Amphetamine enters the presynaptic neuron across the neuronal membrane or through DAT. Once inside, it binds to TAAR1 or enters synaptic vesicles through VMAT2. When amphetamine enters the synaptic vesicles through VMAT2, dopamine is released into the cytosol (yellow-orange area). When amphetamine binds to TAAR1, it reduces postsynaptic neuron firing rate via potassium channels（英语：G protein-coupled inwardly-rectifying potassium channel） and triggers protein kinase A (PKA) and protein kinase C (PKC) signaling, resulting in DAT phosphorylation. PKA-phosphorylation causes DAT to withdraw into the presynaptic neuron (internalize) and cease transport. PKC-phosphorylated DAT may either operate in reverse or, like PKA-phosphorylated DAT, internalize and cease transport. Amphetamine is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a CAMKIIα（英语：CAMKIIα）-dependent pathway, in turn producing dopamine efflux.
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.
有一個「安非他命」類的定義嚴格限定分類中僅有：安非他命的racemate and enantiomers和甲基安非他命methamphetamine的racemate and enantiomers。
為避免讀者混淆，本條目中僅會使用amphetamine、amphetamines來表示racemic amphetamine, levoamphetamine, and dextroamphetamine；安非他命衍生物（substituted amphetamines）來表示安非他命的結構分類。
^For uniformity, molecular masses were calculated using the Lenntech Molecular Weight Calculator and were within 0.01g/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.
^This product (Dyanavel XR) is an oral suspension (i.e., a drug that is suspended in a liquid and taken by mouth) that contains 2.5 mg/mL of amphetamine base. The product uses an ion exchange resin to achieve extended release of the amphetamine base.
^ 1.01.11.21.188.8.131.52.71.81.9Heal DJ, Smith SL, Gosden J, Nutt DJ. Amphetamine, past and present – a pharmacological and clinical perspective. J. Psychopharmacol. June 2013, 27 (6): 479–496. PMC 3666194. PMID 23539642. doi:10.1177/0269881113482532. The intravenous use of d-amphetamine and other stimulants still pose major safety risks to the individuals indulging in this practice. Some of this intravenous abuse is derived from the diversion of ampoules of d-amphetamine, which are still occasionally prescribed in the UK for the control of severe narcolepsy and other disorders of excessive sedation. ... For these reasons, observations of dependence and abuse of prescription d-amphetamine are rare in clinical practice, and this stimulant can even be prescribed to people with a history of drug abuse provided certain controls, such as daily pick-ups of prescriptions, are put in place (Jasinski and Krishnan, 2009b).
^ 2.02.1Pharmacology. Dextroamphetamine. DrugBank. University of Alberta. 2013-02-08 [2013-11-05]. （原始内容存档于2019-08-06）.
^ 5.05.15.25.3Glennon RA. Phenylisopropylamine stimulants: amphetamine-related agents. Lemke TL, Williams DA, Roche VF, Zito W (编). Foye's principles of medicinal chemistry 7th. Philadelphia, USA: Wolters Kluwer Health/Lippincott Williams & Wilkins. 2013: 646–648 [2015-09-11]. ISBN 9781609133450. （原始内容存档于2019-06-09）. 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.
Horwitz D, Alexander RW, Lovenberg W, Keiser HR. Human serum dopamine-β-hydroxylase. Relationship to hypertension and sympathetic activity. Circ. Res. May 1973, 32 (5): 594–599. PMID 4713201. doi:10.1161/01.RES.32.5.594. Subjects with exceptionally low levels of serum dopamine-β-hydroxylase activity showed normal cardiovascular function and normal β-hydroxylation of an administered synthetic substrate, hydroxyamphetamine.
Cashman JR, Xiong YN, Xu L, Janowsky A. N-oxygenation of amphetamine and methamphetamine by the human flavin-containing monooxygenase (form 3): role in bioactivation and detoxication. J. Pharmacol. Exp. Ther. March 1999, 288 (3): 1251–1260. PMID 10027866.
^ 16.016.1Biological Half-Life. AMPHETAMINE. United States National Library of Medicine – Toxnet. Hazardous Substances Data Bank. [2014-01-05]. （原始内容存档于2017-10-02）. Concentrations of (14)C-amphetamine declined less rapidly in the plasma of human subjects maintained on an alkaline diet (urinary pH > 7.5) than those on an acid diet (urinary pH < 6). Plasma half-lives of amphetamine ranged between 16-31 hr & 8-11 hr, respectively, & the excretion of (14)C in 24 hr urine was 45 & 70%.
^ 18.018.118.2Compound Summary. Amphetamine. PubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information. 11 April 2015 [17 April 2015]. （原始内容存档于2013-10-13）.引用错误：带有name属性“PubChem Header”的<ref>标签用不同内容定义了多次
^Density. Amphetamine. PubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information. 5 November 2016 [9 November 2016]. （原始内容存档于2021-01-29）.
^Chemical and Physical Properties. Amphetamine. PubChem Compound. United States National Library of Medicine – National Center for Biotechnology Information. [13 October 2013]. （原始内容存档于2013-10-13）.
^Enantiomer. IUPAC Goldbook. International Union of Pure and Applied Chemistry. [2014-03-14]. doi:10.1351/goldbook.E02069. （原始内容存档于2013-03-17）. One of a pair of molecular entities which are mirror images of each other and non-superposable.
^ 23.023.1Guidelines on the Use of International Nonproprietary Names (INNS) for Pharmaceutical Substances. World Health Organization. 1997 [1 December 2014]. （原始内容存档于2015-01-09）. In principle, INNs are selected only for the active part of the molecule which is usually the base, acid or alcohol. In some cases, however, the active molecules need to be expanded for various reasons, such as formulation purposes, bioavailability or absorption rate. In 1975 the experts designated for the selection of INN decided to adopt a new policy for naming such molecules. In future, names for different salts or esters of the same active substance should differ only with regard to the inactive moiety of the molecule. ... The latter are called modified INNs (INNMs).
Malenka RC, Nestler EJ, Hyman SE. Chapter 13: Higher Cognitive Function and Behavioral Control. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York, USA: McGraw-Hill Medical. 2009: 318, 321. 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.
Liddle DG, Connor DJ. Nutritional supplements and ergogenic AIDS. Prim. Care. June 2013, 40 (2): 487–505. PMID 23668655. doi:10.1016/j.pop.2013.02.009. 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
^Amphetamine. European Monitoring Centre for Drugs and Drug Addiction. [2013-10-19]. （原始内容存档于2020-02-27）.
^Hagel JM, Krizevski R, Marsolais F, Lewinsohn E, Facchini PJ. Biosynthesis of amphetamine analogs in plants. Trends Plant Sci. 2012, 17 (7): 404–412. PMID 22502775. doi:10.1016/j.tplants.2012.03.004. Substituted amphetamines, which are also called phenylpropylamino alkaloids, are a diverse group of nitrogen-containing compounds that feature a phenethylamine backbone with a methyl group at the α-position relative to the nitrogen (Figure 1). ... Beyond (1R,2S)-ephedrine and (1S,2S)-pseudoephedrine, myriad other substituted amphetamines have important pharmaceutical applications. ... For example, (S)-amphetamine (Figure 4b), a key ingredient in Adderall® and Dexedrine®, is used to treat attention deficit hyperactivity disorder (ADHD) . ... [Figure 4](b) Examples of synthetic, pharmaceutically important substituted amphetamines.
^ 39.039.1Hart H, Radua J, Nakao T, Mataix-Cols D, Rubia K. Meta-analysis of functional magnetic resonance imaging studies of inhibition and attention in attention-deficit/hyperactivity disorder: exploring task-specific, stimulant medication, and age effects. JAMA Psychiatry. February 2013, 70 (2): 185–198. PMID 23247506. doi:10.1001/jamapsychiatry.2013.277.
Frodl T, Skokauskas N. Meta-analysis of structural MRI studies in children and adults with attention deficit hyperactivity disorder indicates treatment effects.. Acta psychiatrica Scand. February 2012, 125 (2): 114–126. PMID 22118249. doi:10.1111/j.1600-0447.2011.01786.x. 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.
Millichap JG. Chapter 9: Medications for ADHD. Millichap JG (编). Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD 2nd. New York, USA: Springer. 2010: 121–123, 125–127. 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.
^ 45.045.145.245.345.4Huang YS, Tsai MH. Long-term outcomes with medications for attention-deficit hyperactivity disorder: current status of knowledge. CNS Drugs. July 2011, 25 (7): 539–554. PMID 21699268. doi:10.2165/11589380-000000000-00000. 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. ... 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.
Malenka RC, Nestler EJ, Hyman SE. Chapter 6: Widely Projecting Systems: Monoamines, Acetylcholine, and Orexin. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York, USA: McGraw-Hill Medical. 2009: 154–157. ISBN 9780071481274.
Millichap JG. Chapter 9: Medications for ADHD. Millichap JG (编). Attention Deficit Hyperactivity Disorder Handbook: A Physician's Guide to ADHD 2nd. New York, USA: Springer. 2010: 111–113. ISBN 9781441913968.
Punja S, Shamseer L, Hartling L, Urichuk L, Vandermeer B, Nikles J, Vohra S. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst. Rev. February 2016, 2: CD009996. PMID 26844979. doi:10.1002/14651858.CD009996.pub2.
^Pringsheim T, Steeves T. Pringsheim T , 编. Pharmacological treatment for Attention Deficit Hyperactivity Disorder (ADHD) in children with comorbid tic disorders. Cochrane Database Syst. Rev. April 2011, (4): CD007990. PMID 21491404. doi:10.1002/14651858.CD007990.pub2.
^Methylphenidate. Home of MedlinePlus → Drugs, Herbs and Supplements → Methylphenidate Methylphenidate pronounced as (meth il fen i date). 2016-02-15 [2017-02-27]. （原始内容存档于2017-07-04）.
^Combining medications could offer better results for ADHD patients. Science News. Elsevier. 2016-08-01 [January 2017]. （原始内容存档于2017-01-02）. "Three studies to be published in the August 2016 issue of the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP) report that combining two standard medications could lead to greater clinical improvements for children with attention-deficit/hyperactivity disorder (ADHD) than either ADHD therapy alone.", August, 2016
^Adults with ADHD. MedlinePlus the Magazine 9. 8600 Rockville Pike · Bethesda, MD 20894, United States of America: NATIONAL LIBRARY OF MEDICINE at the NATIONAL INSTITUTES OF HEALTH. Spring 2014: 19 [2017-04-05]. ISSN 1937-4712. （原始内容存档于2017-07-15） （美国英语）.
^Attention deficit hyperactivity disorder. Home → Medical Encyclopedia → Attention deficit hyperactivity disorder. NATIONAL LIBRARY OF MEDICINE at the NATIONAL INSTITUTES OF HEALTH. 2016-05-25 [2017-02-27]. （原始内容存档于2017-01-26）.
^All Disorders. National Institute of Neurological Disorders and Stroke. [2017-02-27]. （原始内容存档于2016-12-02）.
^ 64.064.1Spencer RC, Devilbiss DM, Berridge CW. The Cognition-Enhancing Effects of Psychostimulants Involve Direct Action in the Prefrontal Cortex. Biol. Psychiatry. June 2015, 77 (11): 940–950. PMID 25499957. doi:10.1016/j.biopsych.2014.09.013. 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.
^Ilieva IP, Hook CJ, Farah MJ. Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis. J. Cogn. Neurosci. January 2015: 1–21. PMID 25591060. doi:10.1162/jocn_a_00776. 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.
Devous MD, Trivedi MH, Rush AJ. Regional cerebral blood flow response to oral amphetamine challenge in healthy volunteers. J. Nucl. Med. April 2001, 42 (4): 535–542. PMID 11337538.
Malenka RC, Nestler EJ, Hyman SE. Chapter 10: Neural and Neuroendocrine Control of the Internal Milieu. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York, USA: McGraw-Hill Medical. 2009: 266. ISBN 9780071481274. Dopamine acts in the nucleus accumbens to attach motivational significance to stimuli associated with reward.
Parr JW. Attention-deficit hyperactivity disorder and the athlete: new advances and understanding. Clin. Sports Med. July 2011, 30 (3): 591–610. PMID 21658550. doi:10.1016/j.csm.2011.03.007. 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.
Roelands B, de Koning J, Foster C, Hettinga F, Meeusen R. Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing. Sports Med. May 2013, 43 (5): 301–311. PMID 23456493. doi:10.1007/s40279-013-0030-4. 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.
Parker KL, Lamichhane D, Caetano MS, Narayanan NS. Executive dysfunction in Parkinson's disease and timing deficits. Front. Integr. Neurosci. October 2013, 7: 75. PMC 3813949. PMID 24198770. doi:10.3389/fnint.2013.00075. 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.
Roelands B, De Pauw K, Meeusen R. Neurophysiological effects of exercise in the heat. Scand. J. Med. Sci. Sports. June 2015,. 25 Suppl 1: 65–78. PMID 25943657. doi:10.1111/sms.12350. 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.
Kessler S. Drug therapy in attention-deficit hyperactivity disorder. South. Med. J. January 1996, 89 (1): 33–38. PMID 8545689. doi:10.1097/00007611-199601000-00005. 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.
Feinberg SS. Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication. J. Clin. Psychiatry. November 2004, 65 (11): 1520–1524. PMID 15554766. doi:10.4088/jcp.v65n1113.
^ 87.087.187.287.387.487.587.6Dyanavel XR Prescribing Information(PDF). Tris Pharmaceuticals: 1–16. October 2015 [2015-11-23]. （原始内容(PDF)存档于2016-10-13）. DYANAVEL XR contains d-amphetamine and l-amphetamine in a ratio of 3.2 to 1 ... The most common (≥2% in the DYANAVEL XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 108 patients with ADHD (aged 6–12 years) were: epistaxis, allergic rhinitis and upper abdominal pain. ... DOSAGE FORMS AND STRENGTHS Extended-release oral suspension contains 2.5 mg amphetamine base per mL.
^O'Connor PG. Amphetamines. Merck Manual for Health Care Professionals. Merck. February 2012 [2012-05-08]. （原始内容存档于2012-05-06）.
^ 95.095.195.295.3Shoptaw SJ, Kao U, Ling W. Shoptaw SJ, Ali R , 编. Treatment for amphetamine psychosis. Cochrane Database Syst. Rev. January 2009, (1): CD003026. PMID 19160215. doi:10.1002/14651858.CD003026.pub3. 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.
^ 98.098.1Malenka RC, Nestler EJ, Hyman SE. Chapter 15: Reinforcement and Addictive Disorders. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York: McGraw-Hill Medical. 2009: 364–375. ISBN 9780071481274.
^ 99.099.1Spiller HA, Hays HL, Aleguas A. Overdose of drugs for attention-deficit hyperactivity disorder: clinical presentation, mechanisms of toxicity, and management. CNS Drugs. June 2013, 27 (7): 531–543. PMID 23757186. doi:10.1007/s40263-013-0084-8. 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.
^ 103.0103.1103.2103.3103.4Ruffle JK. Molecular neurobiology of addiction: what's all the (Δ)FosB about?. Am. J. Drug Alcohol Abuse. November 2014, 40 (6): 428–437. PMID 25083822. doi:10.3109/00952990.2014.933840. ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure.
^ 106.00106.01106.02106.03106.04106.05106.06106.07106.08106.09106.10106.11106.12106.13106.14106.15106.16106.17106.18106.19106.20106.21Olsen CM. Natural rewards, neuroplasticity, and non-drug addictions. Neuropharmacology. December 2011, 61 (7): 1109–1122. PMC 3139704. PMID 21459101. doi:10.1016/j.neuropharm.2011.03.010. 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).
^ 107.0107.1107.2107.3Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA. Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis. Neurosci. Biobehav. Rev. September 2013, 37 (8): 1622–1644. PMC 3788047. PMID 23806439. doi:10.1016/j.neubiorev.2013.06.011. 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.
^ 108.0108.1108.2Zhou Y, Zhao M, Zhou C, Li R. Sex differences in drug addiction and response to exercise intervention: From human to animal studies. Front. Neuroendocrinol. July 2015, 40: 24–41. PMID 26182835. doi:10.1016/j.yfrne.2015.07.001. 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.
^ 110.0110.1Malenka RC, Nestler EJ, Hyman SE. Chapter 15: Reinforcement and Addictive Disorders. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York, USA: McGraw-Hill Medical. 2009: 386. ISBN 9780071481274. Currently, cognitive–behavioral therapies are the most successful treatment available for preventing the relapse of psychostimulant use.
^Malenka RC, Nestler EJ, Hyman SE. Chapter 15: Reinforcement and Addictive Disorders. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York: McGraw-Hill Medical. 2009: 368. ISBN 9780071481274. 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.
^Kollins SH. A qualitative review of issues arising in the use of psycho-stimulant medications in patients with ADHD and co-morbid substance use disorders. Curr. Med. Res. Opin. May 2008, 24 (5): 1345–1357. PMID 18384709. doi:10.1185/030079908X280707. 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.
^Stolerman IP. Stolerman IP , 编. Encyclopedia of Psychopharmacology. Berlin, Germany; London, England: Springer. 2010: 78. ISBN 9783540686989.
^Perez-Mana C, Castells X, Torrens M, Capella D, Farre M. Pérez-Mañá C , 编. Efficacy of psychostimulant drugs for amphetamine abuse or dependence. Cochrane Database Syst. Rev. September 2013, 9: CD009695. PMID 23996457. doi:10.1002/14651858.CD009695.pub2.
^Malenka RC, Nestler EJ, Hyman SE. Chapter 4: Signal Transduction in the Brain. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York, USA: McGraw-Hill Medical. 2009: 94. ISBN 9780071481274.
^Perez-Mana C, Castells X, Torrens M, Capella D, Farre M. Efficacy of psychostimulant drugs for amphetamine abuse or dependence. Cochrane Database Syst. Rev. September 2013, 9: CD009695. PMID 23996457. doi:10.1002/14651858.CD009695.pub2. To date, no pharmacological treatment has been approved for [addiction], and psychotherapy remains the mainstay of treatment. ... Results of this review do not support the use of psychostimulant medications at the tested doses as a replacement therapy
^ 133.0133.1133.2133.3Grandy DK, Miller GM, Li JX. "TAARgeting Addiction"-The Alamo Bears Witness to Another Revolution: An Overview of the Plenary Symposium of the 2015 Behavior, Biology and Chemistry Conference. Drug Alcohol Depend. February 2016, 159: 9–16. PMID 26644139. doi:10.1016/j.drugalcdep.2015.11.014. 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.
^ 135.0135.1Malenka RC, Nestler EJ, Hyman SE. Chapter 5: Excitatory and Inhibitory Amino Acids. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York, USA: McGraw-Hill Medical. 2009: 124–125. ISBN 9780071481274.
^ 136.0136.1136.2Carroll ME, Smethells JR. Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments. Front. Psychiatry. February 2016, 6: 175. PMC 4745113. PMID 26903885. doi:10.3389/fpsyt.2015.00175. 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.
^ 137.0137.1137.2137.3Shoptaw SJ, Kao U, Heinzerling K, Ling W. Shoptaw SJ , 编. Treatment for amphetamine withdrawal. Cochrane Database Syst. Rev. April 2009, (2): CD003021. PMID 19370579. doi:10.1002/14651858.CD003021.pub2. 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) ...
^Amphetamine. Hazardous Substances Data Bank. United States National Library of Medicine – Toxicology Data Network. [2014-02-26]. （原始内容存档于2017-10-02）. Direct toxic damage to vessels seems unlikely because of the dilution that occurs before the drug reaches the cerebral circulation.
^Malenka RC, Nestler EJ, Hyman SE. Chapter 15: Reinforcement and addictive disorders. Sydor A, Brown RY (编). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience 2nd. New York, USA: McGraw-Hill Medical. 2009: 370. ISBN 9780071481274. Unlike cocaine and amphetamine, methamphetamine is directly toxic to midbrain dopamine neurons.
^ 150.0150.1Neal R. Swerdlow. Savita G. Bhakta , Jo Talledo, Lindsay Benster, Juliana Kotz, Maria Lavadia and Gregory A. Light. Lessons learned by giving amphetamine to antipsychotic-medicated schizophrenia patients. Neurophsychopharmacology. 2019.
^Hofmann FG. A Handbook on Drug and Alcohol Abuse: The Biomedical Aspects 2nd. New York, USA: Oxford University Press. 1983: 329. ISBN 9780195030570.
^Krause J. SPECT and PET of the dopamine transporter in attention-deficit/hyperactivity disorder. Expert Rev. Neurother. April 2008, 8 (4): 611–625. PMID 18416663. doi:10.1586/14737184.108.40.2061. Zinc binds at ... extracellular sites of the DAT , 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.
^ 155.0155.1Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH. The role of zinc ions in reverse transport mediated by monoamine transporters. J. Biol. Chem. June 2002, 277 (24): 21505–21513. PMID 11940571. doi:10.1074/jbc.M112265200. The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2+ binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). ... Although Zn2+ inhibited uptake, Zn2+ facilitated [3H]MPP+ release induced by amphetamine, MPP+, or K+-induced depolarization specifically at hDAT but not at the human serotonin and the norepinephrine transporter (hNET).
^Scassellati C, Bonvicini C, Faraone SV, Gennarelli M. Biomarkers and attention-deficit/hyperactivity disorder: a systematic review and meta-analyses. J. Am. Acad. Child Adolesc. Psychiatry. October 2012, 51 (10): 1003–1019.e20. PMID 23021477. doi:10.1016/j.jaac.2012.08.015. With regard to zinc supplementation, a placebo controlled trial reported that doses up to 30 mg/day of zinc were safe for at least 8 weeks, but the clinical effect was equivocal except for the finding of a 37% reduction in amphetamine optimal dose with 30 mg per day of zinc.110
^Richard RA. Route of Administration. Chapter 5—Medical Aspects of Stimulant Use Disorders. National Center for Biotechnology Information Bookshelf. Treatment Improvement Protocol 33. Substance Abuse and Mental Health Services Administration. 1999 [2017-04-06]. （原始内容存档于2020-11-11）.
^ 167.0167.1Underhill SM, Wheeler DS, Li M, Watts SD, Ingram SL, Amara SG. Amphetamine modulates excitatory neurotransmission through endocytosis of the glutamate transporter EAAT3 in dopamine neurons. Neuron. July 2014, 83 (2): 404–416. PMC 4159050. PMID 25033183. doi:10.1016/j.neuron.2014.05.043. 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
^Rytting E, Audus KL. Novel organic cation transporter 2-mediated carnitine uptake in placental choriocarcinoma (BeWo) cells. J. Pharmacol. Exp. Ther. January 2005, 312 (1): 192–198. PMID 15316089. doi:10.1124/jpet.104.072363.
^Inazu M, Takeda H, Matsumiya T. [The role of glial monoamine transporters in the central nervous system]. Nihon Shinkei Seishin Yakurigaku Zasshi. August 2003, 23 (4): 171–178. PMID 13677912（日语）.
^ 173.0173.1173.2Vicentic A, Jones DC. The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction. J. Pharmacol. Exp. Ther. February 2007, 320 (2): 499–506. PMID 16840648. doi:10.1124/jpet.105.091512. The physiological importance of CART was further substantiated in numerous human studies demonstrating a role of CART in both feeding and psychostimulant addiction. ... Colocalization studies also support a role for CART in the actions of psychostimulants. ... CART and DA receptor transcripts colocalize (Beaudry et al., 2004). Second, dopaminergic nerve terminals in the NAc synapse on CART-containing neurons (Koylu et al., 1999), hence providing the proximity required for neurotransmitter signaling. These studies suggest that DA plays a role in regulating CART gene expression possibly via the activation of CREB.
^Zhang M, Han L, Xu Y. Roles of cocaine- and amphetamine-regulated transcript in the central nervous system. Clin. Exp. Pharmacol. Physiol. June 2012, 39 (6): 586–592. PMID 22077697. doi:10.1111/j.1440-1681.2011.05642.x. Recently, it was demonstrated that CART, as a neurotrophic peptide, had a cerebroprotective against focal ischaemic stroke and inhibited the neurotoxicity of β-amyloid protein, which focused attention on the role of CART in the central nervous system (CNS) and neurological diseases. ... The literature indicates that there are many factors, such as regulation of the immunological system and protection against energy failure, that may be involved in the cerebroprotection afforded by CART
^Finnema SJ, Scheinin M, Shahid M, Lehto J, Borroni E, Bang-Andersen B, Sallinen J, Wong E, Farde L, Halldin C, Grimwood S. Application of cross-species PET imaging to assess neurotransmitter release in brain. Psychopharmacology. November 2015, 232 (21–22): 4129–4157. PMC 4600473. PMID 25921033. doi:10.1007/s00213-015-3938-6. More recently, Colasanti and colleagues reported that a pharmacologically induced elevation in endogenous opioid release reduced [11C]carfentanil binding in several regions of the human brain, including the basal ganglia, frontal cortex, and thalamus (Colasanti et al. 2012). Oral administration of d-amphetamine, 0.5 mg/kg, 3 h before [11C]carfentanil injection, reduced BPND values by 2–10 %. The results were confirmed in another group of subjects (Mick et al. 2014). However, Guterstam and colleagues observed no change in [11C]carfentanil binding when d-amphetamine, 0.3 mg/kg, was administered intravenously directly before injection of [11C]carfentanil (Guterstam et al. 2013). It has been hypothesized that this discrepancy may be related to delayed increases in extracellular opioid peptide concentrations following amphetamine-evoked monoamine release (Colasanti et al. 2012; Mick et al. 2014).
^Adzenys XR Prescribing Information(PDF). United States Food and Drug Administration. Neos Therapeutics, Inc.: 15. January 2016 [2016-03-07]. （原始内容存档(PDF)于2020-10-30）. ADZENYS XR-ODT (amphetamine extended-release orally disintegrating tablet) contains a 3 to 1 ratio of d- to l-amphetamine, a central nervous system stimulant.
^Adzenys XR. United States Food and Drug Administration. [2016-03-07].
^Dyanavel XR. United States Food and Drug Administration. [2016-01-01].
^Evekeo. United States Food and Drug Administration. [2015-08-11].