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120-421: Amphetamine (contracted from a lpha - m ethyl ph en et hyl amine ) is a central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy , and obesity ; it is also used to treat binge eating disorder in the form of its inactive prodrug lisdexamfetamine . Amphetamine was discovered as a chemical in 1887 by Lazăr Edeleanu , and then as

240-617: A dopamine dysregulation syndrome which occurs in some patients taking dopaminergic drugs . The effects of amphetamine on gene regulation are both dose- and route-dependent. Most of the research on gene regulation and addiction is based upon animal studies with intravenous amphetamine administration at very high doses. 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. This suggests that medical use of amphetamine does not significantly affect gene regulation. As of December 2019, there

360-462: A vasovagal response , Raynaud's phenomenon (reduced blood flow to the hands and feet), and tachycardia (increased heart rate). Sexual side effects in males may include erectile dysfunction , frequent erections, or prolonged erections . Gastrointestinal side effects may include abdominal pain , constipation , diarrhea , and nausea . Other potential physical side effects include appetite loss , blurred vision , dry mouth , excessive grinding of

480-429: A compound is a structural isomer that differs from it in the atoms and bonds that are considered to comprise the "skeleton" of the molecule. For organic compounds , such as alkanes , that usually means the carbon atoms and the bonds between them. For example, there are three skeletal isomers of pentane : n -pentane (often called simply "pentane"), isopentane (2-methylbutane) and neopentane (dimethylpropane). If

600-579: A day, which is roughly 100 times the maximum daily therapeutic dose. Symptoms of a moderate and extremely large overdose are listed below; fatal amphetamine poisoning usually also involves convulsions and coma . In 2013, overdose on amphetamine, methamphetamine, and other compounds implicated in an " amphetamine use disorder " resulted in an estimated 3,788 deaths worldwide ( 3,425–4,145  deaths, 95% confidence ). In rodents and primates, sufficiently high doses of amphetamine cause dopaminergic neurotoxicity , or damage to dopamine neurons, which

720-454: A drug in the late 1920s. It exists as two enantiomers : levoamphetamine and dextroamphetamine . Amphetamine properly refers to a specific chemical, the racemic free base , which is equal parts of the two enantiomers in their pure amine forms. The term is frequently used informally to refer to any combination of the enantiomers, or to either of them alone. Historically, it has been used to treat nasal congestion and depression. Amphetamine

840-456: A fuel substrate. Dextroamphetamine also activates TAAR1 in peripheral organs along the gastrointestinal tract that are involved in the regulation of food intake and body weight. Together, these actions confer an anorexigenic effect that promotes satiety in response to feeding and may decrease binge eating as a secondary effect. Medical reviews of randomized controlled trials have demonstrated that lisdexamfetamine, at doses between 50-70 mg,

960-630: A greater effect on cataplexy, a symptom more sensitive to the effects of norepinephrine and serotonin. Noradrenergic and serotonergic nuclei in the ARAS are involved in the regulation of the REM sleep cycle and function as "REM-off" cells, with amphetamine's effect on norepinephrine and serotonin contributing to the suppression of REM sleep and a possible reduction of cataplexy at high doses. The American Academy of Sleep Medicine (AASM) 2021 clinical practice guideline conditionally recommends dextroamphetamine for

1080-408: A hydrogen atom on the β-carbon is a β-hydrogen , and so on. Organic molecules with more than one functional group can be a source of confusion. Generally the functional group responsible for the name or type of the molecule is the 'reference' group for purposes of carbon-atom naming. For example, the molecules nitrostyrene and phenethylamine are quite similar; the former can even be reduced into

1200-412: A molecule can be defined mathematically as a permutation of the atoms that exchanges at least two atoms but does not change the molecule's structure. Two atoms then can be said to be structurally equivalent if there is a structural symmetry that takes one to the other. Thus, for example, all four hydrogen atoms of methane are structurally equivalent, because any permutation of them will preserve all

1320-487: A more favorable pharmacokinetic profile and easy crushability (especially tablets). Injection into the bloodstream can be dangerous because insoluble fillers within the tablets can block small blood vessels. Chronic overuse of dextroamphetamine can lead to severe drug dependence , resulting in withdrawal symptoms when drug use stops. According to the International Programme on Chemical Safety (IPCS) and

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1440-460: 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. 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

1560-408: A preference for spending time in places where they have previously used amphetamine. Addiction is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses; in fact, lifetime stimulant therapy for ADHD that begins during childhood reduces the risk of developing substance use disorders as an adult. Pathological overactivation of

1680-722: A pronounced gene-related phenotype ) in the D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and regulates multiple behavioral effects (e.g., reward sensitization and escalating drug self-administration ) involved in addiction. Once ΔFosB is sufficiently overexpressed, it induces an addictive state that becomes increasingly more severe with further increases in ΔFosB expression. It has been implicated in addictions to alcohol , cannabinoids , cocaine , methylphenidate , nicotine , opioids , phencyclidine , propofol , and substituted amphetamines , among others. ΔJunD ,

1800-459: A protein are about 3.8 ångströms (380 picometers ) apart. The α-carbon is important for enol - and enolate -based carbonyl chemistry as well. Chemical transformations affected by the conversion to either an enolate or an enol, in general, lead to the α-carbon acting as a nucleophile , becoming, for example, alkylated in the presence of primary haloalkane . An exception is in reaction with silyl chlorides , bromides , and iodides , where

1920-403: A reserve capacity that is normally off-limits. At therapeutic doses, the adverse effects of amphetamine do not impede athletic performance; however, at much higher doses, amphetamine can induce effects that severely impair performance, such as rapid muscle breakdown and elevated body temperature . Amphetamine, specifically the more dopaminergic dextrorotatory enantiomer ( dextroamphetamine ),

2040-512: A reward and motivation), positive reinforcement and positively-valenced emotions, particularly ones involving pleasure . Large recreational doses of dextroamphetamine may produce symptoms of dextroamphetamine overdose . 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. Immediate-release formulations have higher potential for abuse via insufflation (snorting) or intravenous injection due to

2160-597: A stimulant psychosis that may involve a variety of symptoms, such as delusions and paranoia. A Cochrane review on treatment for amphetamine, dextroamphetamine, and methamphetamine psychosis states that about 5–15% of users fail to recover completely. According to the same review, there is at least one trial that shows antipsychotic medications effectively resolve the symptoms of acute amphetamine psychosis. Psychosis rarely arises from therapeutic use. Many types of substances are known to interact with amphetamine, resulting in altered drug action or metabolism of amphetamine,

2280-500: A task) and increase arousal (wakefulness), in turn promoting goal-directed behavior. 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. 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. However, high amphetamine doses that are above

2400-561: A time-limited withdrawal syndrome that occurs within 24 hours of their last dose." This review noted that withdrawal symptoms in chronic, high-dose users are frequent, occurring in roughly 88% of cases, and persist for 3–4  weeks with a marked "crash" phase occurring during the first week. Amphetamine withdrawal symptoms can include anxiety, drug craving , depressed mood , fatigue , increased appetite , increased movement or decreased movement , lack of motivation, sleeplessness or sleepiness, and lucid dreams . The review indicated that

2520-506: A transcription factor, and G9a , a histone methyltransferase enzyme, both oppose the function of ΔFosB and inhibit increases in its expression. Sufficiently overexpressing ΔJunD in the nucleus accumbens with viral vectors can completely block many of the neural and behavioral alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB). Similarly, accumbal G9a hyperexpression results in markedly increased histone 3 lysine residue 9 dimethylation ( H3K9me2 ) and blocks

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2640-453: Is a serious risk with heavy recreational amphetamine use, but is unlikely to occur from long-term medical use at therapeutic doses. Very high doses can result in psychosis (e.g., hallucinations , delusions and paranoia ) which rarely occurs at therapeutic doses even during long-term use. Recreational doses are generally much larger than prescribed therapeutic doses and carry a far greater risk of serious side effects. Amphetamine belongs to

2760-410: Is also used as an athletic performance enhancer and cognitive enhancer , and recreationally as an aphrodisiac and euphoriant . It is a prescription drug in many countries, and unauthorized possession and distribution of amphetamine are often tightly controlled due to the significant health risks associated with recreational use. The first amphetamine pharmaceutical was Benzedrine , a brand which

2880-421: 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 (d-amphetamine) 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. A notable part of the 1960s mod subculture in

3000-467: Is characterized by dopamine terminal degeneration and reduced transporter and receptor function. There is no evidence that amphetamine is directly neurotoxic in humans. However, large doses of amphetamine may indirectly cause dopaminergic neurotoxicity as a result of hyperpyrexia , the excessive formation of reactive oxygen species , and increased autoxidation of dopamine. Animal models of neurotoxicity from high-dose amphetamine exposure indicate that

3120-401: Is characterized by recurrent and persistent episodes of compulsive binge eating. These episodes are often accompanied by marked distress and a feeling of loss of control over eating. The pathophysiology of BED is not fully understood, but it is believed to involve dysfunctional dopaminergic reward circuitry along the cortico-striatal-thalamic-cortical loop . As of July 2024, lisdexamfetamine is

3240-409: Is dangerous. 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 . Amphetamine may also decrease the effects of antihypertensives and antipsychotics due to its effects on blood pressure and dopamine respectively. Zinc supplementation may reduce

3360-504: 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 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. One review highlighted

3480-417: Is high, amphetamine may reduce gastrointestinal motility (the rate at which content moves through the digestive system); however, amphetamine may increase motility when the smooth muscle of the tract is relaxed. Amphetamine also has a slight analgesic effect and can enhance the pain relieving effects of opioids . FDA-commissioned studies from 2011 indicate that in children, young adults, and adults there

3600-453: Is known to produce abnormal dopamine system development or nerve damage, but, in humans with ADHD, long-term use of pharmaceutical amphetamines at therapeutic doses appears to improve brain development and nerve growth. 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

3720-592: Is known to strongly induce cocaine- and amphetamine-regulated transcript (CART) gene expression , a neuropeptide involved in feeding behavior, stress, and reward, which induces observable increases in neuronal development and survival in vitro . The CART receptor has yet to be identified, but there is significant evidence that CART binds to a unique G i /G o -coupled GPCR . Amphetamine also inhibits monoamine oxidases at very high doses, resulting in less monoamine and trace amine metabolism and consequently higher concentrations of synaptic monoamines. In humans,

Amphetamine - Misplaced Pages Continue

3840-415: Is located. In this example, the carbon atoms are numbered from one to five, which starts at one end and proceeds sequentially along the chain. Now the position of the oxygen atom can be defined as on carbon atom number two, three or four. However, atoms two and four are exactly equivalent - which can be shown by turning the molecule around by 180 degrees. The locant is the number of the carbon atom to which

3960-774: Is no association between serious adverse cardiovascular events ( sudden death , heart attack , and stroke ) and the medical use of amphetamine or other ADHD stimulants. However, amphetamine pharmaceuticals are contraindicated in individuals with cardiovascular disease . At normal therapeutic doses, the most common psychological side effects of amphetamine include increased alertness , apprehension, concentration , initiative, self-confidence and sociability, mood swings ( elated mood followed by mildly depressed mood ), insomnia or wakefulness , and decreased sense of fatigue. Less common side effects include anxiety , change in libido , grandiosity , irritability , repetitive or obsessive behaviors, and restlessness; these effects depend on

4080-482: Is no effective pharmacotherapy for amphetamine addiction. Reviews from 2015 and 2016 indicated that TAAR1 -selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions; however, as of February 2016, the only compounds which are known to function as TAAR1-selective agonists are experimental drugs . Amphetamine addiction is largely mediated through increased activation of dopamine receptors and co-localized NMDA receptors in

4200-563: Is no equivalence between these two equivalence classes . Structural equivalences between atoms of a parent molecule reduce the number of positional isomers that can be obtained by replacing those atoms for a different element or group. Thus, for example, the structural equivalence between the six hydrogens of ethane C 2 H 6 means that there is just one structural isomer of ethanol C 2 H 5 OH , not 6. The eight hydrogens of propane C 3 H 8 are partitioned into two structural equivalence classes (the six on

4320-452: Is not an effective monotherapy for amphetamine addiction. A systematic review and meta-analysis from 2019 assessed the efficacy of 17 different pharmacotherapies used in randomized controlled trials (RCTs) for amphetamine and methamphetamine addiction; it found only low-strength evidence that methylphenidate might reduce amphetamine or methamphetamine self-administration. There was low- to moderate-strength evidence of no benefit for most of

4440-464: Is safe and effective for the treatment of moderate-to-severe BED in adults. These reviews suggest that lisdexamfetamine is persistently effective at treating BED and is associated with significant reductions in the number of binge eating days and binge eating episodes per week. Furthermore, a meta-analytic systematic review highlighted an open-label, 12-month extension safety and tolerability study that reported lisdexamfetamine remained effective at reducing

4560-579: Is sufficiently overexpressed, it begins to increase the severity of addictive behavior (i.e., compulsive drug-seeking) with further increases in its expression. While there are currently no effective drugs for treating amphetamine addiction, regularly engaging in sustained aerobic exercise appears to reduce the risk of developing such an addiction. Exercise therapy improves clinical treatment outcomes and may be used as an adjunct therapy with behavioral therapies for addiction. Chronic use of amphetamine at excessive doses causes alterations in gene expression in

4680-580: Is the most radical type of isomerism . It is opposed to stereoisomerism , in which the atoms and bonding scheme are the same, but only the relative spatial arrangement of the atoms is different. Examples of the latter are the enantiomers , whose molecules are mirror images of each other, and the cis and trans versions of 2-butene . Among the structural isomers, one can distinguish several classes including skeletal isomers , positional isomers (or regioisomers ), functional isomers , tautomers , and structural isotopomers . A skeletal isomer of

4800-463: Is the pair propanal H 3 C–CH 2 –C(=O)-H and acetone H 3 C–C(=O)–CH 3 : the first has a –C(=O)H functional group, which makes it an aldehyde , whereas the second has a C–C(=O)–C group, that makes it a ketone . Another example is the pair ethanol H 3 C–CH 2 –OH (an alcohol ) and dimethyl ether H 3 C–O–CH 2 H (an ether ). In contrast, 1-propanol and 2-propanol are structural isomers, but not functional isomers, since they have

4920-509: Is thought to phosphorylate SERT via TAAR1 . Like dopamine, amphetamine has low, micromolar affinity at the human 5-HT1A receptor . Acute amphetamine administration in humans increases endogenous opioid release in several brain structures in the reward system . Extracellular levels of glutamate , the primary excitatory neurotransmitter in the brain, have been shown to increase in the striatum following exposure to amphetamine. This increase in extracellular glutamate presumably occurs via

Amphetamine - Misplaced Pages Continue

5040-426: Is usually not noticeable, but when respiration is already compromised, it may be evident. Amphetamine also induces contraction in the urinary bladder sphincter , the muscle which controls urination, which can result in difficulty urinating. This effect can be useful in treating bed wetting and loss of bladder control . The effects of amphetamine on the gastrointestinal tract are unpredictable. If intestinal activity

5160-446: The n -pentane parent molecule can give any of three different position isomers: Another example of regioisomers are α-linolenic and γ-linolenic acids , both octadecatrienoic acids , each of which has three double bonds, but on different positions along the chain. Functional isomers are structural isomers which have different functional groups , resulting in significantly different chemical and physical properties. An example

5280-480: The central nervous system after conversion to its pharmacologically active metabolite, dextroamphetamine. Centrally, dextroamphetamine increases neurotransmitter activity of dopamine and norepinephrine in prefrontal cortical regions that regulate cognitive control of behavior. Similar to its therapeutic effect in ADHD, dextroamphetamine enhances cognitive control and may reduce impulsivity in patients with BED by enhancing

5400-420: The delocalized bonding in the benzene molecule and other aromatic compounds. Depending on the context, one may require that each atom be paired with an atom of the same isotope, not just of the same element. Two molecules then can be said to be structural isomers (or, if isotopes matter, structural isotopomers) if they have the same molecular formula but do not have the same structure. Structural symmetry of

5520-421: The firing rate of dopamine neurons, preventing a hyper-dopaminergic state. Amphetamine is also a substrate for the presynaptic vesicular monoamine transporter , VMAT2 . Following amphetamine uptake at VMAT2, amphetamine induces the collapse of the vesicular pH gradient, which results in the release of dopamine molecules from synaptic vesicles into the cytosol via dopamine efflux through VMAT2. Subsequently,

5640-518: The indirect activation of both dopamine D 1 receptor and α 2 -adrenergic receptor in the prefrontal cortex . A systematic review from 2014 found that low doses of amphetamine also improve memory consolidation , in turn leading to improved recall of information . Therapeutic doses of amphetamine also enhance cortical network efficiency, an effect which mediates improvements in working memory in all individuals. Amphetamine and other ADHD stimulants also improve task saliency (motivation to perform

5760-523: The lateral hypothalamus , leading to significantly reduced cerebrospinal orexin levels; this reduction is a diagnostic biomarker for type 1 narcolepsy. Lateral hypothalamic orexin neurons innervate every component of the ascending reticular activating system (ARAS), which includes noradrenergic , dopaminergic , histaminergic , and serotonergic nuclei that promote wakefulness . Amphetamine’s therapeutic mode of action in narcolepsy primarily involves increasing monoamine neurotransmitter activity in

5880-503: The mesocorticolimbic projection , which arise through transcriptional and epigenetic mechanisms. The most important transcription factors that produce these alterations are Delta FBJ murine osteosarcoma viral oncogene homolog B ( ΔFosB ), cAMP response element binding protein ( CREB ), and nuclear factor-kappa B ( NF-κB ). ΔFosB is the most significant biomolecular mechanism in addiction because ΔFosB overexpression (i.e., an abnormally high level of gene expression which produces

6000-471: The mesolimbic pathway , a dopamine pathway that connects the ventral tegmental area to the nucleus accumbens , plays a central role in amphetamine addiction. Individuals who frequently self-administer high doses of amphetamine have a high risk of developing an amphetamine addiction, since chronic use at high doses gradually increases the level of accumbal ΔFosB , a "molecular switch" and "master control protein" for addiction. Once nucleus accumbens ΔFosB

6120-410: The minimum effective dose of amphetamine when it is used for the treatment of ADHD. In general, there is no significant interaction when consuming amphetamine with food, but the pH of gastrointestinal content and urine affects the absorption and excretion of amphetamine, respectively. Acidic substances reduce the absorption of amphetamine and increase urinary excretion, and alkaline substances do

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6240-500: The neurobiological effects of physical exercise suggests that daily aerobic exercise, especially endurance exercise (e.g., marathon running ), prevents the development of drug addiction and is an effective adjunct therapy (i.e., a supplemental treatment) for amphetamine addiction. Exercise leads to better treatment outcomes when used as an adjunct treatment, particularly for psychostimulant addictions. In particular, aerobic exercise decreases psychostimulant self-administration, reduces

6360-621: The oxygen acts as the nucleophile to produce silyl enol ether . Structural isomer In chemistry , a structural isomer (or constitutional isomer in the IUPAC nomenclature ) of a compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct bonds between them. The term metamer was formerly used for the same concept. For example, butanol H 3 C−(CH 2 ) 3 −OH , methyl propyl ether H 3 C−(CH 2 ) 2 −O−CH 3 , and diethyl ether (H 3 CCH 2 −) 2 O have

6480-456: The phenethylamine class . It is also the parent compound of its own structural class, the substituted amphetamines , which includes prominent substances such as bupropion , cathinone , MDMA , and methamphetamine . As a member of the phenethylamine class, amphetamine is also chemically related to the naturally occurring trace amine neuromodulators, specifically phenethylamine and N -methylphenethylamine , both of which are produced within

6600-496: The prefrontal cortex . Stimulants like methylphenidate and amphetamine are effective in treating ADHD because they increase neurotransmitter activity in these systems. Approximately 80% of those who use these stimulants see improvements in ADHD symptoms. 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. The Cochrane reviews on

6720-603: The presynaptic neuron either through DAT or by diffusing across the neuronal membrane directly. As a consequence of DAT uptake, amphetamine produces competitive reuptake inhibition at the transporter. Upon entering the presynaptic neuron, amphetamine activates TAAR1 which, through protein kinase A (PKA) and protein kinase C (PKC) signaling, causes DAT phosphorylation . Phosphorylation by either protein kinase can result in DAT internalization ( non-competitive reuptake inhibition), but PKC-mediated phosphorylation alone induces

6840-402: The reinstatement (i.e., relapse) of drug-seeking, and induces increased dopamine receptor D 2 (DRD2) density in the striatum . This is the opposite of pathological stimulant use, which induces decreased striatal DRD2 density. One review noted that exercise may also prevent the development of a drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of

6960-426: The reversal of dopamine transport through DAT (i.e., dopamine efflux ). Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through an unidentified Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent pathway, in turn producing dopamine efflux. Through direct activation of G protein-coupled inwardly-rectifying potassium channels , TAAR1 reduces

7080-419: The reward system . 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. According to a Cochrane review on withdrawal in individuals who compulsively use amphetamine and methamphetamine, "when chronic heavy users abruptly discontinue amphetamine use, many report

7200-469: The 1,2-dideutero structural isotopomer would occur as two stereoisotopomers, cis and trans . Two molecules (including polyatomic ions) A and B have the same structure if each atom of A can be paired with an atom of B of the same element, in a one-to-one way, so that for every bond in A there is a bond in B, of the same type, between corresponding atoms; and vice versa. This requirement applies also to complex bonds that involve three or more atoms, such as

7320-523: The ARAS. This includes noradrenergic neurons in the locus coeruleus , dopaminergic neurons in the ventral tegmental area , histaminergic neurons in the tuberomammillary nucleus , and serotonergic neurons in the dorsal raphe nucleus . Dextroamphetamine, the more dopaminergic enantiomer of amphetamine, is particularly effective at promoting wakefulness because dopamine release has the greatest influence on cortical activation and cognitive arousal, relative to other monoamines. In contrast, levoamphetamine may have

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7440-1125: The U.S. Food and Drug Administration (FDA), amphetamine is contraindicated in people with a history of drug abuse , cardiovascular disease , severe agitation , or severe anxiety. It is also contraindicated in individuals with advanced arteriosclerosis (hardening of the arteries), glaucoma (increased eye pressure), hyperthyroidism (excessive production of thyroid hormone), or moderate to severe hypertension . These agencies indicate that people who have experienced allergic reactions to other stimulants or who are taking monoamine oxidase inhibitors (MAOIs) should not take amphetamine, although safe concurrent use of amphetamine and monoamine oxidase inhibitors has been documented. These agencies also state that anyone with anorexia nervosa , bipolar disorder , depression, hypertension, liver or kidney problems, mania , psychosis , Raynaud's phenomenon , seizures , thyroid problems, tics , or Tourette syndrome should monitor their symptoms while taking amphetamine. Evidence from human studies indicates that therapeutic amphetamine use does not cause developmental abnormalities in

7560-486: The UK was recreational amphetamine use, which was used to fuel all-night dances at clubs like Manchester's Twisted Wheel . Newspaper reports described dancers emerging from clubs at 5 a.m. with dilated pupils. Mods used the drug for stimulation and alertness , which they viewed as different from the intoxication caused by alcohol and other drugs. Dr. Andrew Wilson argues that for a significant minority, "amphetamines symbolised

7680-522: The amount of amphetamine used is the primary factor in determining the likelihood and severity of adverse effects. Amphetamine products such as Adderall , Dexedrine, and their generic equivalents are currently approved by the U.S. FDA for long-term therapeutic use. Recreational use of amphetamine generally involves much larger doses, which have a greater risk of serious adverse drug effects than dosages used for therapeutic purposes. Cardiovascular side effects can include hypertension or hypotension from

7800-451: The amphetamine-induced internalization of EAAT3 , a glutamate reuptake transporter, in dopamine neurons. Amphetamine also induces the selective release of histamine from mast cells and efflux from histaminergic neurons through VMAT2 . Acute amphetamine administration can also increase adrenocorticotropic hormone and corticosteroid levels in blood plasma by stimulating the hypothalamic–pituitary–adrenal axis . In December 2017,

7920-409: The atom permutations that moved that hydrogen are no longer valid. Only one permutation remains, that corresponds to flipping the molecule over while keeping the chlorine fixed. The five remaining hydrogens then fall into three different equivalence classes: the one opposite to the chlorine is a class by itself (called the para position), the two closest to the chlorine form another class ( ortho ), and

8040-429: The backbone of a typical protein would give a sequence of –[N—Cα—carbonyl C] n – etc. (when reading in the N to C direction). The α-carbon is where the different substituents attach to each different amino acid. That is, the groups hanging off the chain at the α-carbon are what give amino acids their diversity. These groups give the α-carbon its stereogenic properties for every amino acid except for glycine . Therefore,

8160-429: The bonds of the molecule. Likewise, all six hydrogens of ethane ( C 2 H 6 ) are structurally equivalent to each other, as are the two carbons; because any hydrogen can be switched with any other, either by a permutation that swaps just those two atoms, or by a permutation that swaps the two carbons and each hydrogen in one methyl group with a different hydrogen on the other methyl. Either operation preserves

8280-469: The brain, such as the right caudate nucleus of the basal ganglia . Reviews of clinical stimulant research have established the safety and effectiveness of long-term continuous amphetamine use for the treatment of ADHD. Randomized controlled trials of continuous stimulant therapy for the treatment of ADHD spanning 2 years have demonstrated treatment effectiveness and safety. Two reviews have indicated that long-term continuous stimulant therapy for ADHD

8400-500: The brain. The concentrations of the main neurotransmitters involved in reward circuitry and executive functioning, dopamine and norepinephrine, increase dramatically in a dose-dependent manner by amphetamine because of its effects on monoamine transporters . The reinforcing and motivational salience -promoting effects of amphetamine are due mostly to enhanced dopaminergic activity in the mesolimbic pathway . The euphoric and locomotor-stimulating effects of amphetamine are dependent upon

8520-402: The carbon atoms based on their substituents in order of precedence . For example, there are at least two isomers of the linear form of pentanone , a ketone that contains a chain of exactly five carbon atoms. There is an oxygen atom bonded to one of the middle three carbons (if it were bonded to an end carbon, the molecule would be an aldehyde , not a ketone), but it is not clear where it

8640-441: The clinical use of carbonic anhydrase inhibitors , carbonic anhydrase activation in other tissues may be associated with adverse effects, such as ocular activation exacerbating glaucoma . Alpha and beta carbon The International Union of Pure and Applied Chemistry (IUPAC) recommends the use of numeric prefixes to indicate the position of substituents, generally by identifying the parent hydrocarbon chain and assigning

8760-484: The cognitive processes responsible for overriding prepotent feeding responses that precede binge eating episodes. In addition, dextroamphetamine's actions outside of the central nervous system may also contribute to its treatment effects in BED. Peripherally, dextroamphetamine triggers lipolysis through noradrenergic signaling in adipose fat cells, leading to the release of triglycerides into blood plasma to be utilized as

8880-780: The cytosolic dopamine molecules are released from the presynaptic neuron into the synaptic cleft via reverse transport at DAT . Similar to dopamine, amphetamine dose-dependently increases the level of synaptic norepinephrine, the direct precursor of epinephrine . Based upon neuronal TAAR1 mRNA expression, amphetamine is thought to affect norepinephrine analogously to dopamine. In other words, amphetamine induces TAAR1-mediated efflux and non-competitive reuptake inhibition at phosphorylated NET , competitive NET reuptake inhibition, and norepinephrine release from VMAT2 . Amphetamine exerts analogous, yet less pronounced, effects on serotonin as on dopamine and norepinephrine. Amphetamine affects serotonin via VMAT2 and, like norepinephrine,

9000-451: 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. 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. These sexual addictions are associated with

9120-591: The fetus or newborns (i.e., it is not a human teratogen ), but amphetamine abuse does pose risks to the fetus. Amphetamine has also been shown to pass into breast milk, so the IPCS and the FDA advise mothers to avoid breastfeeding when using it. Due to the potential for reversible growth impairments, the FDA advises monitoring the height and weight of children and adolescents prescribed an amphetamine pharmaceutical. The adverse side effects of amphetamine are many and varied, and

9240-413: The first carbon atom that attaches to a functional group , such as a carbonyl . The second carbon atom is called the β-carbon ( beta -carbon), the third is the γ-carbon ( gamma -carbon), and the naming system continues in alphabetical order. The nomenclature can also be applied to the hydrogen atoms attached to the carbon atoms. A hydrogen atom attached to an α-carbon is called an α-hydrogen ,

9360-459: The first interpretation; but replacing two of the hydrogen atoms ( H) by deuterium atoms ( H) may yield any of two structural isotopomers (1,1-dideuteroethene and 1,2-dideuteroethene), if both carbon atoms are the same isotope. If, in addition, the two carbons are different isotopes (say, C and C), there would be three distinct structural isotopomers, since 1- C-1,1-dideuteroethene would be different from 1- C-2,2-dideuteroethene. And, in both cases,

9480-461: The first study assessing the interaction between amphetamine and human carbonic anhydrase enzymes was published; of the eleven carbonic anhydrase enzymes it examined, it found that amphetamine potently activates seven, four of which are highly expressed in the human brain , with low nanomolar through low micromolar activating effects. Based upon preclinical research, cerebral carbonic anhydrase activation has cognition-enhancing effects; but, based upon

9600-424: The highest efficacy (i.e., abstinence rate) and acceptability (i.e., lowest dropout rate). Other treatment modalities examined in the analysis included monotherapy with contingency management or community reinforcement approach, cognitive behavioral therapy , 12-step programs , non-contingent reward-based therapies, psychodynamic therapy , and other combination therapies involving these. Additionally, research on

9720-601: The human body. Phenethylamine is the parent compound of amphetamine, while N -methylphenethylamine is a positional isomer of amphetamine that differs only in the placement of the methyl group . Amphetamine is used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy (a sleep disorder), obesity , and, in the form of lisdexamfetamine , binge eating disorder . It is sometimes prescribed off-label for its past medical indications , particularly for depression and chronic pain . Long-term amphetamine exposure at sufficiently high doses in some animal species

9840-429: The human brain. Dextroamphetamine is a more potent agonist of TAAR1 than levoamphetamine. Consequently, dextroamphetamine produces greater CNS stimulation than levoamphetamine, roughly three to four times more, but levoamphetamine has slightly stronger cardiovascular and peripheral effects. In certain brain regions, amphetamine increases the concentration of dopamine in the synaptic cleft . Amphetamine can enter

9960-605: The hydroxyl group, which are fairly different from that of methyl ethyl ether. In chemistry, one usually ignores distinctions between isotopes of the same element. However, in some situations (for instance in Raman , NMR , or microwave spectroscopy ) one may treat different isotopes of the same element as different elements. In the second case, two molecules with the same number of atoms of each isotope but distinct bonding schemes are said to be structural isotopomers . Thus, for example, ethene would have no structural isomers under

10080-454: The induction of ΔFosB-mediated neural and behavioral plasticity by chronic drug use, which occurs via H3K9me2 -mediated repression of transcription factors for ΔFosB and H3K9me2-mediated repression of various ΔFosB transcriptional targets (e.g., CDK5 ). ΔFosB also plays an important role in regulating behavioral responses to natural rewards , such as palatable food, sex, and exercise. Since both natural rewards and addictive drugs induce

10200-427: The interacting substance, or both. Inhibitors of enzymes that metabolize amphetamine (e.g., CYP2D6 and FMO3 ) will prolong its elimination half-life , meaning that its effects will last longer. Amphetamine also interacts with MAOIs , particularly monoamine oxidase A inhibitors, since both MAOIs and amphetamine increase plasma catecholamines (i.e., norepinephrine and dopamine); therefore, concurrent use of both

10320-407: The latter. However, nitrostyrene's α-carbon atom is adjacent to the phenyl group; in phenethylamine this same carbon atom is the β-carbon atom, as phenethylamine (being an amine rather than a styrene) counts its atoms from the opposite "end" of the molecule. In proteins and amino acids , the α-carbon is the backbone carbon before the carbonyl carbon atom in the molecule. Therefore, reading along

10440-663: The magnitude and speed by which it increases synaptic dopamine and norepinephrine concentrations in the striatum . Amphetamine has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G s -coupled and G q -coupled G protein-coupled receptor (GPCR) discovered in 2001, which is important for regulation of brain monoamines. Activation of TAAR1 increases cAMP Tooltip cyclic adenosine monophosphate production via adenylyl cyclase activation and inhibits monoamine transporter function. Monoamine autoreceptors (e.g., D 2 short , presynaptic α 2 , and presynaptic 5-HT 1A ) have

10560-465: The methyl groups, and the two on the central carbon); therefore there are only two positional isomers of propanol ( 1-propanol and 2-propanol ). Likewise there are only two positional isomers of butanol , and three of pentanol or hexanol . Once a substitution is made on a parent molecule, its structural symmetry is usually reduced, meaning that atoms that were formerly equivalent may no longer be so. Thus substitution of two or more equivalent atoms by

10680-507: The molecule is named either pentan-2-one or pentan-3-one , depending on the position of the oxygen atom. Any side chains can be present in the place of oxygen and it can be defined as simply the number on the carbon to which any thing other than a hydrogen is attached. Another common system uses Greek letter prefixes as locants, which is useful in identifying the relative location of carbon atoms as well as hydrogen atoms to other functional groups. The α-carbon ( alpha -carbon) refers to

10800-425: The neuronal monoamine transporters , amphetamine also inhibits both vesicular monoamine transporters , VMAT1 and VMAT2 , as well as SLC1A1 , SLC22A3 , and SLC22A5 . SLC1A1 is excitatory amino acid transporter 3 (EAAT3), a glutamate transporter located in neurons, SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes , and SLC22A5 is a high-affinity carnitine transporter. Amphetamine

10920-438: The nucleus accumbens; magnesium ions inhibit NMDA receptors by blocking the receptor calcium channel . One review suggested that, based upon animal testing, pathological (addiction-inducing) psychostimulant use significantly reduces the level of intracellular magnesium throughout the brain. Supplemental magnesium treatment has been shown to reduce amphetamine self-administration (i.e., doses given to oneself) in humans, but it

11040-790: The number of binge eating days for the duration of the study. In addition, both a review and a meta-analytic systematic review found lisdexamfetamine to be superior to placebo in several secondary outcome measures, including persistent binge eating cessation, reduction of obsessive-compulsive related binge eating symptoms, reduction of body-weight, and reduction of triglycerides. Lisdexamfetamine, like all pharmaceutical amphetamines, has direct appetite suppressant effects that may be therapeutically useful in both BED and its comorbidities. Based on reviews of neuroimaging studies involving BED-diagnosed participants, therapeautic neuroplasticity in dopaminergic and noradrenergic pathways from long-term use of lisdexamfetamine may be implicated in lasting improvements in

11160-505: The occurrence of hyperpyrexia (i.e., core body temperature  ≥ 40 °C) is necessary for the development of amphetamine-induced neurotoxicity. 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. An amphetamine overdose can result in

11280-425: The only USFDA - and TGA -approved pharmacotherapy for BED. Evidence suggests that lisdexamfetamine's treatment efficacy in BED is underpinned at least in part by a psychopathological overlap between BED and ADHD, with the latter conceptualized as a cognitive control disorder that also benefits from treatment with lisdexamfetamine. Lisdexamfetamine's therapeutic effects for BED primarily involve direct action in

11400-743: The only post-synaptic receptor at which amphetamine is known to bind is the 5-HT1A receptor , where it acts as an agonist with low micromolar affinity. The full profile of amphetamine's short-term drug effects in humans is mostly derived through increased cellular communication or neurotransmission of dopamine , serotonin , norepinephrine , epinephrine , histamine , CART peptides , endogenous opioids , adrenocorticotropic hormone , corticosteroids , and glutamate , which it affects through interactions with CART , 5-HT1A , EAAT3 , TAAR1 , VMAT1 , VMAT2 , and possibly other biological targets . Amphetamine also activates seven human carbonic anhydrase enzymes, several of which are expressed in

11520-413: The onset of fatigue ), while improving reaction time . Amphetamine improves endurance and reaction time primarily through reuptake inhibition and release of dopamine in the central nervous system. 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

11640-442: The opposite effect of TAAR1, and together these receptors provide a regulatory system for monoamines. Notably, amphetamine and trace amines possess high binding affinities for TAAR1, but not for monoamine autoreceptors. Imaging studies indicate that monoamine reuptake inhibition by amphetamine and trace amines is site specific and depends upon the presence of TAAR1 co-localization in the associated monoamine neurons. In addition to

11760-433: The opposite. Due to the effect pH has on absorption, amphetamine also interacts with gastric acid reducers such as proton pump inhibitors and H 2 antihistamines , which increase gastrointestinal pH (i.e., make it less acidic). Amphetamine exerts its behavioral effects by altering the use of monoamines as neuronal signals in the brain, primarily in catecholamine neurons in the reward and executive function pathways of

11880-666: The other medications used in RCTs, which included antidepressants (bupropion, mirtazapine , sertraline ), antipsychotics ( aripiprazole ), anticonvulsants ( topiramate , baclofen , gabapentin ), naltrexone , varenicline , citicoline , ondansetron , prometa , riluzole , atomoxetine , dextroamphetamine, and modafinil . A 2018 systematic review and network meta-analysis of 50 trials involving 12 different psychosocial interventions for amphetamine, methamphetamine, or cocaine addiction found that combination therapy with both contingency management and community reinforcement approach had

12000-428: The oxygen atom is bonded. If the oxygen is bonded to the middle carbon, the locant is 3. If the oxygen is bonded to an atom on either side (adjacent to an end carbon), the locant is 2 or 4; given the choice here, where the carbons are exactly equivalent, the lower number is always chosen. So the locant is either 2 or 3 in this molecule. The locant is incorporated into the name of the molecule to remove ambiguity. Thus

12120-671: The quality of evidence for these findings is low and is consequently reflected in the AASM's conditional recommendation for dextroamphetamine as a treatment option for narcolepsy. In 2015, a systematic review and a meta-analysis of high quality clinical trials found that, when used at low (therapeutic) doses, amphetamine produces modest yet unambiguous improvements in cognition, including working memory , long-term episodic memory , inhibitory control , and some aspects of attention , in normal healthy adults; these cognition-enhancing effects of amphetamine are known to be partially mediated through

12240-438: The regulation of eating behaviors that are observed even after the drug is discontinued. Narcolepsy is a chronic sleep-wake disorder that is associated with excessive daytime sleepiness, cataplexy , and sleep paralysis . Patients with narcolepsy are diagnosed as either type 1 or type 2, with only the former presenting cataplexy symptoms. Type 1 narcolepsy results from the loss of approximately 70,000 orexin -releasing neurons in

12360-403: The remaining two are the third class ( meta ). Thus a second substitution of hydrogen by chlorine can yield three positional isomers: 1,2- or ortho - , 1,3- or meta - , and 1,4- or para -dichlorobenzene . For the same reason, there is only one phenol (hydroxybenzene), but three benzenediols ; and one toluene (methylbenzene), but three toluols , and three xylenes . On the other hand,

12480-411: The risk of developing a substance use disorder as an adult. Current models of ADHD suggest that it is associated with functional impairments in some of the brain's neurotransmitter systems ; these functional impairments involve impaired dopamine neurotransmission in the mesocorticolimbic projection and norepinephrine neurotransmission in the noradrenergic projections from the locus coeruleus to

12600-604: The same molecular formula C 4 H 10 O but are three distinct structural isomers. The concept applies also to polyatomic ions with the same total charge. A classical example is the cyanate ion O=C=N and the fulminate ion C ≡N −O . It is also extended to ionic compounds, so that (for example) ammonium cyanate [NH 4 ] [O=C=N] and urea (H 2 N−) 2 C=O are considered structural isomers, and so are methylammonium formate [H 3 C−NH 3 ] [HCO 2 ] and ammonium acetate [NH 4 ] [H 3 C−CO 2 ] . Structural isomerism

12720-469: The same element may generate more than one positional isomer. The classical example is the derivatives of benzene . Its six hydrogens are all structurally equivalent, and so are the six carbons; because the structure is not changed if the atoms are permuted in ways that correspond to flipping the molecule over or rotating it by multiples of 60 degrees. Therefore, replacing any hydrogen by chlorine yields only one chlorobenzene . However, with that replacement,

12840-437: The same significant functional group (the hydroxyl –OH) and are both alcohols. Besides the different chemistry, functional isomers typically have very different infrared spectra . The infrared spectrum is largely determined by the vibration modes of the molecule, and functional groups like hydroxyl and esters have very different vibration modes. Thus 1-propanol and 2-propanol have relatively similar infrared spectra because of

12960-829: The same structure, so there are only three structurally distinct trichlorobenzenes : 1,2,3- , 1,2,4- , and 1,3,5- . If the substituents at each step are different, there will usually be more structural isomers. Xylenol , which is benzene with one hydroxyl substituent and two methyl substituents, has a total of 6 isomers: Enumerating or counting structural isomers in general is a difficult problem, since one must take into account several bond types (including delocalized ones), cyclic structures, and structures that cannot possibly be realized due to valence or geometric constraints, and non-separable tautomers. For example, there are nine structural isomers with molecular formula C 3 H 6 O having different bond connectivities. Seven of them are air-stable at room temperature, and these are given in

13080-443: The second replacement (by the same substituent) may preserve or even increase the symmetry of the molecule, and thus may preserve or reduce the number of equivalence classes for the next replacement. Thus, the four remaining hydrogens in meta -dichlorobenzene still fall into three classes, while those of ortho - fall into two, and those of para - are all equivalent again. Still, some of these 3 + 2 + 1 = 6 substitutions end up yielding

13200-561: The severity of withdrawal symptoms is positively correlated with the age of the individual and the extent of their dependence. Mild withdrawal symptoms from the discontinuation of amphetamine treatment at therapeutic doses can be avoided by tapering the dose. An amphetamine overdose can lead to many different symptoms, but is rarely fatal with appropriate care. The severity of overdose symptoms increases with dosage and decreases with drug tolerance to amphetamine. Tolerant individuals have been known to take as much as 5 grams of amphetamine in

13320-416: The skeleton is acyclic , as in the above example, one may use the term chain isomerism . Position isomers (also positional isomers or regioisomers ) are structural isomers that can be viewed as differing only on the position of a functional group , substituent , or some other feature on the same "parent" structure. For example, replacing one of the 12 hydrogen atoms –H by a hydroxyl group –OH on

13440-424: The smart, on-the-ball, cool image" and that they sought "stimulation not intoxication [...] greater awareness, not escape" and " confidence and articulacy" rather than the " drunken rowdiness of previous generations." 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

13560-443: The structure of the molecule. That is the case also for the hydrogen atoms cyclopentane , allene , 2-butyne , hexamethylenetetramine , prismane , cubane , dodecahedrane , etc. On the other hand, the hydrogen atoms of propane are not all structurally equivalent. The six hydrogens attached to the first and third carbons are equivalent, as in ethane, and the two attached to the middle carbon are equivalent to each other; but there

13680-410: The teeth , nosebleed, profuse sweating, rhinitis medicamentosa (drug-induced nasal congestion), reduced seizure threshold , tics (a type of movement disorder), and weight loss . Dangerous physical side effects are rare at typical pharmaceutical doses. Amphetamine stimulates the medullary respiratory centers , producing faster and deeper breaths. In a normal person at therapeutic doses, this effect

13800-597: The therapeutic range can interfere with working memory and other aspects of cognitive control. Amphetamine is used by some athletes for its psychological and athletic performance-enhancing effects , such as increased endurance and alertness; however, non-medical amphetamine use is prohibited at sporting events that are regulated by collegiate, national, and international anti-doping agencies. In healthy people at oral therapeutic doses, amphetamine has been shown to increase muscle strength , acceleration, athletic performance in anaerobic conditions , and endurance (i.e., it delays

13920-643: The treatment of both type 1 and type 2 narcolepsy. Treatment with pharmaceutical amphetamines is generally less preferred relative to other stimulants (e.g., modafinil ) and is considered a third-line treatment option. Medical reviews indicate that amphetamine is safe and effective for the treatment of narcolepsy. Amphetamine appears to be most effective at improving symptoms associated with hypersomnolence , with three reviews finding clinically significant reductions in daytime sleepiness in patients with narcolepsy. Additionally, these reviews suggest that amphetamine may dose-dependently improve cataplexy symptoms. However,

14040-588: 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 . 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.   Binge eating disorder (BED)

14160-491: The user's personality and current mental state. Amphetamine psychosis (e.g., delusions and paranoia ) can occur in heavy users. Although very rare, this psychosis can also occur at therapeutic doses during long-term therapy. According to the FDA, "there is no systematic evidence" that stimulants produce aggressive behavior or hostility. Amphetamine has also been shown to produce a conditioned place preference in humans taking therapeutic doses, meaning that individuals acquire

14280-409: The α-carbon is a stereocenter for every amino acid except glycine. Glycine also does not have a β-carbon, while every other amino acid does. The α-carbon of an amino acid is significant in protein folding . When describing a protein, which is a chain of amino acids, one often approximates the location of each amino acid as the location of its α-carbon. In general, α-carbons of adjacent amino acids in

14400-833: Was used to treat a variety of conditions. Currently, pharmaceutical amphetamine is prescribed as racemic amphetamine, Adderall , dextroamphetamine , or the inactive prodrug lisdexamfetamine . Amphetamine increases monoamine and excitatory neurotransmission in the brain, with its most pronounced effects targeting the norepinephrine and dopamine neurotransmitter systems . At therapeutic doses, amphetamine causes emotional and cognitive effects such as euphoria , change in desire for sex , increased wakefulness , and improved cognitive control . It induces physical effects such as improved reaction time, fatigue resistance, decreased appetite , elevated heart rate, and increased muscle strength. Larger doses of amphetamine may impair cognitive function and induce rapid muscle breakdown . Addiction

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