Dextroamphetamine
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Dextroamphetamine is a central nervous system (CNS) stimulant and enantiomer of amphetamine that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy.[6][23] It is also used illicitly to enhance cognitive and athletic performance, and recreationally as an aphrodisiac and euphoriant. Dextroamphetamine is generally regarded as the prototypical stimulant.
The amphetamine molecule exists as two enantiomers, levoamphetamine and dextroamphetamine. Dextroamphetamine is the dextrorotatory, or 'right-handed', enantiomer and exhibits more pronounced effects on the central nervous system than levoamphetamine. Pharmaceutical dextroamphetamine sulfate is available as both a brand name and generic drug in a variety of dosage forms. Dextroamphetamine is sometimes prescribed as the inactive prodrug lisdexamfetamine.
Side effects of dextroamphetamine at therapeutic doses include elevated mood, decreased appetite, dry mouth, bruxism, headache, increased heart rate, increased wakefulness or insomnia, anxiety, and irritability, among others.[24] At excessive doses, psychosis (i.e., hallucinations, delusions), addiction, and rapid muscle breakdown may occur. However, for individuals with pre-existing psychotic disorders, there may be a risk of psychosis even at therapeutic doses.[25]
Dextroamphetamine, like other amphetamines, elicits its stimulating effects via several distinct actions: it inhibits or reverses the transporter proteins for the monoamine neurotransmitters (namely the serotonin, norepinephrine and dopamine transporters) either via trace amine-associated receptor 1 (TAAR1) or in a TAAR1 independent fashion when there are high cytosolic concentrations of the monoamine neurotransmitters[26] and it releases these neurotransmitters from synaptic vesicles via vesicular monoamine transporter 2 (VMAT2).[27] It also shares many chemical and pharmacological properties with human trace amines, particularly phenethylamine and N-methylphenethylamine, the latter being an isomer of amphetamine produced within the human body. It is available as a generic medication.[24] In 2023, mixed amphetamine salts (Adderall) was the 15th most commonly prescribed medication in the United States, with more than 32 million prescriptions.[28][29]
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Uses
Medical

Dextroamphetamine is used to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy,[6] and is sometimes prescribed off-label for depression and obesity.[23]
ADHD
{{#lsth:Amphetamine|ADHD}}
Narcolepsy
{{#lsth:Amphetamine|Narcolepsy}}
Enhancing performance
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{{#section-h:Amphetamine|Enhancing performance}}
Recreational
Dextroamphetamine is also used recreationally as a euphoriant and aphrodisiac, and, like other amphetamines, is used as a club drug for its energetic and euphoric high. Dextroamphetamine is considered to have a high potential for misuse in a recreational manner since individuals typically report feeling euphoric, more alert, and more energetic after taking the drug.[30][31][32] Dextroamphetamine's dopaminergic (rewarding) properties affect the mesocorticolimbic circuit; a group of neural structures responsible for incentive salience (i.e., "wanting"; desire or craving for a reward and motivation), positive reinforcement and positively-valenced emotions, particularly ones involving pleasure.[33] Large recreational doses of dextroamphetamine may produce dextroamphetamine overdose.[32] 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.[32] 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).[34][35]
The reason for using crushed spansules for insufflation and injection methods is evidently due to the instant-release forms of the drug seen in tablet preparations often containing a sizable amount of inactive binders and fillers alongside the active d-amphetamine, such as dextrose.[36] Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels.[32] Chronic overuse of dextroamphetamine can lead to severe drug dependence, resulting in withdrawal symptoms when drug use stops.[32]
Contraindications
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{{#section-h:Amphetamine|Contraindications}}
Adverse effects
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{{#section-h:Amphetamine|Adverse effects}}
Overdose
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{{#section-h:Amphetamine|Overdose}}
Interactions
Many types of substances are known to interact with amphetamine, resulting in altered drug action or metabolism of amphetamine, the interacting substance, or both.[15][37][25] Inhibitors of the enzymes that metabolize amphetamine (e.g., CYP2D6 and FMO3) will prolong its elimination half-life, meaning that its effects will last longer.[22][37][25] Amphetamine also interacts with MAOIs, particularly monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase plasma catecholamines (i.e., norepinephrine and dopamine);[37][25] therefore, concurrent use of both is dangerous.[37][25] Amphetamine modulates the activity of most psychoactive drugs. In particular, amphetamine may decrease the effects of sedatives and depressants and increase the effects of stimulants and antidepressants.[37][25] Amphetamine may also decrease the effects of antihypertensives and antipsychotics due to its effects on blood pressure and dopamine respectively.[37][25] Zinc supplementation may reduce the minimum effective dose of amphetamine when it is used for the treatment of ADHD.[note 1][41] Norepinephrine reuptake inhibitors (NRIs) like atomoxetine prevent norepinephrine release induced by amphetamines and have been found to reduce the stimulant, euphoriant, and sympathomimetic effects of dextroamphetamine in humans.[42][43][44]
Pharmacology
Pharmacodynamics
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| Compound | NE | DA | 5-HT | Ref | ||
|---|---|---|---|---|---|---|
| Phenethylamine | 10.9 | 39.5 | >10,000 | [45][46][47] | ||
| Dextroamphetamine | 6.6–7.2 | 5.8–24.8 | 698–1,765 | [48][49] | ||
| Levoamphetamine | 9.5 | 27.7 | ND | [46][47] | ||
| Dextromethamphetamine | 12.3–13.8 | 8.5–24.5 | 736–1,292 | [48][50] | ||
| Levomethamphetamine | 28.5 | 416 | 4,640 | [48] | ||
| Notes: The smaller the value, the more strongly the drug releases the neurotransmitter. See also Monoamine releasing agent § Activity profiles for a larger table with more compounds. Refs:[51][52] | ||||||
Pharmacodynamics of amphetamine in a dopamine neuron
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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.[59][60] 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).[26][59][61] Amphetamine enantiomers are also substrates for a specific neuronal synaptic vesicle uptake transporter called VMAT2.[27] When amphetamine is taken up by VMAT2, the vesicle releases (effluxes) dopamine, norepinephrine, and serotonin, among other monoamines, into the cytosol in exchange.[27]
Dextroamphetamine (the dextrorotary enantiomer) and levoamphetamine (the levorotary enantiomer) have identical pharmacodynamics, but their binding affinities to their biomolecular targets vary.[60][62] Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine.[60] Consequently, dextroamphetamine produces roughly three to four times more central nervous system (CNS) stimulation than levoamphetamine;[60][62] however, levoamphetamine has slightly greater cardiovascular and peripheral effects.[62]
Related endogenous compounds
{{#section-h:Amphetamine|Related endogenous compounds}}
Pharmacokinetics
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{{#section-h:Amphetamine|Pharmacokinetics}}
History, society, and culture
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Racemic amphetamine was first synthesized under the chemical name "phenylisopropylamine" in Berlin, 1887 by the Romanian chemist Lazăr Edeleanu. It was not widely marketed until 1932, when the pharmaceutical company Smith, Kline & French (now known as 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 2] not a chloride or sulfate salt.
In 1935, the medical community became aware of the stimulant properties of amphetamine, specifically the dextroamphetamine isomer, and in 1937 Smith, Kline, and French introduced tablets under the brand name Dexedrine.[63] In the United States, Dexedrine was approved to treat narcolepsy and attention deficit hyperactivity disorder (ADHD).[6] In Canada indications once included epilepsy and parkinsonism.[64] Dextroamphetamine was marketed in various other forms in the following decades, primarily by Smith, Kline, and French, such as several combination medications including a mixture of dextroamphetamine and amobarbital (a barbiturate) sold under the brand name Dexamyl and, in the 1950s, an extended release capsule (the "Spansule").[65] Preparations containing dextroamphetamine were also used in World War II as a treatment against fatigue.[23]
It quickly became apparent that dextroamphetamine and other amphetamines had a high potential for misuse, although they were not heavily controlled until 1970, when the Comprehensive Drug Abuse Prevention and Control Act was passed by the United States Congress. Dextroamphetamine, along with other sympathomimetics, was eventually classified as Schedule II, the most restrictive category possible for a drug with a government-sanctioned, recognized medical use.[66] 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).[67] It became popular on the mod scene in England in the early 1960s, and carried through to the Northern Soul scene in the north of England to the end of the 1970s.
In October 2010, GlaxoSmithKline sold the rights for Dexedrine Spansule to Amedra Pharmaceuticals (a subsidiary of CorePharma).[68]
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".[69][70][71] The Tarnak Farm incident was linked by media reports to the use of this drug on long term fatigued pilots. The military did not accept this explanation, citing the lack of similar incidents. Newer stimulant medications or awakeness promoting agents with different side effect profiles, such as modafinil, are being investigated and sometimes issued for this reason.[70]
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 | [23][77] |
| Adderall XR | Mixed amphetamine salts | 3:1 (salts) | capsule | 2001 | [23][77] |
| Mydayis | Mixed amphetamine salts | 3:1 (salts) | capsule | 2017 | [78] |
| Adzenys XR-ODT | amphetamine | 3:1 (base) | ODT | 2016 | [79][80] |
| Dyanavel XR | amphetamine | 3.2:1 (base) | suspension | 2015 | [81][82] |
| Evekeo | amphetamine sulfate | 1:1 (salts) | tablet | 2012 | [83] [84] |
| Dexedrine | dextroamphetamine sulfate | 1:0 (salts) | capsule | 1976 | [23][77] |
| Zenzedi | dextroamphetamine sulfate | 1:0 (salts) | tablet | 2013 | [77] |
| Vyvanse | lisdexamfetamine dimesylate | 1:0 (prodrug) | capsule | 2007 | [23][85] |
| tablet | |||||
| Xelstrym | dextroamphetamine | 1:0 (base) | patch | 2022 | [7] |
Transdermal dextroamphetamine patches
Dextroamphetamine is available as a transdermal patch containing dextroamphetamine base under the brand name Xelstrym.[7]
Dextroamphetamine sulfate
In the United States, immediate release (IR) formulations of dextroamphetamine sulfate are available generically as 5 mg and 10 mg tablets, marketed by Barr (Teva Pharmaceutical Industries), Mallinckrodt Pharmaceuticals, Wilshire Pharmaceuticals, Aurobindo Pharmaceutical USA and CorePharma. Previous IR tablets sold under the brand names Dexedrine and Dextrostat have been discontinued but in 2015, IR tablets became available by the brand name Zenzedi, offered as 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg and 30 mg tablets.[86] Dextroamphetamine sulfate is also available as a controlled-release (CR) capsule preparation in strengths of 5 mg, 10 mg, and 15 mg under the brand name Dexedrine Spansule, with generic versions marketed by Barr and Mallinckrodt. A bubblegum flavored oral solution is available under the brand name ProCentra, manufactured by FSC Pediatrics, which is designed to be an easier method of administration in children who have difficulty swallowing tablets, each 5 mL contains 5 mg dextroamphetamine.[87] The conversion rate between dextroamphetamine sulfate to amphetamine free base is .728.[88]
In Australia, dexamfetamine is available in bottles of 100 instant release 5 mg tablets as a generic drug[89] or slow release dextroamphetamine preparations may be compounded by individual chemists.[90] 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.[91] The brand name Dexedrine was available in the United Kingdom prior to UCB Pharma disinvesting the product to another pharmaceutical company, Auden Mckenzie.[92]
Lisdexamfetamine
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Dextroamphetamine is the active metabolite of the prodrug lisdexamfetamine (L-lysine-dextroamphetamine), available by the brand name Vyvanse (Elvanse in the European market and Venvanse in the Brazilian market). Dextroamphetamine is liberated from lisdexamfetamine enzymatically following contact with red blood cells. The conversion is rate-limited by the enzyme, which prevents high blood concentrations of dextroamphetamine and reduces lisdexamfetamine's drug liking and abuse potential at clinical doses.[93][94] 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%.[95][96][97]
Adderall
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Another pharmaceutical that contains dextroamphetamine is commonly known by the brand name Adderall.[37][25] It is available as immediate release (IR) tablets and extended release (XR) capsules.[37][25] Adderall contains equal amounts of four amphetamine salts:[37][25]
- 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%.[37][25] 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 4]
| drug | formula | molar mass [note 5] |
amphetamine base [note 6] |
amphetamine base in equal doses |
doses with equal base content [note 7] | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Page Template:Nobold/styles.css has no content.(g/mol) | Page Template:Nobold/styles.css has no content.(percent) | Page Template:Nobold/styles.css has no content.(30 mg dose) | ||||||||
| total | base | total | dextro- | levo- | dextro- | levo- | ||||
| dextroamphetamine sulfate[99][100] | (C9H13N)2•H2SO4 | 368.49
|
270.41
|
73.38%
|
73.38%
|
—
|
22.0 mg
|
—
|
30.0 mg
| |
| amphetamine sulfate[101] | (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[99][100] | (C9H13N)2•H2SO4 | 368.49
|
270.41
|
73.38%
|
73.38%
|
—
|
|||
| 25% | amphetamine sulfate[101] | (C9H13N)2•H2SO4 | 368.49
|
270.41
|
73.38%
|
36.69%
|
36.69%
|
|||
| 25% | dextroamphetamine saccharate[102] | (C9H13N)2•C6H10O8 | 480.55
|
270.41
|
56.27%
|
56.27%
|
—
|
|||
| 25% | amphetamine aspartate monohydrate[103] | (C9H13N)•C4H7NO4•H2O | 286.32
|
135.21
|
47.22%
|
23.61%
|
23.61%
|
|||
| lisdexamfetamine dimesylate[85] | C15H25N3O•(CH4O3S)2 | 455.49
|
135.21
|
29.68%
|
29.68%
|
—
|
8.9 mg
|
—
|
74.2 mg
| |
| amphetamine base suspension[81] | C9H13N | 135.21
|
135.21
|
100%
|
76.19%
|
23.81%
|
22.9 mg
|
7.1 mg
|
22.0 mg
| |
Research
Schizophrenia
Dextroamphetamine reduces the negative symptoms of schizophrenia, and has been shown to enhance the effects of auditory discrimination training in schizophrenic patients.[104][105][106]
Notes
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- ^ The human dopamine transporter contains a high affinity extracellular zinc binding site which, upon zinc binding, inhibits dopamine reuptake and amplifies amphetamine-induced dopamine efflux in vitro.[38][39][40] The human serotonin transporter and norepinephrine transporter do not contain zinc binding sites.[40]
- ^ 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;[23][72] Dexedrine listed here represents the extended release "Spansule" capsule which was approved in 1976.[73][74] Amphetamine sulfate tablets, now sold as Evekeo (brand), were originally sold as Benzedrine (brand) sulfate in 1935[75][23] and discontinued sometime after 1982.[23][76]
- ^ 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[98] 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
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Reference notes
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References
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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]
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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
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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.
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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.
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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).
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Adjunctive therapy with DL-methylphenidate in atomoxetine partial responders has been successful (Wilens et al. 2009), but this also increases the rates of insomnia, irritability and loss of appetite (Hammerness et al. 2009). This combination therapy has not included amphetamine because blockade of NET by atomoxetine prevents entry of amphetamine into presynaptic noradrenergic terminals (Sofuoglu et al. 2009).
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The active form of the drug has a central nervous system stimulating activity by the primary inhibition of DAT, NET, trace amine-associated receptor 1 (TAAR1) and vesicular monoamine transporter 2 (SLC18A2), among other targets, therefore regulating the reuptake and release of catecholamines (primarily NE and DA) on the synaptic cleft. ...
LDX can also promote the increase of DA in the synaptic cleft by activating protein TAAR1, which produces the efflux of monoamine NTs, mainly DA, from storage sites on presynaptic neurons. TAAR1 activation leads to intracellular cAMP signalling that results in PKA and PKC phosphorylation and activation. This PKC activation decreases DAT1, NET1 and SERT cell surface expression, intensifying the direct blockage of monoamine transporters by LDX and improving the neurotransmission imbalance in ADHD. - ^ Page Module:Citation/CS1/styles.css has no content.Sulzer D, Cragg SJ, Rice ME (August 2016). "Striatal dopamine neurotransmission: regulation of release and uptake". Basal Ganglia. 6 (3): 123–148. doi:10.1016/j.baga.2016.02.001. PMC 4850498. 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.
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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.
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• tonically activates inwardly rectifying K(+) channels, which reduces the basal firing frequency of dopamine (DA) neurons of the ventral tegmental area (VTA)
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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
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External links
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