18][19] One review highlighted a 9 month randomized controlled trial in children that found an average increase of 4.5 IQ points and continued improvements in attention, disruptive behaviors, and hyperactivity.[19]

Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems,[note 4] particularly those involving dopamine and norepinephrine.[20] Psychostimulants like methylphenidate and amphetamine possess efficacy in treating ADHD because they increase neurotransmitter activity in these systems.[21][20][22] Approximately 70% of those who use these stimulants see improvements in ADHD symptoms.[23][24] Children with ADHD who use stimulant medications generally have better relationships with peers and family members,[17][23] generally perform better in school, are less distractible and impulsive, and have longer attention spans.[17][23] The Cochrane Collaboration's review[note 5] on the treatment of adult ADHD with amphetamines stated that amphetamines improve short-term symptoms, but have higher discontinuation rates than non-stimulant medications due to their adverse effects.[26]

A Cochrane Collaboration review on the treatment of ADHD in children with tic disorders indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine in such people should be avoided.[27] Other Cochrane reviews on the use of amphetamine for improving recovery following stroke or acute brain injury indicated that it may improve recovery, but further research is needed to confirm this.[28][29][30]

Performance-enhancing[edit]

Therapeutic doses of amphetamine improve cortical network efficiency, resulting in higher performance on working memory tests in all individuals.[21][31] Amphetamine and other ADHD stimulants also improve task saliency and increase arousal.[21][32] Stimulants such as amphetamine can improve performance on difficult and boring tasks,[21][32] and are used by some students as a study and test-taking aid.[33] Based upon studies of self-reported illicit stimulant use, performance-enhancing use, rather than abuse as a recreational drug, is the primary reason that students use stimulants.[34] High amphetamine doses, above the therapeutic range, can interfere with working memory and cognitive control.[21][32]

Amphetamine is used by some athletes for its psychological and performance-enhancing effects, such as increased stamina and alertness, but this is prohibited at events regulated by the World Anti-Doping Agency.[35][36][37] In healthy people at oral therapeutic doses, amphetamine has been shown to increase physical strength,[37][38] acceleration,[37][38] stamina,[37][39] endurance,[37][39] and alertness,[35] while reducing reaction time.[37] Like the psychostimulants methylphenidate and bupropion, amphetamine increases stamina and endurance in humans primarily through reuptake inhibition and effluxion of dopamine in the central nervous system.[38][39] At much higher doses, amphetamine can induce side effects that impair performance, such as rhabdomyolysis and hyperthermia.[40][41][38]

Contraindications[edit]

This section is transcluded from Amphetamine. (edit | history)

According to the International Programme on Chemical Safety (IPCS) and United States Food and Drug Administration (USFDA),[note 6] amphetamine is contraindicated in people with a history of drug abuse, heart disease, severe agitation, or severe anxiety.[42][43] It is also contraindicated in people currently experiencing arteriosclerosis, glaucoma, hyperthyroidism, or severe hypertension.[42][43] People who have experienced hypersensitivity reactions to other stimulants in the past or are taking monoamine oxidase inhibitors (MAOIs) are advised not to take amphetamine.[42][43] These agencies also state that anyone with anorexia nervosa, bipolar disorder, depression, elevated blood pressure, liver or kidney problems, mania, psychosis, Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome should monitor their symptoms while taking amphetamine.[42][43] Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in the fetus or newborns (i.e., it is not a human teratogen), but amphetamine abuse does pose risks to the fetus.[43] Amphetamine has also been shown to pass into breast milk, so the IPCS and USFDA advise mothers to avoid breastfeeding when using it.[42][43] Due to the potential for stunted growth, the USFDA advises monitoring the height and weight of children and adolescents prescribed amphetamines.[42]

Side effects[edit]

Part of this section is transcluded from Amphetamine. (edit | history)

The Cochrane Collaboration review on amphetamines for ADHD suggests that dextroamphetamine and other amphetamine mixtures have the same incidence of adverse events.[26]

Physical

At normal therapeutic doses, the physical side effects of amphetamine vary widely by age and among individual people.[41] Cardiovascular side effects can include irregular heartbeat (usually increased heart rate), hypertension (high blood pressure) or hypotension (low blood pressure) from a vasovagal response, and Raynaud's phenomenon.[41][35][44] Sexual side effects in males may include erectile dysfunction, frequent erections, or prolonged erections. Other potential side effects include abdominal pain, acne, blurred vision, excessive grinding of the teeth, profuse sweating, dry mouth, loss of appetite, nausea, reduced seizure threshold, tics, and weight loss.[41][35][44] Dangerous physical side effects are rare in typical pharmaceutical doses.[35]

Amphetamine stimulates the medullary respiratory centers, producing faster and deeper breaths.[35] In a normal person at therapeutic doses, amphetamine does not noticeably stimulate breathing, but when respiration is already compromised, it may stimulate it.[35] Amphetamine also induces contraction in the urinary bladder sphincter, the muscle which controls urination, which can result in difficulty urinating; this effect can be useful in treating bed wetting and loss of bladder control.[35] The effects of amphetamine on the gastrointestinal tract are unpredictable.[35] Amphetamine may reduce gastrointestinal motility (i.e., intestinal peristalsis) if intestinal activity is high, or increase motility if the smooth muscle of the tract is relaxed.[35] Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opiates.[35]

USFDA commissioned studies from 2011 indicate that, in children, young adults, and adults, there is no association between serious adverse cardiovascular events (sudden death, heart attack, and stroke) and the medical use of amphetamine or other ADHD stimulants.[sources 1]

Psychological

Common psychological effects of therapeutic doses can include alertness, apprehension, concentration, decreased sense of fatigue, mood swings (elated mood followed by mildly depressed mood), increased initiative, insomnia or wakefulness, self-confidence, and sociability.[41][35] Less commonly, depending on the user's personality and current mental state, anxiety, change in libido, grandiosity, irritability, repetitive or obsessive behaviors, and restlessness can occur.[sources 2] Amphetamine psychosis can occur in heavy users.[40][41][51] Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy.[40][41][52] According to the USFDA, "there is no systematic evidence that stimulants cause aggressive behavior or hostility."[41]

Overdose[edit]

This section is transcluded from Amphetamine. (edit | history)

An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care.[43][53] A moderate overdose may induce symptoms including brisk reflexes, confusion, high or low blood pressure, hyperthermia, inability to urinate, involuntary muscle twitching, irregular heartbeat, muscle pain, painful urination, rapid breathing, and severe agitation.[40][35][43] An extremely large overdose may produce symptoms such as amphetamine psychosis, bleeding in the brain, cardiogenic shock, circulatory collapse, compulsive and repetitive behavior, elevated blood potassium or low blood potassium, extreme fever, fluid accumulation in the lungs, high lung arterial blood pressure, kidney failure, metabolic acidosis, no urine production, rapid muscle breakdown, respiratory alkalosis, serotonin toxidrome, and sympathomimetic toxidrome.[sources 3] Fatal amphetamine poisoning usually involves convulsions and coma.[40][35]

Dependence, addiction, and withdrawal

Addiction is a serious risk with heavy recreational amphetamine use; it is unlikely to arise from typical medical use.[40][56][35] Tolerance develops rapidly in amphetamine abuse, so periods of extended use require increasing doses of the drug in order to achieve the same effect.[57][58]

A Cochrane Collaboration review on amphetamine and methamphetamine dependence and abuse indicates that the current evidence on effective treatments is extremely limited.[59] The review indicated that fluoxetine[note 7] and imipramine[note 8] have some limited benefits in treating abuse and addiction, but concluded, "no treatment has been demonstrated to be effective for the treatment of amphetamine dependence and abuse."[59] A corroborating review indicated that amphetamine dependence is mediated through increased activation of dopamine receptors and co-localized NMDA receptors in the mesolimbic pathway.[60] This review also noted that magnesium ions, which inhibit NMDA receptor calcium channels, and serotonin have inhibitory effects on NMDA receptors.[60] It also suggested that, based upon animal testing, pathological amphetamine use significantly reduces the level of intracellular magnesium throughout the brain.[60] Supplemental magnesium,[note 9] like fluoxetine treatment, has been shown to reduce self-administration in both humans and lab animals.[59][60]

According to another 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."[61] This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in up to 87.6% of cases, and persist for three to four weeks with a marked "crash" phase occurring during the first week.[61] Amphetamine withdrawal symptoms can include anxiety, drug craving, depressed mood, fatigue, increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams.[61] The review suggested that withdrawal symptoms are associated with the degree of dependence, suggesting that therapeutic use would result in far milder discontinuation symptoms.[61] Manufacturer prescribing information does not indicate the presence of withdrawal symptoms following discontinuation of amphetamine use after an extended period at therapeutic doses.[62][63][64]

Current models of addiction from chronic drug use involve alterations in gene expression in certain parts of the brain.[65][66][67] The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB).[66] ΔFosB is the most significant, since its overexpression in the nucleus accumbens is necessary and sufficient for many of the neural adaptations seen in drug addiction;[66] it has been implicated in addictions to alcohol, cannabinoids, cocaine, nicotine, phenylcyclidine, and substituted amphetamines.[65][66][68] ΔJunD is the transcription factor which directly opposes ΔFosB.[66] Increases in nucleus accumbens ΔJunD expression can reduce or, with a large increase, even block most of the neural alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).[66] ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[66][69] Since natural rewards, like drugs of abuse, induce ΔFosB, chronic acquisition of these rewards can result in a similar pathological addictive state.[66][69] Consequently, ΔFosB is the key transcription factor involved in amphetamine addiction, especially amphetamine-induced sex addictions.[66][69][70] ΔFosB inhibitors (drugs that oppose its action) may be an effective treatment for addiction and addictive disorders.[71]

The effects of amphetamine on gene regulation are both dose- and route-dependent.[67] Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses.[67] The few studies that have used equivalent (weight-adjusted) human therapeutic doses and oral administration show that these changes, if they occur, are relatively minor.[67]

Psychosis

The main section for this topic is on the page Stimulant psychosis, in the section Substituted amphetamines.

Abuse of amphetamine can result in a stimulant psychosis that may present with a variety of symptoms (e.g., paranoia, hallucinations, delusions).[51] A Cochrane Collaboration review on treatment for amphetamine, dextroamphetamine, and methamphetamine abuse-induced psychosis states that about 5–15% of users fail to recover completely.[51][72] The same review asserts that, based upon at least one trial, antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[51] Psychosis very rarely arises from therapeutic use.[52][42]

Toxicity

In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity, or damage to dopamine neurons, which is characterized as reduced transporter and receptor function.[73] There is no evidence that amphetamine is directly neurotoxic in humans.[74][75] High-dose amphetamine can cause indirect neurotoxicity as a result of increased oxidative stress from reactive oxygen species and autoxidation of dopamine.[12][76][77]

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.[78][79] 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).[78][80][81] Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called VMAT2.[82] When amphetamine is taken up by VMAT2, the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.[82]

Dextroamphetamine (the dextrorotary enantiomer) and levoamphetamine (the levorotary enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary.[79][35] Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine.[79] Consequently, dextroamphetamine produces roughly three to four times more central nervous system (CNS) stimulation than levoamphetamine;[79][35] however, levoamphetamine has slightly greater cardiovascular and peripheral effects.[35]

Related endogenous compounds[edit]

For more details on related compounds, see Trace amines.

Amphetamine has a very similar structure and function to the endogenous trace amines, which are naturally occurring neurotransmitter molecules produced in the human body and brain.[81][83] Among this group, the most closely related compounds are phenethylamine, the parent compound of amphetamine, and N-methylphenethylamine, an isomer of amphetamine (i.e., it has an identical molecular formula).[81][83][84] In humans, phenethylamine is produced directly from L-phenylalanine by the aromatic amino acid decarboxylase (AADC) enzyme, which converts L-DOPA into dopamine as well.[83][84] In turn, N‑methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine.[83][84] Like amphetamine, both phenethylamine and N‑methylphenethylamine regulate monoamine neurotransmission via TAAR1;[81][84] unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.[83][84]

Pharmacokinetics[edit]

Amphetamine is well absorbed from the gut, and bioavailability is typically over 75% for dextroamphetamine.[85] However, oral availability varies with gastrointestinal pH.[86] 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][86] Conversely, an acidic pH means the drug is predominantly in its water soluble cationic form, and less is absorbed.[2][86]

Approximately 15–40% of dextroamphetamine circulating in the bloodstream is bound to plasma proteins.[87]

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.[88][89] 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.[88] Apparent half-life and duration of effect increase with repeated use and accumulation of the drug.[90]

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][91] Amphetamine has a variety of excreted metabolic products, including 4-hydroxyamfetamine, 4-hydroxynorephedrine, 4-hydroxyphenylacetone, benzoic acid, hippuric acid, norephedrine, and phenylacetone.[2][88][92] Among these metabolites, the active sympathomimetics are 4‑hydroxyamphetamine,[93] 4‑hydroxynorephedrine,[94] and norephedrine.[95]

The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.[2][88] The known pathways include:[2][4][92]

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;[92] 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.[96] 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,[note 10] 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.[97] In the United States, Dexedrine was approved to treat narcolepsy, attention disorders, depression, and obesity. In Canada, epilepsy and parkinsonism were also approved indications.[98] 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").[99] Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue.[100]

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.[101] 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).[102]

In October 2010, GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).[103]

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".[104][105][106][107] 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.[105]

Formulations[edit]

Pharmaceuticals
Brand
name
United States
Adopted Name
(D:L) ratio
of salts
Dosage
form
Source
Adderall 3:1 tablet [108][109]
Adderall XR 3:1 capsule [108][109]
Dexedrine dextroamphetamine sulfate 1:0 capsule [108][109]
ProCentra dextroamphetamine sulfate 1:0 liquid [109]
Vyvanse lisdexamfetamine dimesylate 1:0 capsule [108][110]
Zenzedi dextroamphetamine sulfate 1:0 tablet [109]
 
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,[111] 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.[112]

In Australia, dexamfetamine is available in bottles of 100 instant release 5 mg tablets as a generic drug.[113] or slow release dexamfetamine preparations may be compounded by individual chemists.[114] 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).[115]

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.[116] 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,[117] thus a 30 mg-strength Vyvanse capsule is molecularly equivalent to 8.844 mg dexamfetamine base.

Amphetamine salts (Adderall)[edit]

Adderall tablets
Adderall 20 mg tablets, some broken in half, with a lengthwise-folded US dollar bill along the bottom
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. ^ "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. ^ Heal DJ, Smith SL, Gosden J, Nutt DJ (June 2013). "Amphetamine, past and present – a pharmacological and clinical perspective". J. Psychopharmacol. 27 (6): 479–96. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642. 
  11. ^ "DEXEDRINE (dextroamphetamine sulfate) tablet [Amedra Pharmaceuticals LLC]". DailyMed. Horsham, USA: Amedra Pharmaceuticals LLC. June 2014. Retrieved 18 July 2014. 
  12. ^ a b Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos Mde L (August 2012). "Toxicity of amphetamines: an update". Arch. Toxicol. 86 (8): 1167–1231. doi:10.1007/s00204-012-0815-5. PMID 22392347. 
  13. ^ Berman S, O'Neill J, Fears S, Bartzokis G, London ED (2008). "Abuse of amphetamines and structural abnormalities in the brain". Ann. N. Y. Acad. Sci. 1141: 195–220. doi:10.1196/annals.1441.031. PMC 2769923. PMID 18991959. 
  14. ^ a b Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K (February 2013). "Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects". JAMA Psychiatry 70 (2): 185–198. doi:10.1001/jamapsychiatry.2013.277. PMID 23247506. 
  15. ^ a b Spencer TJ, Brown A, Seidman LJ, Valera EM, Makris N, Lomedico A, Faraone SV, Biederman J (September 2013). "Effect of psychostimulants on brain structure and function in ADHD: a qualitative literature review of magnetic resonance imaging-based neuroimaging studies". J. Clin. Psychiatry 74 (9): 902–917. doi:10.4088/JCP.12r08287. PMC 3801446. PMID 24107764. 
  16. ^ a b Frodl T, Skokauskas N (February 2012). "Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.". Acta psychiatrica Scand. 125 (2): 114–126. doi:10.1111/j.1600-0447.2011.01786.x. PMID 22118249. "Basal ganglia regions like the right globus pallidus, the right putamen, and the nucleus caudatus are structurally affected in children with ADHD. These changes and alterations in limbic regions like ACC and amygdala are more pronounced in non-treated populations and seem to diminish over time from child to adulthood. Treatment seems to have positive effects on brain structure." 
  17. ^ a b c Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 111–113. ISBN 9781441913968. 
  18. ^ a b Huang YS, Tsai MH (July 2011). "Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge". CNS Drugs 25 (7): 539–554. doi:10.2165/11589380-000000000-00000. PMID 21699268. 
  19. ^ a b Millichap JG (2010). "Chapter 3: Medications for ADHD". In Millichap JG. Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD (2nd ed.). New York: Springer. pp. 121–123. ISBN 9781441913968. 
  20. ^ a b c Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 154–157. ISBN 9780071481274. 
  21. ^ a b c d e Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 318. ISBN 9780071481274. "Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in in normal subjects and those with ADHD. Positron emission tomography (PET) demonstrates that methylphenidate decreases regional cerebral blood flow in the doroslateral prefrontal cortex and posterior parietal cortex while improving performance of a spacial working memory task. This suggests that cortical networks that normally process spatial working memory become more efficient in response to the drug. ... [It] is now believed that dopamine and norepinephrine, but not serotonin, produce the beneficial effects of stimulants on working memory. At abused (relatively high) doses, stimulants can interfere with working memory and cognitive control ... stimulants act not only on working memory function, but also on general levels of arousal and, within the nucleus accumbens, improve the saliency of tasks. Thus, stimulants improve performance on effortful but tedious tasks ... through indirect stimulation of dopamine and norepinephrine receptors." 
  22. ^ Bidwell LC, McClernon FJ, Kollins SH (August 2011). "Cognitive enhancers for the treatment of ADHD". Pharmacol. Biochem. Behav. 99 (2): 262–274. doi:10.1016/j.pbb.2011.05.002. PMC 3353150. PMID 21596055. 
  23. ^ a b c "Stimulants for Attention Deficit Hyperactivity Disorder". WebMD. Healthwise. 12 April 2010. Retrieved 12 November 2013. 
  24. ^ Greenhill LL, Pliszka S, Dulcan MK, Bernet W, Arnold V, Beitchman J, Benson RS, Bukstein O, Kinlan J, McClellan J, Rue D, Shaw JA, Stock S (February 2002). "Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults". J. Am. Acad. Child Adolesc. Psychiatry 41 (2 Suppl): 26S–49S. PMID 11833633. 
  25. ^ Scholten RJ, Clarke M, Hetherington J (August 2005). "The Cochrane Collaboration". Eur. J. Clin. Nutr. 59 Suppl 1: S147–S149; discussion S195–S196. doi:10.1038/sj.ejcn.1602188. PMID 16052183. 
  26. ^ a b Castells X, Ramos-Quiroga JA, Bosch R, Nogueira M, Casas M (2011). "Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults". In Castells X. Cochrane Database Syst. Rev. (6): CD007813. doi:10.1002/14651858.CD007813.pub2. PMID 21678370. 
  27. ^ Pringsheim T, Steeves T (April 2011). "Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders". In Pringsheim T. Cochrane Database Syst. Rev. (4): CD007990. doi:10.1002/14651858.CD007990.pub2. PMID 21491404. 
  28. ^ Martinsson L, Hårdemark H, Eksborg S (January 2007). "Amphetamines for improving recovery after stroke". In Martinsson L. Cochrane Database Syst. Rev. (1): CD002090. doi:10.1002/14651858.CD002090.pub2. PMID 17253474. 
  29. ^ Forsyth RJ, Jayamoni B, Paine TC (October 2006). "Monoaminergic agonists for acute traumatic brain injury". In Forsyth RJ. Cochrane Database Syst. Rev. (4): CD003984. doi:10.1002/14651858.CD003984.pub2. PMID 17054192. 
  30. ^ Harbeck-Seu A, Brunk I, Platz T, Vajkoczy P, Endres M, Spies C (April 2011). "A speedy recovery: amphetamines and other therapeutics that might impact the recovery from brain injury". Curr. Opin. Anaesthesiol. 24 (2): 144–153. doi:10.1097/ACO.0b013e328344587f. PMID 21386667. 
  31. ^ Devous MD, Trivedi MH, Rush AJ (April 2001). "Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers". J. Nucl. Med. 42 (4): 535–42. PMID 11337538. 
  32. ^ a b c Wood S, Sage JR, Shuman T, Anagnostaras SG (January 2014). "Psychostimulants and cognition: a continuum of behavioral and cognitive activation". Pharmacol. Rev. 66 (1): 193–221. doi:10.1124/pr.112.007054. PMID 24344115. 
  33. ^ Twohey M (26 March 2006). "Pills become an addictive study aid". JS Online. Archived from the original on 15 August 2007. Retrieved 2 December 2007. 
  34. ^ Teter CJ, McCabe SE, LaGrange K, Cranford JA, Boyd CJ (October 2006). "Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration". Pharmacotherapy 26 (10): 1501–1510. doi:10.1592/phco.26.10.1501. PMC 1794223. PMID 16999660. 
  35. ^ a b c d e f g h i j k l m n o p q r s t 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. 
  36. ^ Bracken NM (January 2012). "National Study of Substance Use Trends Among NCAA College Student-Athletes". NCAA Publications. National Collegiate Athletic Association. Retrieved 8 October 2013. 
  37. ^ a b c d e f Liddle DG, Connor DJ (June 2013). "Nutritional supplements and ergogenic AIDS". Prim. Care 40 (2): 487–505. doi:10.1016/j.pop.2013.02.009. PMID 23668655. "Amphetamines and caffeine are stimulants that increase alertness, improve focus, decrease reaction time, and delay fatigue, allowing for an increased intensity and duration of training ...
    Physiologic and performance effects
     • Amphetamines increase dopamine/norepinephrine release and inhibit their reuptake, leading to central nervous system (CNS) stimulation
     • Amphetamines seem to enhance athletic performance in anaerobic conditions 39 40
     • Improved reaction time
     • Increased muscle strength and delayed muscle fatigue
     • Increased acceleration
     • Increased alertness and attention to task"
     
  38. ^ a b c d Parr JW (July 2011). "Attention-deficit hyperactivity disorder and the athlete: new advances and understanding". Clin Sports Med 30 (3): 591–610. doi:10.1016/j.csm.2011.03.007. PMID 21658550. 
  39. ^ a b c Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R (May 2013). "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing". Sports Med. 43 (5): 301–311. doi:10.1007/s40279-013-0030-4. PMID 23456493. 
  40. ^ a b c d e f g "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. p. 11. Retrieved 30 December 2013. 
  41. ^ a b c d e f g h i "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 4–8. Retrieved 30 December 2013. 
  42. ^ a b c d e f g "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 4–6. Retrieved 30 December 2013. 
  43. ^ a b c d e f g h Heedes G; Ailakis J. "Amphetamine (PIM 934)". INCHEM. International Programme on Chemical Safety. Retrieved 24 June 2014. 
  44. ^ a b Vitiello B (April 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): 459–474. doi:10.1016/j.chc.2007.11.010. PMC 2408826. PMID 18295156. 
  45. ^ "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in children and young adults". United States Food and Drug Administration. 20 December 2011. Retrieved 4 November 2013. 
  46. ^ Cooper WO, Habel LA, Sox CM, Chan KA, Arbogast PG, Cheetham TC, Murray KT, Quinn VP, Stein CM, Callahan ST, Fireman BH, Fish FA, Kirshner HS, O'Duffy A, Connell FA, Ray WA (November 2011). "ADHD drugs and serious cardiovascular events in children and young adults". N. Engl. J. Med. 365 (20): 1896–1904. doi:10.1056/NEJMoa1110212. PMID 22043968. 
  47. ^ "FDA Drug Safety Communication: Safety Review Update of Medications used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) in adults". United States Food and Drug Administration. 15 December 2011. Retrieved 4 November 2013. 
  48. ^ Habel LA, Cooper WO, Sox CM, Chan KA, Fireman BH, Arbogast PG, Cheetham TC, Quinn VP, Dublin S, Boudreau DM, Andrade SE, Pawloski PA, Raebel MA, Smith DH, Achacoso N, Uratsu C, Go AS, Sidney S, Nguyen-Huynh MN, Ray WA, Selby JV (December 2011). "ADHD medications and risk of serious cardiovascular events in young and middle-aged adults". JAMA 306 (24): 2673–2683. doi:10.1001/jama.2011.1830. PMC 3350308. PMID 22161946. 
  49. ^ Montgomery KA (June 2008). "Sexual desire disorders". Psychiatry (Edgmont) 5 (6): 50–55. PMC 2695750. PMID 19727285. 
  50. ^ O'Connor PG (February 2012). "Amphetamines". Merck Manual for Health Care Professionals. Merck. Retrieved 8 May 2012. 
  51. ^ a b c d Shoptaw SJ, Kao U, Ling W (2009). "Treatment for amphetamine psychosis". In Shoptaw SJ, Ali R. Cochrane Database Syst. Rev. (1): CD003026. doi:10.1002/14651858.CD003026.pub3. PMID 19160215. "A minority of individuals who use amphetamines develop full-blown psychosis requiring care at emergency departments or psychiatric hospitals. In such cases, symptoms of amphetamine psychosis commonly include paranoid and persecutory delusions as well as auditory and visual hallucinations in the presence of extreme agitation. More common (about 18%) is for frequent amphetamine users to report psychotic symptoms that are sub-clinical and that do not require high-intensity intervention ...
    About 5–15% of the users who develop an amphetamine psychosis fail to recover completely (Hofmann 1983) ...
    Findings from one trial indicate use of antipsychotic medications effectively resolves symptoms of acute amphetamine psychosis."
     
  52. ^ a b Greydanus D. "Stimulant Misuse: Strategies to Manage a Growing Problem". American College Health Association (Review Article). ACHA Professional Development Program. p. 20. Retrieved 2 November 2013. 
  53. ^ 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. "Amphetamine, dextroamphetamine, and methylphenidate act as substrates for the cellular monoamine transporter, especially the dopamine transporter (DAT) and less so the norepinephrine (NET) and serotonin transporter. The mechanism of toxicity is primarily related to excessive extracellular dopamine, norepinephrine, and serotonin." 
  54. ^ Greene SL, Kerr F, Braitberg G (October 2008). "Review article: amphetamines and related drugs of abuse". Emerg. Med. Australas 20 (5): 391–402. doi:10.1111/j.1742-6723.2008.01114.x. PMID 18973636. 
  55. ^ 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. 
  56. ^ Stolerman IP (2010). Stolerman IP, ed. Encyclopedia of Psychopharmacology. Berlin; London: Springer. p. 78. ISBN 9783540686989. 
  57. ^ "Amphetamines: Drug Use and Abuse". Merck Manual Home Edition. Merck. February 2003. Archived from the original on 17 February 2007. Retrieved 28 February 2007. 
  58. ^ Pérez-Mañá C, Castells X, Torrens M, Capellà D, Farre M (2013). "Efficacy of psychostimulant drugs for amphetamine abuse or dependence". In Pérez-Mañá C. Cochrane Database Syst. Rev. 9: CD009695. doi:10.1002/14651858.CD009695.pub2. PMID 23996457. 
  59. ^ a b c d e Srisurapanont M, Jarusuraisin N, Kittirattanapaiboon P (2001). "Treatment for amphetamine dependence and abuse". In Srisurapanont M. Cochrane Database Syst. Rev. (4): CD003022. doi:10.1002/14651858.CD003022. PMID 11687171. "Although there are a variety of amphetamines and amphetamine derivatives, the word "amphetamines" in this review stands for amphetamine, dextroamphetamine and methamphetamine only." 
  60. ^ a b c d e Nechifor M (March 2008). "Magnesium in drug dependences". Magnes. Res. 21 (1): 5–15. PMID 18557129. 
  61. ^ 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) ..."
     
  62. ^ "Adderall IR Prescribing Information". United States Food and Drug Administration. March 2007. Retrieved 4 November 2013. 
  63. ^ "Dexedrine Medication Guide". United States Food and Drug Administration. May 2013. Retrieved 4 November 2013. 
  64. ^ "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. Retrieved 30 December 2013. 
  65. ^ a b Hyman SE, Malenka RC, Nestler EJ (2006). "Neural mechanisms of addiction: the role of reward-related learning and memory". Annu. Rev. Neurosci. 29: 565–598. doi:10.1146/annurev.neuro.29.051605.113009. PMID 16776597. 
  66. ^ a b c d e f g h i Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. "ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states." 
  67. ^ a b c d Steiner H, Van Waes V (January 2013). "Addiction-related gene regulation: risks of exposure to cognitive enhancers vs. other psychostimulants". Prog. Neurobiol. 100: 60–80. doi:10.1016/j.pneurobio.2012.10.001. PMC 3525776. PMID 23085425. 
  68. ^ Kanehisa Laboratories (2 August 2013). "Alcoholism – Homo sapiens (human)". KEGG Pathway. Retrieved 10 April 2014. 
  69. ^ a b c Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". J. Psychoactive Drugs 44 (1): 38–55. PMC 4040958. PMID 22641964. 
  70. ^ Pitchers KK, Frohmader KS, Vialou V, Mouzon E, Nestler EJ, Lehman MN, Coolen LM (October 2010). "ΔFosB in the nucleus accumbens is critical for reinforcing effects of sexual reward". Genes Brain Behav. 9 (7): 831–840. doi:10.1111/j.1601-183X.2010.00621.x. PMC 2970635. PMID 20618447. 
  71. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and addictive disorders". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 384–385. ISBN 9780071481274. 
  72. ^ Hofmann FG (1983). A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects (2nd ed.). New York: Oxford University Press. p. 329. ISBN 9780195030570. 
  73. ^ Advokat C (2007). "Update on amphetamine neurotoxicity and its relevance to the treatment of ADHD". J. Atten. Disord. 11 (1): 8–16. doi:10.1177/1087054706295605. PMID 17606768. 
  74. ^ "Amphetamine". Hazardous Substances Data Bank. National Library of Medicine. Retrieved 26 February 2014. "Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation." 
  75. ^ Malenka RC, Nestler EJ, Hyman SE (2009). "15". In Sydor A, Brown RY. Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 370. ISBN 9780071481274. "Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons." 
  76. ^ Sulzer D, Zecca L (February 2000). "Intraneuronal dopamine-quinone synthesis: a review". Neurotox. Res. 1 (3): 181–195. doi:10.1007/BF03033289. PMID 12835101. 
  77. ^ Miyazaki I, Asanuma M (June 2008). "Dopaminergic neuron-specific oxidative stress caused by dopamine itself". Acta Med. Okayama 62 (3): 141–150. PMID 18596830. 
  78. ^ 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. 
  79. ^ 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. 
  80. ^ 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. 
  81. ^ 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. 
  82. ^ 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. 
  83. ^ 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 ... 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 ..."
     
  84. ^ a b c d e Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/j.tips.2005.03.007. PMID 15860375. "In addition to the main metabolic pathway, TAs can also be converted by nonspecific N-methyltransferase (NMT) [22] and phenylethanolamine N-methyltransferase (PNMT) [23] to the corresponding secondary amines (e.g. synephrine [14], N-methylphenylethylamine and N-methyltyramine [15]), which display similar activities on TAAR1 (TA1) as their primary amine precursors." 
  85. ^ Pharmacology. "Dextroamphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 5 November 2013. 
  86. ^ a b c "Adderall XR Prescribing Information". United States Food and Drug Administration. December 2013. pp. 8–10. Retrieved 30 December 2013. 
  87. ^ Pharmacology. "Amphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 5 November 2013. 
  88. ^ a b c d Biomedical Effects and Toxicity. "Amphetamine". Pubchem Compound. National Center for Biotechnology Information. Retrieved 12 October 2013. 
  89. ^ 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%." 
  90. ^ 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. 
  91. ^ Enzymes. "Amphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 30 September 2013. 
  92. ^ 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. 
  93. ^ Compound Summary. "p-Hydroxyamphetamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  94. ^ Compound Summary. "p-Hydroxynorephedrine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  95. ^ Compound Summary. "Phenylpropanolamine". PubChem Compound. National Center for Biotechnology Information. Retrieved 15 October 2013. 
  96. ^ Help For Dexedrine Addicts | Dexedrine Rehab Centers For Addicts
  97. ^ "Dexedrine". Medic8. Retrieved 27 November 2013. 
  98. ^ Dextroamphetamine: Canadian Drug Monograph
  99. ^ Information on Dexedrine: A Quick Review | Weitz & Luxenberg
  100. ^ Heal, DJ; Smith, SL; Gosden, J; Nutt, DJ (June 2013). "Amphetamine, past and present--a pharmacological and clinical perspective.". Journal of Psychopharmacology 27 (6): 479–96. doi:10.1177/0269881113482532. PMC 3666194. PMID 23539642. 
  101. ^ Prescription Forgery | Handwriting Services International
  102. ^ Pharmaceutical Manufacturing Encyclopedia (2nd edition), Marshall Sittig, Volume 1, Noyes Publications ISBN 978-0-8155-1144-1
  103. ^ "Dexedrine FAQs". 
  104. ^ http://www.nbcnews.com/id/3071789/ns/us_news-only/t/go-pills-war-drugs/
  105. ^ a b Air Force scientists battle aviator fatigue
  106. ^ 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. 
  107. ^ ‘Go pills’: A war on drugs?, msnbc, 9 January 2003
  108. ^ a b c d Description, Synonyms, Brand names, and Brand mixtures. "Amphetamine". DrugBank. University of Alberta. 8 February 2013. Retrieved 13 October 2013. 
  109. ^ 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. 
  110. ^ Identification. "Lisdexamfetamine". Drugbank. University of Alberta. 8 February 2013. Retrieved 13 October 2013. 
  111. ^ http://www.goodrx.com/dextrostat/images
  112. ^ FSC Laboratories: ProCentra (dextroamphetamine sulfate | 5 mg/5 mL Oral Solution)
  113. ^ Australian Prescriber | Stimulant treatment for attention deficit hyperactivity disorder
  114. ^ http://www0.health.nsw.gov.au/PublicHealth/Pharmaceutical/adhd/faqs.asp
  115. ^ "Red/Amber News Iss. 22", p2. Interface Pharmacist Network Specialist Medicines (IPNSM). www.ipnsm.hscni.net. Retrieved 20 April 2012.
  116. ^ FDA Approval of Vyvanse Pharmacological Reviews Pages 18 and 19
  117. ^ 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. ^ Synonyms and alternate spellings include dexamphetamine (AAN) and dexamfetamine (INN and BAN).
  2. ^ which are mirror images of the same molecule
  3. ^ that is, a drug that is metabolised in the body into another more biologically-active drug
  4. ^ This involves impaired dopamine neurotransmission in the mesocortical and mesolimbic pathways and norepinephrine neurotransmission in the prefrontal cortex and locus coeruleus.[20]
  5. ^ Cochrane Collaboration reviews are high quality meta-analytic systematic reviews of randomized controlled trials.[25]
  6. ^ The statements supported by the USFDA come from prescribing information, which is the copyrighted intellectual property of the manufacturer and approved by the USFDA.
  7. ^ During short-term treatment, fluoxetine may decrease drug craving.[59]
  8. ^ During "medium-term treatment," imipramine may extend the duration of adherence to addiction treatment.[59]
  9. ^ The review indicated that magnesium L-aspartate and magnesium chloride produce significant changes in addictive behavior;[60] other forms of magnesium were not mentioned.
  10. ^ Free-base form amphetamine is a volatile oil, hence the efficacy of the inhalers.

Reference notes[edit]

  1. ^ [45][46][47][48]
  2. ^ [49][41][35][50]
  3. ^ [54][40][35][53][55]

External links[edit]