Editing Stimulant (section)

==Mechanisms of action==
Most stimulants exert their activating effects by enhancing [[catecholamine]] neurotransmission. Catecholamine neurotransmitters are employed in regulatory pathways implicated in attention, arousal, motivation, task salience and reward anticipation. Classical stimulants either [[Monoamine reuptake inhibitor|block the reuptake]] or [[Monoamine releasing agent|stimulate the efflux]] of these catecholamines, resulting in increased activity of their circuits. Some stimulants, specifically those with [[empathogen]]ic and [[hallucinogen]]ic effects, also affect [[Serotonin|serotonergic]] transmission. Some stimulants, such as some amphetamine derivatives{{which|date=May 2024}} and, notably, [[yohimbine]], can decrease [[negative feedback]] by antagonizing regulatory [[autoreceptor]]s.<ref name="pmid18500382">{{cite journal|last1=Docherty|first1=J R|title=Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)|journal=British Journal of Pharmacology|date=7 January 2017|volume=154|issue=3|pages=606–622|doi=10.1038/bjp.2008.124|pmc=2439527|issn=0007-1188|pmid=18500382}}</ref> [[Adrenergic agonist]]s, such as, in part, [[ephedrine]], act by directly binding to and activating [[adrenergic receptor]]s, producing sympathomimetic effects.{{citation needed |date=May 2024}} <!-- I honestly haven't found a good reference with respect to ephedrine or pseudoephedrine mechanism, and many direct agonists such as albuterol (salbutamol) are only mildly subjectively stimulating. -->

There are also more indirect [[mechanism of action|mechanisms of action]] by which a drug can elicit activating effects. Caffeine is an [[adenosine receptor antagonist]], and only indirectly increases catecholamine transmission in the brain.<ref name="National Academies Press (US)-2001">{{cite book|title=Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations.|publisher=National Academies Press (US)|location=Washington (DC)|url=https://www.ncbi.nlm.nih.gov/books/NBK223808/|language=en|url-status=live|archive-url=https://web.archive.org/web/20171009140913/https://www.ncbi.nlm.nih.gov/books/NBK223808/|archive-date=9 October 2017|year=2001}}</ref> [[Pitolisant]] is an [[H3 receptor antagonist|histamine 3 (H<sub>3</sub>)-receptor inverse agonist]]. As [[Histamine H3 receptor|histamine 3 (H<sub>3</sub>) receptors]] mainly act as [[autoreceptor]]s, pitolisant decreases negative feedback to [[histamine]]rgic neurons, enhancing histaminergic transmission.

The precise [[mechanism of action]] of some stimulants, such as modafinil, for treating symptoms of narcolepsy and other sleep disorders, remains unknown.<ref name="DrugsMonographForProfessionals">{{cite web |title=Modafinil Monograph for Professionals |url=https://www.drugs.com/monograph/modafinil.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=24 June 2018 |archive-date=30 March 2019 |archive-url=https://web.archive.org/web/20190330181813/https://www.drugs.com/monograph/modafinil.html |url-status=live }}</ref><ref name="pmid32032921">{{cite journal | vauthors = Thorpy MJ, Bogan RK | title = Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications | journal = Sleep Medicine | volume = 68 | issue = | pages = 97–109 | date = April 2020 | pmid = 32032921 | doi = 10.1016/j.sleep.2019.09.001 | s2cid = 203405397 }}</ref><ref name="Stahl-2017">{{cite book | vauthors=Stahl SM | title=Prescriber's Guide: Stahl's Essential Psychopharmacology | date=March 2017 | publisher=Cambridge University Press | location=Cambridge, United Kingdom | isbn=978-1-108-22874-9 | pages=491–495 | edition=6th | chapter=Modafinil }}</ref><ref name="pmid19300566">{{cite journal | vauthors = Gerrard P, Malcolm R | title = Mechanisms of modafinil: A review of current research | journal = Neuropsychiatric Disease and Treatment | volume = 3 | issue = 3 | pages = 349–364 | date = June 2007 | pmid = 19300566 | pmc = 2654794 }}</ref><ref name="pmid28646346">{{cite journal | vauthors = Lazarus M, Chen JF, Huang ZL, Urade Y, Fredholm BB | title = Adenosine and Sleep | journal = Handbook of Experimental Pharmacology | volume = 253 | issue = | pages = 359–381 | date = 2019 | pmid = 28646346 | doi = 10.1007/164_2017_36 | isbn = 978-3-030-11270-7 }}</ref>