Editing Stimulant (section)

=== Amphetamines (class) ===
{{Main|Substituted amphetamines}}

[[Substituted amphetamines]] are a [[chemical class|class of compounds]] based upon the [[amphetamine]] structure;<ref name="Amphetamine - a substituted amphetamine" /> it includes all [[derivative (chemistry)|derivative]] compounds which are formed by replacing, or [[substitution reaction|substituting]], one or more [[hydrogen atom]]s in the amphetamine core structure with [[substituent]]s.<ref name="Amphetamine - a substituted amphetamine">{{cite journal | vauthors = Hagel JM, Krizevski R, Marsolais F, Lewinsohn E, Facchini PJ | title = Biosynthesis of amphetamine analogs in plants | journal = Trends Plant Sci. | volume = 17 | issue = 7 | pages = 404–412 | date = 2012 | pmid = 22502775 | doi = 10.1016/j.tplants.2012.03.004 | bibcode = 2012TPS....17..404H | quote = 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). Countless variation in functional group substitutions has yielded a collection of synthetic drugs with diverse pharmacological properties as stimulants, empathogens and hallucinogens [3].&nbsp;... Beyond (1''R'',2''S'')-ephedrine and (1''S'',2''S'')-pseudoephedrine, myriad other substituted amphetamines have important pharmaceutical applications. The stereochemistry at the α-carbon is often a key determinant of pharmacological activity, with (''S'')-enantiomers being more potent. For example, (''S'')-amphetamine, commonly known as d-amphetamine or dextroamphetamine, displays five times greater psychostimulant activity compared with its (''R'')-isomer [78]. Most such molecules are produced exclusively through chemical syntheses and many are prescribed widely in modern medicine. For example, (''S'')-amphetamine (Figure 4b), a key ingredient in Adderall and Dexedrine, is used to treat attention deficit hyperactivity disorder (ADHD) [79].&nbsp;... <br />[Figure 4](b) Examples of synthetic, pharmaceutically important substituted amphetamines.}}</ref><ref name="Substituted amphetamines">{{cite book | author=Glennon RA | veditors=Lemke TL, Williams DA, Roche VF, Zito W | title=Foye's principles of medicinal chemistry | date=2013 | publisher=Wolters Kluwer Health/Lippincott Williams & Wilkins | location=Philadelphia, USA | isbn=978-1-60913-345-0 | pages=646–648 | edition=7th | section-url=https://books.google.com/books?id=Sd6ot9ul-bUC&q=substituted%20derivatives%20substituents%20amphetamine%20substitution&pg=PA646 | section=Phenylisopropylamine stimulants: amphetamine-related agents | quote=The simplest unsubstituted phenylisopropylamine, 1-phenyl-2-aminopropane, or amphetamine, serves as a common structural template for hallucinogens and psychostimulants. Amphetamine produces central stimulant, anorectic, and sympathomimetic actions, and it is the prototype member of this class (39). | access-date=25 October 2020 | archive-date=25 March 2024 | archive-url=https://web.archive.org/web/20240325205904/https://books.google.com/books?id=Sd6ot9ul-bUC&q=substituted%20derivatives%20substituents%20amphetamine%20substitution&pg=PA646#v=snippet&q=substituted%20derivatives%20substituents%20amphetamine%20substitution&f=false | url-status=live }}</ref><ref name="pmid1855720">{{cite journal | vauthors = Lillsunde P, Korte T | title = Determination of ring- and N-substituted amphetamines as heptafluorobutyryl derivatives | journal = Forensic Sci. Int. | volume = 49 | issue = 2 | pages = 205–213 | date = March 1991 | pmid = 1855720 | doi=10.1016/0379-0738(91)90081-s}}</ref> Examples of substituted amphetamines are amphetamine (itself),<ref name="Amphetamine - a substituted amphetamine" /><ref name="Substituted amphetamines" /> [[methamphetamine]],<ref name="Amphetamine - a substituted amphetamine" /> [[ephedrine]],<ref name="Amphetamine - a substituted amphetamine" /> [[cathinone]],<ref name="Amphetamine - a substituted amphetamine" /> [[phentermine]],<ref name="Amphetamine - a substituted amphetamine" /> [[mephentermine]],<ref name="Amphetamine - a substituted amphetamine" /> [[bupropion]],<ref name="Amphetamine - a substituted amphetamine" /> [[methoxyphenamine]],<ref name="Amphetamine - a substituted amphetamine" /> [[selegiline]],<ref name="Amphetamine - a substituted amphetamine" /> [[amfepramone]],<ref name="Amphetamine - a substituted amphetamine" /> [[pyrovalerone]],<ref name="Amphetamine - a substituted amphetamine" /> [[MDMA]] (ecstasy), and [[2,5-dimethoxy-4-methylamphetamine|DOM]] (STP). Many drugs in this class work primarily by activating [[trace amine-associated receptor 1]] (TAAR1);<ref name="Miller" /> in turn, this causes [[reuptake inhibition]] and effluxion, or release, of [[dopamine]], [[norepinephrine]], and [[serotonin]].<ref name="Miller" /> An additional mechanism of some substituted amphetamines is the release of [[synaptic vesicle|vesicular stores]] of [[monoamine neurotransmitter]]s through [[VMAT2]], thereby increasing the concentration of these neurotransmitters in the [[cytosol]], or intracellular fluid, of the [[presynaptic neuron]].<ref name="E Weihe">{{cite journal |vauthors=Eiden LE, Weihe E | title = VMAT2: a dynamic regulator of brain monoaminergic neuronal function interacting with drugs of abuse | journal = Ann. N. Y. Acad. Sci. | volume = 1216 | issue = 1| pages = 86–98 |date=January 2011 | pmid = 21272013 | doi = 10.1111/j.1749-6632.2010.05906.x | pmc=4183197| bibcode = 2011NYASA1216...86E }}</ref>

Amphetamine-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat [[major depressive disorder]], where subjects do not respond well to traditional [[selective serotonin reuptake inhibitor]] (SSRI) medications,{{Citation needed|date=May 2015}} but evidence supporting this use is mixed.<ref name="pmid17338594"/> Two large [[Phase III clinical trials|phase III]] studies of [[lisdexamfetamine]] (a [[prodrug]] to amphetamine) as an adjunct to an SSRI or [[serotonin–norepinephrine reuptake inhibitor]] (SNRI) in the treatment of major depressive disorder showed no further benefit relative to placebo in effectiveness.<ref name="DaleBang-Andersen2015">{{cite journal|last1=Dale|first1=Elena|last2=Bang-Andersen|first2=Benny|last3=Sánchez|first3=Connie|title=Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs|journal=Biochemical Pharmacology|volume=95|issue=2|year=2015|pages=81–97|issn=0006-2952|doi=10.1016/j.bcp.2015.03.011|pmid=25813654|doi-access=free}}</ref> Numerous studies have demonstrated the effectiveness of drugs like [[Adderall]] (a mixture of [[salt (chemistry)|salts]] of amphetamine and [[dextroamphetamine]]) in controlling symptoms associated with [[ADHD]]. Non-stimulants such as [[atomoxetine]] have also found to be effective.<ref>{{Cite report |url=https://effectivehealthcare.ahrq.gov/products/attention-deficit-hyperactivity-disorder/research |title=ADHD Diagnosis and Treatment in Children and Adolescents |last1=Peterson |first1=Bradley S. |last2=Trampush |first2=Joey |last3=Maglione |first3=Margaret |last4=Bolshakova |first4=Maria |last5=Brown |first5=Morah |last6=Rozelle |first6=Mary |last7=Motala |first7=Aneesa |last8=Yagyu |first8=Sachi |last9=Miles |first9=Jeremy |date=2024-03-25 |publisher=Agency for Healthcare Research and Quality (AHRQ) |doi=10.23970/ahrqepccer267}}</ref> Due to their availability and fast-acting effects, substituted amphetamines are prime candidates for abuse.<ref name="www.drugabuse.gov">[http://www.drugabuse.gov/Testimony/7-26-06Testimony.html Efforts of the National Institute on Drug Abuse to Prevent and Treat Prescription Drug Abuse] {{webarchive|url=https://web.archive.org/web/20070929083259/http://www.drugabuse.gov/Testimony/7-26-06Testimony.html |date=29 September 2007 }}, Testimony Before the Subcommittee on Criminal Justice, Drug Policy, and Human Resources Committee on Government Reform, United States House of Representatives, 26 July 2006</ref>