Dextroamphetamine
(Redirected from
D-amphetamine
)
 | |
| Clinical data | |
|---|---|
| Pronunciation | /ˌdɛkstroʊæmˈfɛtəmiːn/ |
| Trade names | Dexedrine, Zenzedi, Xelstrym, others |
| Other names | d-Amphetamine, (S)-Amphetamine, S(+)-Amphetamine |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a605027 |
| License data | |
| Pregnancy category |
|
| Dependence liability | Moderate[1][2] - high[3][4][5] |
| Addiction liability | Moderate[1][2] - high[3][4][5] |
| Routes of administration | By mouth, transdermal |
| ATC code | |
| Legal status | |
| Legal status |
|
| Onset of action | IR dosing: 0.5–1.5 hours[15][16] XR dosing: 1.5–2 hours[17][18] |
| Elimination half-life | 9–11 hours[19][20] pH-dependent: 7–34 hours[21] |
| Duration of action | IR dosing: 3–6 hours[17][22] XR dosing: 8–12 hours[23][17][22] |
| Excretion | Kidney (45%);[24] urinary pH-dependent |
| Identifiers | |
| |
JSmol) | |
| Density | 0.913 g/cm3 |
| Boiling point | 201.5 °C (394.7 °F) |
| Solubility in water | 20 |
| |
| |
  (what is this?) (verify) | |
Dextroamphetamine (INN:dexamfetamine) is a potent
euphoriant
.
The amphetamine molecule exists as two enantiomers,lisdexamfetamine dimesylate, which is converted into dextroamphetamine after absorption.
Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or
N-methylphenethylamine, the latter being an isomer
of amphetamine produced within the human body.
Uses
Medical
Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and
Long-term amphetamine exposure at sufficiently high doses in some animal species is known to produce abnormal dopamine system development or nerve damage,[31][32] but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth.[33][34][35] Reviews of magnetic resonance imaging (MRI) studies suggest that long-term treatment with amphetamine decreases abnormalities in brain structure and function found in subjects with ADHD, and improves function in several parts of the brain, such as the right caudate nucleus of the basal ganglia.[33][34][35]Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD.[36][37][38] Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety.[36][37] Two reviews have indicated that long-term continuous stimulant therapy for ADHD is effective for reducing the core symptoms of ADHD (i.e., hyperactivity, inattention, and impulsivity), enhancing quality of life and academic achievement, and producing improvements in a large number of functional outcomes[note 2] across 9 categories of outcomes related to academics, antisocial behavior, driving, non-medicinal drug use, obesity, occupation, self-esteem, service use (i.e., academic, occupational, health, financial, and legal services), and social function.[36][38] One review highlighted a nine-month randomized controlled trial of amphetamine treatment for ADHD in children that found an average increase of 4.5 IQ points, continued increases in attention, and continued decreases in disruptive behaviors and hyperactivity.[37] Another review indicated that, based upon the longest follow-up studies conducted to date, lifetime stimulant therapy that begins during childhood is continuously effective for controlling ADHD symptoms and reduces the risk of developing a substance use disorder as an adult.[36]
Current models of ADHD suggest that it is associated with functional impairments in some of the brain's
mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to the prefrontal cortex.[39] Psychostimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems.[40][39][41] Approximately 80% of those who use these stimulants see improvements in ADHD symptoms.[42] Children with ADHD who use stimulant medications generally have better relationships with peers and family members, perform better in school, are less distractible and impulsive, and have longer attention spans.[43][44] The Cochrane reviews[note 3] on the treatment of ADHD in children, adolescents, and adults with pharmaceutical amphetamines stated that short-term studies have demonstrated that these drugs decrease the severity of symptoms, but they have higher discontinuation rates than non-stimulant medications due to their adverse side effects.[46][47] A Cochrane review on the treatment of ADHD in children with tic disorders such as Tourette syndrome indicated that stimulants in general do not make tics worse, but high doses of dextroamphetamine could exacerbate tics in some individuals.[48]
Enhancing performance
Cognitive performance
In 2015, a
task saliency (motivation to perform a task) and increase arousal (wakefulness), in turn promoting goal-directed behavior.[40][53][54] Stimulants such as amphetamine can improve performance on difficult and boring tasks and are used by some students as a study and test-taking aid.[40][54][55] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily used for enhancement of academic performance rather than as recreational drugs.[56][57][58] However, high amphetamine doses that are above the therapeutic range can interfere with working memory and other aspects of cognitive control.[40][54]
Physical performance
Amphetamine is used by some athletes for its psychological and
release of dopamine in the central nervous system.[63][64][65] Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch", allowing the core temperature limit to increase in order to access a reserve capacity that is normally off-limits.[64][66][67] At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance;[59][63] however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature.[68][63]
Recreational
Dextroamphetamine is also used recreationally as a euphoriant and aphrodisiac, and like other
positive reinforcement and positively-valenced emotions, particularly ones involving pleasure.[72] Large recreational doses of dextroamphetamine may produce symptoms of dextroamphetamine overdose.[71] 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.[71] 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).[73][74]
The reason for using crushed
drug dependence, resulting in withdrawal symptoms when drug use stops.[71]
Contraindications
According to the
Raynaud's phenomenon, seizures, thyroid problems, tics, or Tourette syndrome should monitor their symptoms while taking amphetamine.[68][78] 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.[78] Amphetamine has also been shown to pass into breast milk, so the IPCS and the USFDA advise mothers to avoid breastfeeding when using it.[68][78] Due to the potential for reversible growth impairments,[note 6] the USFDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical.[68]
Adverse effects
Physical
tics (a type of movement disorder), and weight loss.[sources 1] Dangerous physical side effects are rare at typical pharmaceutical doses.[60]
Amphetamine stimulates the
smooth muscle of the tract is relaxed.[60] Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opioids.[5][60]
USFDA-commissioned studies from 2011 indicate that in children, young adults, and adults there is no association between serious adverse cardiovascular events (
contraindicated in individuals with cardiovascular disease.[sources 3]
Psychological
At normal therapeutic doses, the most common psychological side effects of amphetamine include increased
Amphetamine psychosis (e.g., delusions and paranoia) can occur in heavy users.[68][90][91] Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy.[68][91][92] According to the USFDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility.[68]
Amphetamine has also been shown to produce a conditioned place preference in humans taking therapeutic doses,[46][93] meaning that individuals acquire a preference for spending time in places where they have previously used amphetamine.[93][94]
Reinforcement disorders
Addiction
| Addiction and dependence glossary[94][95][96] | |
|---|---|
| |
| Transcription factor glossary | |
|---|---|
| |
Signaling cascade in the nucleus accumbens that results in amphetamine addiction |
Biomolecular mechanisms
Chronic use of amphetamine at excessive doses causes alterations in
substituted amphetamines, among others.[sources 6]
induce the expression of ΔFosB (i.e., they cause the brain to produce more of it), chronic acquisition of these rewards can result in a similar pathological state of addiction.[110][109] Consequently, ΔFosB is the most significant factor involved in both amphetamine addiction and amphetamine-induced sexual addictions, which are compulsive sexual behaviors that result from excessive sexual activity and amphetamine use.[110][124][125] These sexual addictions are associated with a dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs.[110][123]
The effects of amphetamine on gene regulation are both dose- and route-dependent.[115] Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses.[115] 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.[115] This suggests that medical use of amphetamine does not significantly affect gene regulation.[115]
Pharmacological treatments
As of December 2019,[update] there is no effective
monotherapy for amphetamine addiction.[107]
A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in
Behavioral treatments
A 2018 systematic review and
psychodynamic therapy, and other combination therapies involving these.[132]
Additionally, research on the
immunoreactivity in the striatum or other parts of the reward system.[112]
| Form of neuroplasticity or behavioral plasticity |
Type of reinforcer | Sources | |||||
|---|---|---|---|---|---|---|---|
| Opiates | Psychostimulants | High fat or sugar food | Sexual intercourse | Physical exercise (aerobic) |
Environmental enrichment | ||
MSNs
|
↑ | ↑ | ↑ | ↑ | ↑ | ↑ | [110] |
| Behavioral plasticity | |||||||
| Escalation of intake | Yes | Yes | Yes | [110] | |||
| Psychostimulant cross-sensitization |
Yes | Not applicable | Yes | Yes | Attenuated | Attenuated | [110] |
| Psychostimulant self-administration |
↑ | ↑ | ↓ | ↓ | ↓ | [110] | |
| Psychostimulant conditioned place preference |
↑ | ↑ | ↓ | ↑ | ↓ | ↑ | [110] |
Reinstatement of drug-seeking behavior
|
↑ | ↑ | ↓ | ↓ | [110] | ||
| Neurochemical plasticity | |||||||
CREB phosphorylation in the nucleus accumbens |
↓ | ↓ | ↓ | ↓ | ↓ | [110] | |
| Sensitized dopamine response in the nucleus accumbens |
No | Yes | No | Yes | [110] | ||
| Altered striatal dopamine signaling | ↓ DRD3 |
↑ DRD3 |
↑ DRD3 |
↑ DRD2 |
↑ DRD2 |
[110] | |
| Altered striatal opioid signaling | No change or ↑μ-opioid receptors |
↑μ-opioid receptors ↑κ-opioid receptors |
↑μ-opioid receptors | ↑μ-opioid receptors | No change | No change | [110] |
| Changes in striatal opioid peptides | ↑dynorphin No change: enkephalin |
↑dynorphin | ↓enkephalin | ↑dynorphin | ↑dynorphin | [110] | |
| Mesocorticolimbic synaptic plasticity | |||||||
| Number of dendrites in the nucleus accumbens | ↓ | ↑ | ↑ | [110] | |||
| Dendritic spine density in the nucleus accumbens |
↓ | ↑ | ↑ | [110] | |||
Dependence and withdrawal
Drug tolerance develops rapidly in amphetamine abuse (i.e., recreational amphetamine use), so periods of extended abuse require increasingly larger doses of the drug in order to achieve the same effect.[134][135] According to a Cochrane review on
increased appetite, increased movement or decreased movement, lack of motivation, sleeplessness or sleepiness, and lucid dreams.[136] The review indicated that the severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence.[136] Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose.[5]
Overdose
An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care.
| System | Minor or moderate overdose[68][60][78] | Severe overdose[sources 8] |
|---|---|---|
Cardiovascular
|
|
|
| Central nervous system |
|
|
Musculoskeletal
|
| |
| Respiratory |
|
|
Urinary
|
|
|
| Other |
|
|
Toxicity
In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic
core body temperature ≥ 40 °C) is necessary for the development of amphetamine-induced neurotoxicity.[142] Prolonged elevations of brain temperature above 40 °C likely promote the development of amphetamine-induced neurotoxicity in laboratory animals by facilitating the production of reactive oxygen species, disrupting cellular protein function, and transiently increasing blood–brain barrier permeability.[142]
Psychosis
An amphetamine overdose can result in a stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia.[90][91] A Cochrane review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely.[90][147] According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis.[90] Psychosis rarely arises from therapeutic use.[68][91][92]
Interactions
Many types of substances are known to
Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of ADHD.[note 12][153]
Pharmacology
Pharmacodynamics
Amphetamine and its enantiomers have been identified as potent
VMAT2, the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.[30]
Dextroamphetamine (the
levorotary enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary.[160][162] Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine.[160] Consequently, dextroamphetamine produces roughly three to four times more central nervous system (CNS) stimulation than levoamphetamine;[160][162] however, levoamphetamine has slightly greater cardiovascular and peripheral effects.[162]
Related endogenous compounds
Amphetamine has a very similar structure and function to the
aromatic amino acid decarboxylase (AADC) enzyme, which converts L-DOPA into dopamine as well.[163][165] In turn, N-methylphenethylamine is metabolized from phenethylamine by phenylethanolamine N-methyltransferase, the same enzyme that metabolizes norepinephrine into epinephrine.[163][165] Like amphetamine, both phenethylamine and N-methylphenethylamine regulate monoamine neurotransmission via TAAR1;[29][164][165] unlike amphetamine, both of these substances are broken down by monoamine oxidase B, and therefore have a shorter half-life than amphetamine.[163][165]
Pharmacokinetics
The oral
plasma proteins.[14] Following absorption, amphetamine readily distributes into most tissues in the body, with high concentrations occurring in cerebrospinal fluid and brain tissue.[21]
The half-lives of amphetamine enantiomers differ and vary with urine pH.[19] At normal urine pH, the half-lives of dextroamphetamine and levoamphetamine are 9–11 hours and 11–14 hours, respectively.[19] Highly acidic urine will reduce the enantiomer half-lives to 7 hours;[21] highly alkaline urine will increase the half-lives up to 34 hours.[21] The immediate-release and extended release variants of salts of both isomers reach peak plasma concentrations at 3 hours and 7 hours post-dose respectively.[19] Amphetamine is eliminated via the kidneys, with 30–40% of the drug being excreted unchanged at normal urinary pH.[19] When the urinary pH is basic, amphetamine is in its free base form, so less is excreted.[19] When urine pH is abnormal, the urinary recovery of amphetamine may range from a low of 1% to a high of 75%, depending mostly upon whether urine is too basic or acidic, respectively.[19] Following oral administration, amphetamine appears in urine within 3 hours.[21] Roughly 90% of ingested amphetamine is eliminated 3 days after the last oral dose.[21]
sympathomimetics are 4-hydroxyamphetamine,[167] 4-hydroxynorephedrine,[168] and norephedrine.[169] The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination.[19][170]
The known metabolic pathways, detectable metabolites, and metabolizing enzymes in humans include the following:
Metabolic pathways of amphetamine in humans[sources 10]
 |
History, society, and culture
Benzedrine inhaler for use as a bronchodilator. Notably, the amphetamine contained in the Benzedrine inhaler was the liquid free-base,[note 14]
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.attention disorders.[10] In Canada indications once included epilepsy and parkinsonism.[180] Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and amobarbital (a barbiturate) sold under the tradename Dexamyl and, in the 1950s, an extended release capsule (the "Spansule").[181] Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue.[182]
It quickly became apparent that dextroamphetamine and other amphetamines had a high potential for
Northern Soul
scene in the north of England to the end of the 1970s.
In October 2010,
GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).[185]
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".[186][187][188] 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.[187]
Formulations
| Brand name |
United States Adopted Name |
(D:L) ratio | Dosage form |
Marketing start date |
Sources |
|---|---|---|---|---|---|
| Adderall | Mixed amphetamine salts | 3:1 (salts) | tablet | 1996 | [27][197] |
| Adderall XR | Mixed amphetamine salts | 3:1 (salts) | capsule | 2001 | [27][197] |
| Mydayis | Mixed amphetamine salts | 3:1 (salts) | capsule | 2017 | [198] |
| Adzenys XR-ODT | amphetamine | 3:1 (base) | ODT | 2016 | [199][200] |
| Dyanavel XR | amphetamine | 3.2:1 (base) | suspension | 2015 | [82][201] |
| Evekeo | amphetamine sulfate | 1:1 (salts) | tablet | 2012 | [77] [202] |
| Dexedrine | dextroamphetamine sulfate | 1:0 (salts) | capsule | 1976 | [27][197] |
| Zenzedi | dextroamphetamine sulfate | 1:0 (salts) | tablet | 2013 | [197] |
| Vyvanse | lisdexamfetamine dimesylate | 1:0 (prodrug) | capsule | 2007 | [27][203] |
| tablet | |||||
| Xelstrym | dextroamphetamine | 1:0 (base) | patch | 2022 | [11] |
Transdermal Dextroamphetamine Patches
Dextroamphetamine is available as a transdermal patch containing dextroamphetamine base under the brand name Xelstrym.[11]
Dextroamphetamine sulfate
In the United States,
controlled-release (CR) capsule preparation in strengths of 5 mg, 10 mg, and 15 mg under the brand name Dexedrine Spansule, with generic versions marketed by Barr and Mallinckrodt. A bubblegum flavored oral solution is available under the brand name ProCentra, manufactured by FSC Pediatrics, which is designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL contains 5 mg dextroamphetamine.[205] The conversion rate between dextroamphetamine sulfate to amphetamine free base is .728.[206]
In Australia, dexamfetamine is available in bottles of 100 instant release 5 mg tablets as a generic drug[207] or slow release dextroamphetamine preparations may be compounded by individual chemists.[208] In the United Kingdom, it is available in 5 mg instant release sulfate tablets under the generic name dexamfetamine sulfate as well as 10 mg and 20 mg strength tablets under the brand name Amfexa. It is also available in generic dexamfetamine sulfate 5 mg/ml oral sugar-free syrup.[209] The brand name Dexedrine was available in the United Kingdom prior to UCB Pharma disinvesting the product to another pharmaceutical company (Auden Mckenzie).[210]
Lisdexamfetamine
Dextroamphetamine is the active
Vyvanse (Elvanse in the European market) (Venvanse in the Brazil market) (lisdexamfetamine dimesylate). 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.[211][212] Vyvanse is marketed as once-a-day dosing as it provides a slow release of dextroamphetamine into the body. Vyvanse is available as capsules, and chewable tablets, and in seven strengths; 10 mg, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg. The conversion rate between lisdexamfetamine dimesylate (Vyvanse) to dextroamphetamine base is 29.5%.[213][214][215]
Adderall
Another pharmaceutical that contains dextroamphetamine is commonly known by the brand name Adderall.[148][149] It is available as immediate release (IR) tablets and extended release (XR) capsules.[148][149] Adderall contains equal amounts of four amphetamine salts:[148][149]
- One-quarter racemic (d,l-)amphetamine aspartate monohydrate
- One-quarter dextroamphetamine saccharate
- One-quarter dextroamphetamine sulfate
- One-quarter racemic (d,l-)amphetamine sulfate
Adderall has a total amphetamine base equivalence of 63%.[148][149] While the enantiomer ratio by dextroamphetamine salts to levoamphetamine salts is 3:1, the amphetamine base content is 75.9% dextroamphetamine, 24.1% levoamphetamine. [note 16]
| drug | formula | molar mass [note 17] |
amphetamine base [note 18] |
amphetamine base in equal doses |
doses with equal base content [note 19] | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| (g/mol) | (percent) | (30 mg dose) | ||||||||
| total | base | total | dextro- | levo- | dextro- | levo- | ||||
| dextroamphetamine sulfate[217][218] | (C9H13N)2•H2SO4 | 368.49
|
270.41
|
73.38%
|
73.38%
|
—
|
22.0 mg
|
—
|
30.0 mg
| |
| amphetamine sulfate[219] | (C9H13N)2•H2SO4 | 368.49
|
270.41
|
73.38%
|
36.69%
|
36.69%
|
11.0 mg
|
11.0 mg
|
30.0 mg
| |
| Adderall | 62.57%
|
47.49%
|
15.08%
|
14.2 mg
|
4.5 mg
|
35.2 mg
| ||||
| 25% | dextroamphetamine sulfate[217][218] | (C9H13N)2•H2SO4 | 368.49
|
270.41
|
73.38%
|
73.38%
|
—
|
|||
| 25% | amphetamine sulfate[219] | (C9H13N)2•H2SO4 | 368.49
|
270.41
|
73.38%
|
36.69%
|
36.69%
|
|||
| 25% | dextroamphetamine saccharate[220] | (C9H13N)2•C6H10O8 | 480.55
|
270.41
|
56.27%
|
56.27%
|
—
|
|||
| 25% | amphetamine aspartate monohydrate[221] | (C9H13N)•C4H7NO4•H2O | 286.32
|
135.21
|
47.22%
|
23.61%
|
23.61%
|
|||
lisdexamfetamine dimesylate[203]
|
C15H25N3O•(CH4O3S)2 | 455.49
|
135.21
|
29.68%
|
29.68%
|
—
|
8.9 mg
|
—
|
74.2 mg
| |
| amphetamine base suspension[82] | C9H13N | 135.21
|
135.21
|
100%
|
76.19%
|
23.81%
|
22.9 mg
|
7.1 mg
|
22.0 mg
| |
Notes
- ^ a b Enantiomers are molecules that are mirror images of one another; they are structurally identical, but of the opposite orientation.[28]
- grade point average, achievement test scores, length of education, and education level), self-esteem (e.g., self-esteem questionnaire assessments, number of suicide attempts, and suicide rates), and social function (e.g., peer nomination scores, social skills, and quality of peer, family, and romantic relationships).[38]
Long-term combination therapy for ADHD (i.e., treatment with both a stimulant and behavioral therapy) produces even larger effect sizes for outcome improvements and improves a larger proportion of outcomes across each domain compared to long-term stimulant therapy alone.[38] - ^ Cochrane reviews are high quality meta-analytic systematic reviews of randomized controlled trials.[45]
- ^ The statements supported by the USFDA come from prescribing information, which is the copyrighted intellectual property of the manufacturer and approved by the USFDA. USFDA contraindications are not necessarily intended to limit medical practice but limit claims by pharmaceutical companies.[76]
- ^ According to one review, amphetamine can be prescribed to individuals with a history of abuse provided that appropriate medication controls are employed, such as requiring daily pick-ups of the medication from the prescribing physician.[27]
- ^ In individuals who experience sub-normal height and weight gains, a rebound to normal levels is expected to occur if stimulant therapy is briefly interrupted.[36][37][81] The average reduction in final adult height from 3 years of continuous stimulant therapy is 2 cm.[81]
- ^ Transcription factors are proteins that increase or decrease the expression of specific genes.[116]
- ^ In simpler terms, this necessary and sufficient relationship means that ΔFosB overexpression in the nucleus accumbens and addiction-related behavioral and neural adaptations always occur together and never occur alone.
- ^ The review indicated that magnesium L-aspartate and magnesium chloride produce significant changes in addictive behavior;[107] other forms of magnesium were not mentioned.
- ^ The 95% confidence interval indicates that there is a 95% probability that the true number of deaths lies between 3,425 and 4,145.
- dopamine efflux in vitro.[150][151][152] The human serotonin transporter and norepinephrine transporter do not contain zinc binding sites.[152]
- ^ 4-Hydroxyamphetamine has been shown to be metabolized into 4-hydroxynorephedrine by dopamine beta-hydroxylase (DBH) in vitro and it is presumed to be metabolized similarly in vivo.[171][174] Evidence from studies that measured the effect of serum DBH concentrations on 4-hydroxyamphetamine metabolism in humans suggests that a different enzyme may mediate the conversion of 4-hydroxyamphetamine to 4-hydroxynorephedrine;[174][176] however, other evidence from animal studies suggests that this reaction is catalyzed by DBH in synaptic vesicles within noradrenergic neurons in the brain.[177][178]
- ^ Free-base form amphetamine is a volatile oil, hence the efficacy of the inhalers.
- ^ 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;[189][190] Dexedrine listed here represents the extended release "Spansule" capsule which was approved in 1976.[191][192] Amphetamine sulfate tablets, now sold as Evekeo (brand), were originally sold as Benzedrine (brand) sulfate in 1935[193][194] and discontinued sometime after 1982.[195][196]
- ^ 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.
- ^ For uniformity, molar masses were calculated using the Lenntech Molecular Weight Calculator[216] and were within 0.01 g/mol of published pharmaceutical values.
- ^ Amphetamine base percentage = molecular massbase / molecular masstotal. Amphetamine base percentage for Adderall = sum of component percentages / 4.
- ^ dose = (1 / amphetamine base percentage) × scaling factor = (molecular masstotal / molecular massbase) × scaling factor. The values in this column were scaled to a 30 mg dose of dextroamphetamine sulfate. Due to pharmacological differences between these medications (e.g., differences in the release, absorption, conversion, concentration, differing effects of enantiomers, half-life, etc.), the listed values should not be considered equipotent doses.
- Image legend
- G proteins & linked receptors(Text color) Transcription factors
Reference notes
References
- ^ PMID 18295156.
- ^ PMID 21042924.
- ^ S2CID 31114829.
- ^ S2CID 207580823.
- ^ ISBN 9781108228749. Retrieved 5 August 2017.
- FDA. Retrieved 22 October 2023.
- ^ "Therapeutic Goods (Poisons Standard—February 2023) Instrument 2022". Australian Government Federal Register of Legislation. 26 September 2022. Retrieved 9 January 2023.
- ^ Fuller K (20 February 2022). "ADHD Stimulant Prescribing Regulations & Authorities in Australia & New Zealand". AADPA. Retrieved 9 January 2023.
- ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
- ^ a b c d "Dexedrine spansule- dextroamphetamine sulfate capsule, extended release". DailyMed. 10 January 2022. Retrieved 28 March 2022.
- ^ a b c "Xelstrym- dextroamphetamine patch, extended release". DailyMed. 6 January 2023. Retrieved 21 January 2023.
- ^ "List of nationally authorised medicinal products : Active substance(s): dexamfetamine : Procedure No. PSUSA/00000986/202109" (PDF). Ema.europa.eu. Retrieved 5 June 2022.
- ^ ISBN 978-3-030-92391-4.
Amphetamine is usually consumed via inhalation or orally, either in the form of a racemic mixture (levoamphetamine and dextroamphetamine) or dextroamphetamine alone (Childress et al. 2019). In general, all amphetamines have high bioavailability when consumed orally, and in the specific case of amphetamine, 90% of the consumed dose is absorbed in the gastrointestinal tract, with no significant differences in the rate and extent of absorption between the two enantiomers (Carvalho et al. 2012; Childress et al. 2019). The onset of action occurs approximately 30 to 45 minutes after consumption, depending on the ingested dose and on the degree of purity or on the concomitant consumption of certain foods (European Monitoring Centre for Drugs and Drug Addiction 2021a; Steingard et al. 2019). It is described that those substances that promote acidification of the gastrointestinal tract cause a decrease in amphetamine absorption, while gastrointestinal alkalinization may be related to an increase in the compound's absorption (Markowitz and Patrick 2017).
- ^ a b Wishart DS, Djombou Feunang Y, Guo AC, Lo EJ, Marcu A, Grant JR, et al. "Amphetamine | DrugBank Online". DrugBank. 5.0.
- ISBN 978-0-7817-2008-3.|quote = Table 21.2 Medications for ADHD ... D-amphetamine ... Onset: 30 min.
- ^ "Dexedrine, ProCentra(dextroamphetamine) dosing, indications, interactions, adverse effects, and more". reference.medscape.com. Retrieved 4 October 2015.
Onset of action: 1–1.5 hr
- ^ ISBN 978-1-4419-1396-8.
Table 9.2 Dextroamphetamine formulations of stimulant medication
Dexedrine [Peak:2–3 h] [Duration:5–6 h] ...
Adderall [Peak:2–3 h] [Duration:5–7 h]
Dexedrine spansules [Peak:7–8 h] [Duration:12 h] ...
Adderall XR [Peak:7–8 h] [Duration:12 h]
Vyvanse [Peak:3–4 h] [Duration:12 h] - S2CID 31791162.
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. ... MAS-XR, and LDX have a long duration of action at 12 hours postdose
- ^ a b c d e f g h i j k l m n o p q "Adderall XR Prescribing Information" (PDF). United States Food and Drug Administration. Shire US Inc. December 2013. pp. 12–13. Retrieved 30 December 2013.
- ^ "Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet". DailyMed. 27 February 2022. Retrieved 21 January 2023.
- ^ a b c d e f "Metabolism/Pharmacokinetics". Amphetamine. Hazardous Substances Data Bank. United States National Library of Medicine – Toxicology Data Network. Archived from the original on 2 October 2017. Retrieved 2 October 2017.
Duration of effect varies depending on agent and urine pH. Excretion is enhanced in more acidic urine. Half-life is 7 to 34 hours and is, in part, dependent on urine pH (half-life is longer with alkaline urine). ... Amphetamines are distributed into most body tissues with high concentrations occurring in the brain and CSF. Amphetamine appears in the urine within about 3 hours following oral administration. ... Three days after a dose of (+ or -)-amphetamine, human subjects had excreted 91% of the (14)C in the urine
- ^ PMID 23065655.
- ISBN 978-1-108-22874-9. Retrieved 8 August 2017.
- ^ "dextrostat (dextroamphetamine sulfate) tablet [Shire US Inc.]". DailyMed. Wayne, PA: Shire US Inc. August 2006. Retrieved 8 November 2013.
- ISBN 978-1-60913-345-0.
Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.
- ^
- ^ PMID 23539642.
- ^ PMID 21073468.
- ^ PMID 21272013.
- ^ S2CID 2873101.
- PMID 18991959.
- ^ PMID 23247506.
- ^ PMID 24107764.
- ^ S2CID 25954331.
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.
- ^ S2CID 3449435.
Several other studies,[97-101] including a meta-analytic review[98] and a retrospective study,[97] suggested that stimulant therapy in childhood is associated with a reduced risk of subsequent substance use, cigarette smoking and alcohol use disorders. ... Recent studies have demonstrated that stimulants, along with the non-stimulants atomoxetine and extended-release guanfacine, are continuously effective for more than 2-year treatment periods with few and tolerable adverse effects. The effectiveness of long-term therapy includes not only the core symptoms of ADHD, but also improved quality of life and academic achievements. The most concerning short-term adverse effects of stimulants, such as elevated blood pressure and heart rate, waned in long-term follow-up studies. ... The current data do not support the potential impact of stimulants on the worsening or development of tics or substance abuse into adulthood. In the longest follow-up study (of more than 10 years), lifetime stimulant treatment for ADHD was effective and protective against the development of adverse psychiatric disorders.
- ^ ISBN 9781441913968.
Ongoing research has provided answers to many of the parents' concerns, and has confirmed the effectiveness and safety of the long-term use of medication.
- ^ PMID 25714373.
The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes.
Figure 3: Treatment benefit by treatment type and outcome group - ^ ISBN 9780071481274.
- ^ ISBN 9780071481274.
Therapeutic (relatively low) doses of psychostimulants, such as methylphenidate and amphetamine, improve performance on working memory tasks both in normal subjects and those with ADHD. ... 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. ...
Beyond these general permissive effects, dopamine (acting via D1 receptors) and norepinephrine (acting at several receptors) can, at optimal levels, enhance working memory and aspects of attention. - PMID 21596055.
- PMID 24082796.
Only one paper53 examining outcomes beyond 36 months met the review criteria. ... There is high level evidence suggesting that pharmacological treatment can have a major beneficial effect on the core symptoms of ADHD (hyperactivity, inattention, and impulsivity) in approximately 80% of cases compared with placebo controls, in the short term.
- ISBN 9781441913968.
- ^ "Stimulants for Attention Deficit Hyperactivity Disorder". WebMD. Healthwise. 12 April 2010. Retrieved 12 November 2013.
- S2CID 29410060.
- ^ PMID 30091808.
- PMID 26844979.
- PMID 29944175.
- ^ PMID 25499957.
The procognitive actions of psychostimulants are only associated with low doses. Surprisingly, despite nearly 80 years of clinical use, the neurobiology of the procognitive actions of psychostimulants has only recently been systematically investigated. Findings from this research unambiguously demonstrate that the cognition-enhancing effects of psychostimulants involve the preferential elevation of catecholamines in the PFC and the subsequent activation of norepinephrine α2 and dopamine D1 receptors. ... This differential modulation of PFC-dependent processes across dose appears to be associated with the differential involvement of noradrenergic α2 versus α1 receptors. Collectively, this evidence indicates that at low, clinically relevant doses, psychostimulants are devoid of the behavioral and neurochemical actions that define this class of drugs and instead act largely as cognitive enhancers (improving PFC-dependent function). ... In particular, in both animals and humans, lower doses maximally improve performance in tests of working memory and response inhibition, whereas maximal suppression of overt behavior and facilitation of attentional processes occurs at higher doses.
- S2CID 15788121.
Specifically, in a set of experiments limited to high-quality designs, we found significant enhancement of several cognitive abilities. ... The results of this meta-analysis ... do confirm the reality of cognitive enhancing effects for normal healthy adults in general, while also indicating that these effects are modest in size.
- PMID 24749160.
Amphetamine has been shown to improve consolidation of information (0.02 ≥ P ≤ 0.05), leading to improved recall.
- PMID 11337538.
- ISBN 9780071481274.
Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.
- ^ PMID 24344115.
- ^ 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.
- PMID 16999660.
- PMID 25228824.
misuse of prescription stimulants has become a serious problem on college campuses across the US and has been recently documented in other countries as well. ... Indeed, large numbers of students claim to have engaged in the nonmedical use of prescription stimulants, which is reflected in lifetime prevalence rates of prescription stimulant misuse ranging from 5% to nearly 34% of students.
- S2CID 207580823.
Overall, the data suggest that ADHD medication misuse and diversion are common health care problems for stimulant medications, with the prevalence believed to be approximately 5% to 10% of high school students and 5% to 35% of college students, depending on the study.
- ^ 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 - ^ ISBN 9780071624428.
- ^ Bracken NM (January 2012). "National Study of Substance Use Trends Among NCAA College Student-Athletes" (PDF). NCAA Publications. National Collegiate Athletic Association. Archived (PDF) from the original on 9 October 2022. Retrieved 8 October 2013.
- PMID 18500382.
- ^ PMID 21658550.
In 1980, Chandler and Blair47 showed significant increases in knee extension strength, acceleration, anaerobic capacity, time to exhaustion during exercise, pre-exercise and maximum heart rates, and time to exhaustion during maximal oxygen consumption (VO2 max) testing after administration of 15 mg of dextroamphetamine versus placebo. Most of the information to answer this question has been obtained in the past decade through studies of fatigue rather than an attempt to systematically investigate the effect of ADHD drugs on exercise.
- ^ S2CID 30392999.
In high-ambient temperatures, dopaminergic manipulations clearly improve performance. The distribution of the power output reveals that after dopamine reuptake inhibition, subjects are able to maintain a higher power output compared with placebo. ... Dopaminergic drugs appear to override a safety switch and allow athletes to use a reserve capacity that is 'off-limits' in a normal (placebo) situation.
- PMID 24198770.
Manipulations of dopaminergic signaling profoundly influence interval timing, leading to the hypothesis that dopamine influences internal pacemaker, or "clock," activity. For instance, amphetamine, which increases concentrations of dopamine at the synaptic cleft advances the start of responding during interval timing, whereas antagonists of D2 type dopamine receptors typically slow timing;... Depletion of dopamine in healthy volunteers impairs timing, while amphetamine releases synaptic dopamine and speeds up timing.
- PMID 25852568.
Aside from accounting for the reduced performance of mentally fatigued participants, this model rationalizes the reduced RPE and hence improved cycling time trial performance of athletes using a glucose mouthwash (Chambers et al., 2009) and the greater power output during a RPE matched cycling time trial following amphetamine ingestion (Swart, 2009). ... Dopamine stimulating drugs are known to enhance aspects of exercise performance (Roelands et al., 2008)
- S2CID 22782401.
This indicates that subjects did not feel they were producing more power and consequently more heat. The authors concluded that the "safety switch" or the mechanisms existing in the body to prevent harmful effects are overridden by the drug administration (Roelands et al., 2008b). Taken together, these data indicate strong ergogenic effects of an increased DA concentration in the brain, without any change in the perception of effort.
- ^ a b c d e f g h i j k l m n o p q r s t u v w "Adderall XR- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate capsule, extended release". DailyMed. Shire US Inc. 17 July 2019. Retrieved 22 December 2019.
- ^ "Commonly Abused Prescription Drugs Chart". National Institute on Drug Abuse. Retrieved 7 May 2012.
- ^ "Stimulant ADHD Medications – Methylphenidate and Amphetamines". National Institute on Drug Abuse. Archived from the original on 2 May 2012. Retrieved 7 May 2012.
- ^ a b c d e "National Institute on Drug Abuse. 2009. Stimulant ADHD Medications – Methylphenidate and Amphetamines". National Institute on Drug Abuse. Retrieved 27 February 2013.
- PMID 26109341.
Rewards in operant conditioning are positive reinforcers. ... 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. ... Rewards are attractive. They are motivating and make us exert an effort. ... Rewards induce approach behavior, also called appetitive or preparatory behavior, sexual behavior, and consummatory behavior. ... Thus any stimulus, object, event, activity, or situation that has the potential to make us approach and consume it is by definition a reward. ... Rewarding stimuli, objects, events, situations, and activities consist of several major components. First, rewards have basic sensory components (visual, auditory, somatosensory, gustatory, and olfactory) ... 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) ... 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. ... 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. ... 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. ... 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.
- ^ Canadian ADHD Practice Guidelines (PDF) (Fourth ed.). Canadian ADHD Resource Alliance. 2018. p. 67. Archived from the original (PDF) on 2 May 2023. Retrieved 2 May 2023.
- PMID 18596945.
- PMID 22129527.
- S2CID 12798818.
statements on package inserts are not intended to limit medical practice. Rather they are intended to limit claims by pharmaceutical companies. ... the FDA asserts explicitly, and the courts have upheld that clinical decisions are to be made by physicians and patients in individual situations.
- ^ a b c d "Evekeo- amphetamine sulfate tablet". DailyMed. Arbor Pharmaceuticals, LLC. 14 August 2019. Retrieved 22 December 2019.
- ^ a b c d e f g h i j k Heedes G, Ailakis J. "Amphetamine (PIM 934)". INCHEM. International Programme on Chemical Safety. Retrieved 24 June 2014.
- PMID 15554766.
- PMID 24972362.
- ^ PMID 18295156.
- PMID 16784007. Retrieved 29 April 2015.
Table 2. Decongestants Causing Rhinitis Medicamentosa
– Nasal decongestants:
– Sympathomimetic:
• Amphetamine - ^ a b "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. 1 November 2011. Archived from the original on 25 August 2019. Retrieved 24 December 2019.
- PMID 22043968.
- ^ a b "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. 12 December 2011. Archived from the original on 14 December 2019. Retrieved 24 December 2013.
- PMID 22161946.
- PMID 19727285.
- ^ O'Connor PG (February 2012). "Amphetamines". Merck Manual for Health Care Professionals. Merck. Retrieved 8 May 2012.
- ^ 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.
psychotic symptoms of individuals with amphetamine psychosis may be due exclusively to heavy use of the drug or heavy use of the drug may exacerbate an underlying vulnerability to schizophrenia. - ^ PMID 23216941.
In these studies, amphetamine was given in consecutively higher doses until psychosis was precipitated, often after 100–300 mg of amphetamine ... Secondly, psychosis has been viewed as an adverse event, although rare, in children with ADHD who have been treated with amphetamine
- ^ a b Greydanus D. "Stimulant Misuse: Strategies to Manage a Growing Problem" (PDF). American College Health Association (Review Article). ACHA Professional Development Program. p. 20. Archived from the original (PDF) on 3 November 2013. Retrieved 2 November 2013.
- ^ PMID 19111278.
This study demonstrates that humans, like nonhumans, prefer a place associated with amphetamine administration. These findings support the idea that subjective responses to a drug contribute to its ability to establish place conditioning.
- ^ ISBN 9780071481274.
- ^ PMID 24459410.
Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
- PMID 26816013.
Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder. - ^ PMID 19877494.
[Psychostimulants] increase cAMP levels in striatum, which activates protein kinase A (PKA) and leads to phosphorylation of its targets. This includes the cAMP response element binding protein (CREB), the phosphorylation of which induces its association with the histone acetyltransferase, CREB binding protein (CBP) to acetylate histones and facilitate gene activation. This is known to occur on many genes including fosB and c-fos in response to psychostimulant exposure. ΔFosB is also upregulated by chronic psychostimulant treatments, and is known to activate certain genes (eg, cdk5) and repress others (eg, c-fos) where it recruits HDAC1 as a corepressor. ... Chronic exposure to psychostimulants increases glutamatergic [signaling] from the prefrontal cortex to the NAc. Glutamatergic signaling elevates Ca2+ levels in NAc postsynaptic elements where it activates CaMK (calcium/calmodulin protein kinases) signaling, which, in addition to phosphorylating CREB, also phosphorylates HDAC5.
Figure 2: Psychostimulant-induced signaling events - PMID 22200950.
Coincident and convergent input often induces plasticity on a postsynaptic neuron. The NAc integrates processed information about the environment from basolateral amygdala, hippocampus, and prefrontal cortex (PFC), as well as projections from midbrain dopamine neurons. Previous studies have demonstrated how dopamine modulates this integrative process. For example, high frequency stimulation potentiates hippocampal inputs to the NAc while simultaneously depressing PFC synapses (Goto and Grace, 2005). The converse was also shown to be true; stimulation at PFC potentiates PFC–NAc synapses but depresses hippocampal–NAc synapses. In light of the new functional evidence of midbrain dopamine/glutamate co-transmission (references above), new experiments of NAc function will have to test whether midbrain glutamatergic inputs bias or filter either limbic or cortical inputs to guide goal-directed behavior.
- ^ Kanehisa Laboratories (10 October 2014). "Amphetamine – Homo sapiens (human)". KEGG Pathway. Retrieved 31 October 2014.
Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), projection areas of mesocorticolimbic DA neurons and key components of the "brain reward circuit". Amphetamine achieves this elevation in extracellular levels of DA by promoting efflux from synaptic terminals. ... Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain.
- PMID 24939695.
- ^ PMID 21989194.
ΔFosB serves as one of the master control proteins governing this structural plasticity. ... ΔFosB also represses G9a expression, leading to reduced repressive histone methylation at the cdk5 gene. The net result is gene activation and increased CDK5 expression. ... In contrast, ΔFosB binds to the c-fos gene and recruits several co-repressors, including HDAC1 (histone deacetylase 1) and SIRT 1 (sirtuin 1). ... The net result is c-fos gene repression.
Figure 4: Epigenetic basis of drug regulation of gene expression - ^ PMID 23430970.
The 35-37 kD ΔFosB isoforms accumulate with chronic drug exposure due to their extraordinarily long half-lives. ... As a result of its stability, the ΔFosB protein persists in neurons for at least several weeks after cessation of drug exposure. ... ΔFosB overexpression in nucleus accumbens induces NFκB ... In contrast, the ability of ΔFosB to repress the c-Fos gene occurs in concert with the recruitment of a histone deacetylase and presumably several other repressive proteins such as a repressive histone methyltransferase
- PMID 18640924.
Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch—from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure
- ISBN 9780071827706.
Such agents also have important therapeutic uses; cocaine, for example, is used as a local anesthetic (Chapter 2), and amphetamines and methylphenidate are used in low doses to treat attention deficit hyperactivity disorder and in higher doses to treat narcolepsy (Chapter 12). Despite their clinical uses, these drugs are strongly reinforcing, and their long-term use at high doses is linked with potential addiction, especially when they are rapidly administered or when high-potency forms are given.
- S2CID 71267668.
When oral formulations of psychostimulants are used at recommended doses and frequencies, they are unlikely to yield effects consistent with abuse potential in patients with ADHD.
- ^ Kanehisa Laboratories (10 October 2014). "Amphetamine – Homo sapiens (human)". KEGG Pathway. Retrieved 31 October 2014.
- ^ PMID 18557129.)
{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link - ^ S2CID 19157711.
ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure.
- ^ 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. ... ΔFosB serves as one of the master control proteins governing this structural plasticity.
- ^ PMID 21459101.
Similar to environmental enrichment, studies have found that exercise reduces self-administration and relapse to drugs of abuse (Cosgrove et al., 2002; Zlebnik et al., 2010). There is also some evidence that these preclinical findings translate to human populations, as exercise reduces withdrawal symptoms and relapse in abstinent smokers (Daniel et al., 2006; Prochaska et al., 2008), and one drug recovery program has seen success in participants that train for and compete in a marathon as part of the program (Butler, 2005). ... In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al., 2006; Aiken, 2007; Lader, 2008).
- ^ PMID 23806439.
These findings suggest that exercise may "magnitude"-dependently prevent the development of an addicted phenotype possibly by blocking/reversing behavioral and neuroadaptive changes that develop during and following extended access to the drug. ... Exercise has been proposed as a treatment for drug addiction that may reduce drug craving and risk of relapse. Although few clinical studies have investigated the efficacy of exercise for preventing relapse, the few studies that have been conducted generally report a reduction in drug craving and better treatment outcomes ... Taken together, these data suggest that the potential benefits of exercise during relapse, particularly for relapse to psychostimulants, may be mediated via chromatin remodeling and possibly lead to greater treatment outcomes.
- ^ PMID 26182835.
Collectively, these findings demonstrate that exercise may serve as a substitute or competition for drug abuse by changing ΔFosB or cFos immunoreactivity in the reward system to protect against later or previous drug use. ... The postulate that exercise serves as an ideal intervention for drug addiction has been widely recognized and used in human and animal rehabilitation.
- ^ PMID 25397661.
The limited research conducted suggests that exercise may be an effective adjunctive treatment for SUDs. In contrast to the scarce intervention trials to date, a relative abundance of literature on the theoretical and practical reasons supporting the investigation of this topic has been published. ... numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects.
- S2CID 15139406. Archived from the original(PDF) on 19 September 2018.
- ^ PMID 23085425.
- ISBN 9780071481274.
- ^ Kanehisa Laboratories (29 October 2014). "Alcoholism – Homo sapiens (human)". KEGG Pathway. Retrieved 31 October 2014.
- PMID 19202072.
- ^ PMID 23643695.
- ^ PMID 23020045.
- PMID 23475113.
- S2CID 11513288.
- ^ PMID 22641964.
It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. ... these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.
- PMID 23426671.
- S2CID 25317397.
- ISBN 9780071827706.
Pharmacologic treatment for psychostimulant addiction is generally unsatisfactory. As previously discussed, cessation of cocaine use and the use of other psychostimulants in dependent individuals does not produce a physical withdrawal syndrome but may produce dysphoria, anhedonia, and an intense desire to reinitiate drug use.
- ^ S2CID 198136436.
- PMID 24716825.
Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved.
- ^ PMID 26644139.
When considered together with the rapidly growing literature in the field a compelling case emerges in support of developing TAAR1-selective agonists as medications for preventing relapse to psychostimulant abuse.
- ^ PMID 26092759.
Existing data provided robust preclinical evidence supporting the development of TAAR1 agonists as potential treatment for psychostimulant abuse and addiction.
- ^ ISBN 9780071481274.
- ^ PMID 26903885.
Physical Exercise
There is accelerating evidence that physical exercise is a useful treatment for preventing and reducing drug addiction ... In some individuals, exercise has its own rewarding effects, and a behavioral economic interaction may occur, such that physical and social rewards of exercise can substitute for the rewarding effects of drug abuse. ... The value of this form of treatment for drug addiction in laboratory animals and humans is that exercise, if it can substitute for the rewarding effects of drugs, could be self-maintained over an extended period of time. Work to date in [laboratory animals and humans] regarding exercise as a treatment for drug addiction supports this hypothesis. ... Animal and human research on physical exercise as a treatment for stimulant addiction indicates that this is one of the most promising treatments on the horizon. - PMID 23996457.
- ^ "Amphetamines: Drug Use and Abuse". Merck Manual Home Edition. Merck. February 2003. Archived from the original on 17 February 2007. Retrieved 28 February 2007.
- ^ 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) ... The severity of withdrawal symptoms is greater in amphetamine dependent individuals who are older and who have more extensive amphetamine use disorders (McGregor 2005). 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) ...
- ^ S2CID 40931380.
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.
- PMID 25530442.
Amphetamine use disorders ... 3,788 (3,425–4,145)
- S2CID 20755466.
- ISBN 9780071668330.
- S2CID 7582744.
- ^ PMID 27626044.
Hyperthermia alone does not produce amphetamine-like neurotoxicity but AMPH and METH exposures that do not produce hyperthermia (≥40 °C) are minimally neurotoxic. Hyperthermia likely enhances AMPH and METH neurotoxicity directly through disruption of protein function, ion channels and enhanced ROS production. ... The hyperthermia and the hypertension produced by high doses amphetamines are a primary cause of transient breakdowns in the blood-brain barrier (BBB) resulting in concomitant regional neurodegeneration and neuroinflammation in laboratory animals. ... In animal models that evaluate the neurotoxicity of AMPH and METH, it is quite clear that hyperthermia is one of the essential components necessary for the production of histological signs of dopamine terminal damage and neurodegeneration in cortex, striatum, thalamus and hippocampus.
- ^ "Amphetamine". United States National Library of Medicine – Toxicology Data Network. Hazardous Substances Data Bank. Archived from the original on 2 October 2017. Retrieved 2 October 2017.
Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.
- ISBN 9780071481274.
Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.
- S2CID 21892355.
- PMID 18596830.
- ISBN 9780195030570.
- ^ a b c d e f g h i j "Adderall- dextroamphetamine saccharate, amphetamine aspartate, dextroamphetamine sulfate, and amphetamine sulfate tablet". DailyMed. 27 February 2022. Retrieved 28 March 2022.
- ^ a b c d e f g h i j "Adderall XR- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine sulfate and amphetamine aspartate capsule, extended release". DailyMed. 3 March 2022. Retrieved 28 March 2022.
- S2CID 24589993.
Zinc binds at ... 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.
- PMID 21338876.
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).
- ^ PMID 11940571.
- PMID 23021477.
- PMID 27141430.
Despite the challenges in determining synaptic vesicle pH, the proton gradient across the vesicle membrane is of fundamental importance for its function. Exposure of isolated catecholamine vesicles to protonophores collapses the pH gradient and rapidly redistributes transmitter from inside to outside the vesicle. ... Amphetamine and its derivatives like methamphetamine are weak base compounds that are the only widely used class of drugs known to elicit transmitter release by a non-exocytic mechanism. As substrates for both DAT and VMAT, amphetamines can be taken up to the cytosol and then sequestered in vesicles, where they act to collapse the vesicular pH gradient.
- PMID 21772817.
Three important new aspects of TAs action have recently emerged: (a) inhibition of firing due to increased release of dopamine; (b) reduction of D2 and GABAB receptor-mediated inhibitory responses (excitatory effects due to disinhibition); and (c) a direct TA1 receptor-mediated activation of GIRK channels which produce cell membrane hyperpolarization.
- ^ "TAAR1". GenAtlas. University of Paris. 28 January 2012. Retrieved 29 May 2014.
• tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of dopamine (DA) neurons of the ventral tegmental area (VTA)
- PMID 25033183.
AMPH also increases intracellular calcium (Gnegy et al., 2004) that is associated with calmodulin/CamKII activation (Wei et al., 2007) and modulation and trafficking of the DAT (Fog et al., 2006; Sakrikar et al., 2012). ... For example, AMPH increases extracellular glutamate in various brain regions including the striatum, VTA and NAc (Del Arco et al., 1999; Kim et al., 1981; Mora and Porras, 1993; Xue et al., 1996), but it has not been established whether this change can be explained by increased synaptic release or by reduced clearance of glutamate. ... DHK-sensitive, EAAT2 uptake was not altered by AMPH (Figure 1A). The remaining glutamate transport in these midbrain cultures is likely mediated by EAAT3 and this component was significantly decreased by AMPH
- PMID 23968642.
AMPH and METH also stimulate DA efflux, which is thought to be a crucial element in their addictive properties [80], although the mechanisms do not appear to be identical for each drug [81]. These processes are PKCβ– and CaMK–dependent [72, 82], and PKCβ knock-out mice display decreased AMPH-induced efflux that correlates with reduced AMPH-induced locomotion [72].
- ^ S2CID 14140873.
- ^ PMID 22037049.
- PMID 11459929.
- ^ ISBN 978-0-07-162442-8.
- ^ PMID 19948186.
- ^ PMID 27424325.
- ^ PMID 15860375.
- ^ PMID 12191709.
- ^ "Compound Summary". p-Hydroxyamphetamine. PubChem Compound Database. United States National Library of Medicine – National Center for Biotechnology Information. Retrieved 15 October 2013.
- ^ "Compound Summary". p-Hydroxynorephedrine. PubChem Compound Database. United States National Library of Medicine – National Center for Biotechnology Information. Retrieved 15 October 2013.
- ^ "Compound Summary". Phenylpropanolamine. PubChem Compound Database. United States National Library of Medicine – National Center for Biotechnology Information. Retrieved 15 October 2013.
- ^ "Pharmacology and Biochemistry". Amphetamine. Pubchem Compound Database. United States National Library of Medicine – National Center for Biotechnology Information. Retrieved 12 October 2013.
- ^ ISBN 9781609133450.
The simplest unsubstituted phenylisopropylamine, 1-phenyl-2-aminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class (39). ... The phase 1 metabolism of amphetamine analogs is catalyzed by two systems: cytochrome P450 and flavin monooxygenase. ... Amphetamine can also undergo aromatic hydroxylation to p-hydroxyamphetamine. ... Subsequent oxidation at the benzylic position by DA β-hydroxylase affords p-hydroxynorephedrine. Alternatively, direct oxidation of amphetamine by DA β-hydroxylase can afford norephedrine.
- PMID 4809526. Retrieved 6 November 2014.
Dopamine-β-hydroxylase catalyzed the removal of the pro-R hydrogen atom and the production of 1-norephedrine, (2S,1R)-2-amino-1-hydroxyl-1-phenylpropane, from d-amphetamine.
- PMID 10027866.
- ^ PMID 13977820.
Hydroxyamphetamine was administered orally to five human subjects ... Since conversion of hydroxyamphetamine to hydroxynorephedrine occurs in vitro by the action of dopamine-β-oxidase, a simple method is suggested for measuring the activity of this enzyme and the effect of its inhibitors in man. ... The lack of effect of administration of neomycin to one patient indicates that the hydroxylation occurs in body tissues. ... a major portion of the β-hydroxylation of hydroxyamphetamine occurs in non-adrenal tissue. Unfortunately, at the present time one cannot be completely certain that the hydroxylation of hydroxyamphetamine in vivo is accomplished by the same enzyme which converts dopamine to noradrenaline.
- ^ S2CID 23738007.
Figure 1. Glycine conjugation of benzoic acid. The glycine conjugation pathway consists of two steps. First benzoate is ligated to CoASH to form the high-energy benzoyl-CoA thioester. This reaction is catalyzed by the HXM-A and HXM-B medium-chain acid:CoA ligases and requires energy in the form of ATP. ... The benzoyl-CoA is then conjugated to glycine by GLYAT to form hippuric acid, releasing CoASH. In addition to the factors listed in the boxes, the levels of ATP, CoASH, and glycine may influence the overall rate of the glycine conjugation pathway.
- S2CID 28641000.
The biologic significance of the different levels of serum DβH activity was studied in two ways. First, in vivo ability to β-hydroxylate the synthetic substrate hydroxyamphetamine was compared in two subjects with low serum DβH activity and two subjects with average activity. ... In one study, hydroxyamphetamine (Paredrine), a synthetic substrate for DβH, was administered to subjects with either low or average levels of serum DβH activity. The percent of the drug hydroxylated to hydroxynorephedrine was comparable in all subjects (6.5-9.62) (Table 3).
- PMID 4457764.
In species where aromatic hydroxylation of amphetamine is the major metabolic pathway, p-hydroxyamphetamine (POH) and p-hydroxynorephedrine (PHN) may contribute to the pharmacological profile of the parent drug. ... The location of the p-hydroxylation and β-hydroxylation reactions is important in species where aromatic hydroxylation of amphetamine is the predominant pathway of metabolism. Following systemic administration of amphetamine to rats, POH has been found in urine and in plasma.
The observed lack of a significant accumulation of PHN in brain following the intraventricular administration of (+)-amphetamine and the formation of appreciable amounts of PHN from (+)-POH in brain tissue in vivo supports the view that the aromatic hydroxylation of amphetamine following its systemic administration occurs predominantly in the periphery, and that POH is then transported through the blood-brain barrier, taken up by noradrenergic neurones in brain where (+)-POH is converted in the storage vesicles by dopamine β-hydroxylase to PHN. - PMID 2600821.
The metabolism of p-OHA to p-OHNor is well documented and dopamine-β hydroxylase present in noradrenergic neurons could easily convert p-OHA to p-OHNor after intraventricular administration.
- ^ "Dexedrine". Medic8. Archived from the original on 19 December 2009. Retrieved 27 November 2013.
- ^ "Dextroamphetamine [monograph]". Internet Mental Health. Archived from the original on 27 April 2006. Retrieved 6 September 2015.
- ^ "Information on Dexedrine: A Quick Review | Weitz & Luxenberg". Weitzlux.com. 31 August 2013. Retrieved 5 January 2017.
- PMID 23539642.
- ^ King DG (4 January 2017). "Prescription Forgery". Handwriting Services International. Archived from the original on 5 July 2008.
- ISBN 978-0-8155-1144-1.
- ^ "Dexedrine FAQs". Archived from the original on 17 June 2011.
- ^ Bonné J (9 January 2003). "'Go pills': A war on drugs?". NBC News. Retrieved 5 January 2017.
- ^ a b Woodring JC. "Air Force scientists battle aviator fatigue". Archived from the original on 14 October 2012. Retrieved 5 January 2017.
- PMID 7661838.
- PMID 23539642.
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.
- ^ "Drugs@FDA: Dexedrine". U.S. Food and Drug Administration (FDA). Retrieved 28 March 2022.
- ^ "Drugs@FDA: Dexedrine". U.S. Food and Drug Administration (FDA). Retrieved 28 March 2022.
- ^ "Drugs@FDA: Dexedrine: Label and Approval History". U.S. Food and Drug Administration (FDA). Archived from the original on 28 August 2021. Retrieved 30 December 2015.
08/02/1976 ... Approval
- PMID 21451781.
Bradley experimented with Benzedrine sulfate, a drug marketed to doctors by the company Smith, Kline & French (SKF) between 1935 and 1937...
- PMID 23539642.
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.
- PMID 23539642.
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...
- ^ "FDA Approved Drug Products: Label and Approval History (Benzedrine)". U.S. Food and Drug Administration (FDA). Retrieved 11 March 2016.
Action Date 5/11/1982, Supplement Number 007, Approval Type Chemistry
- ^ a b c d "National Drug Code Amphetamine Search Results". National Drug Code Directory. U.S. Food and Drug Administration (FDA). Archived from the original on 16 December 2013. Retrieved 16 December 2013.
- ^ "Mydayis- dextroamphetamine sulfate, dextroamphetamine saccharate, amphetamine aspartate monohydrate, and amphetamine sulfate capsule, extended release". DailyMed. 28 October 2022. Retrieved 21 January 2023.
- ^ "Adzenys XR-ODT- amphetamine tablet, orally disintegrating". DailyMed. 10 March 2022. Retrieved 21 January 2023.
- ^ "Drug Approval Package: Adzenys XR-ODT (amphetamine)". U.S. Food and Drug Administration (FDA). 27 January 2016. Retrieved 21 January 2023.
- ^ "Evekeo". U.S. Food and Drug Administration (FDA). Retrieved 11 August 2015.
- ^ a b "Vyvanse Prescribing Information" (PDF). United States Food and Drug Administration. Shire US Inc. May 2017. pp. 17–21. Retrieved 10 July 2017.
- ^ "Zenzedi (dextroamphetamine sulfate, USP)". Zenzedi.com. Retrieved 5 January 2017.
- ^ "ProCentra (dextroamphetamine sulfate 5 mg/5 mL Oral Solution)". FSC Laboratories. Archived from the original on 5 October 2010.
- ^ US 7655630, Mickle T, Krishnan S, Bishop B, Lauderback C, Moncrief JS, Oberlender R, Piccariello T, Paul BJ, Verbicky CD, "Abuse-resistant amphetamine prodrugs", issued 2010, assigned to Takeda Pharmaceutical Co Ltd
- .
- ^ "Pharmaceutical Services". .health.nsw.gov.au. Archived from the original on 5 May 2013. Retrieved 5 January 2017.
- ^ "Dexamfetamine sulphate - Medicinal forms". British National Formulary. BMJ Group and Pharmaceutical Press (Royal Pharmaceutical Society). Retrieved 9 November 2019.
- ^ "Dexamfetamine – Prescribe Generically" (PDF). Red/Amber News (22). Interface Pharmacist Network Specialist Medicines (IPNSM): 2. November 2010. Archived from the original (PDF) on 18 May 2013. Retrieved 20 April 2012.
- S2CID 37893582.
- ^ Elayan I (2006). "NRP-104 (lisdexamphetamine dimesylate)" (PDF). Pharmacology/Toxicology Review and Evaluation. U.S. Food and Drug Administration. pp. 18–19.
- PMID 22009816. Retrieved 12 March 2014.
- S2CID 25343254.
- S2CID 29702399.
- ^ "Molecular Weight Calculator". Lenntech. Retrieved 19 August 2015.
- ^ a b "Dextroamphetamine Sulfate USP". Mallinckrodt Pharmaceuticals. March 2014. Retrieved 19 August 2015.
- ^ a b "D-amphetamine sulfate". Tocris. 2015. Retrieved 19 August 2015.
- ^ a b "Amphetamine Sulfate USP". Mallinckrodt Pharmaceuticals. March 2014. Retrieved 19 August 2015.
- ^ "Dextroamphetamine Saccharate". Mallinckrodt Pharmaceuticals. March 2014. Retrieved 19 August 2015.
- ^ "Amphetamine Aspartate". Mallinckrodt Pharmaceuticals. March 2014. Retrieved 19 August 2015.
External links
Wikimedia Commons has media related to Dextroamphetamine.
- "PIM 178: Dexamphetamine Sulphate)". Poison Information Monograph. International Programme on Chemical Safety (IPCS) Chemical Safety Information from Intergovernmental organizations (INCHEM).
| Main articles and pharmaceuticals |
| ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Neuropharmacology |
| ||||||||
| Active metabolites | |||||||||
| Related articles |
| ||||||||
