Editing Stimulant (section)

===Pitolisant===
{{Main|Pitolisant}}

Pitolisant is an [[inverse agonist]] (antagonist) of the [[Histamine H3 receptor|histamine 3 (H<sub>3</sub>) autoreceptor]]. As such, pitolisant is an [[Antihistamine|antihistamine medication]] that also belongs to the class of CNS stimulants.<ref name="www.ncbi.nlm.nih.gov">{{cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK573784/|title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|chapter=Pitolisant|date=24 January 2012|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|via=PubMed|pmid=34516055|access-date=24 January 2024|archive-date=14 November 2023|archive-url=https://web.archive.org/web/20231114161839/https://www.ncbi.nlm.nih.gov/books/NBK573784/|url-status=live}}</ref><ref name="pmid31644012">{{cite book|url=http://www.ncbi.nlm.nih.gov/books/NBK548702/|title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|chapter=Central Nervous System (CNS) Stimulants|date=22 January 2012|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|via=PubMed|pmid=31644012|access-date=22 January 2024|archive-date=29 January 2023|archive-url=https://web.archive.org/web/20230129141034/https://www.ncbi.nlm.nih.gov/books/NBK548702/|url-status=live}}</ref><ref name="Drugs.com-pitolisant-side">{{cite web|url=https://www.drugs.com/mtm/pitolisant.html|title=Pitolisant Uses, Side Effects & Warnings|website=Drugs.com|access-date=22 January 2024|archive-date=19 January 2024|archive-url=https://web.archive.org/web/20240119024743/https://www.drugs.com/mtm/pitolisant.html|url-status=live}}</ref><ref name="Drugs.com-pitolisant-list-of CNS">{{cite web|url=https://www.drugs.com/drug-class/cns-stimulants.html|title=List of CNS stimulants + Uses & Side Effects|website=Drugs.com|access-date=22 January 2024|archive-date=6 January 2024|archive-url=https://web.archive.org/web/20240106222450/https://www.drugs.com/drug-class/cns-stimulants.html|url-status=live}}</ref> Pitolisant is also considered a medication of [[eugeroic]] class, which means that it promotes wakefulness and alertness. Pitolisant is the first [[wakefulness-promoting agent]] that acts by blocking the [[Histamine H3 receptor|H<sub>3</sub> autoreceptor]].<ref name="pmid31997137"/><ref name="pmid28449891"/><ref name="pmid34546302"/>

Pitolisant has been shown to be effective and well-tolerated for the treatment of [[narcolepsy]] with or without cataplexy.<ref name="pmid34546302">{{cite journal|title=Pitolisant (Wakix) for Narcolepsy|date=21 September 2021|journal=JAMA|volume=326|issue=11|pages=1060–1061|via=Silverchair|doi=10.1001/jama.2021.1349|pmid=34546302 |s2cid=237583921 }}</ref><ref name="pmid28449891">{{cite journal|title=The European Medicines Agency review of pitolisant for treatment of narcolepsy: summary of the scientific assessment by the Committee for Medicinal Products for Human Use|first1=Marta|last1=Kollb-Sielecka|first2=Pierre|last2=Demolis|first3=Joseph|last3=Emmerich|first4=Greg|last4=Markey|first5=Tomas|last5=Salmonson|first6=Manuel|last6=Haas|date=1 May 2017|journal=Sleep Medicine|volume=33|pages=125–129|via=Europe PMC|doi=10.1016/j.sleep.2017.01.002|pmid=28449891}}</ref><ref name="pmid31997137"/>

Pitolisant is the only non-controlled anti-narcoleptic drug in the [[United States|US]].<ref name="pmid31997137">{{cite journal |vauthors=Lamb YN |date=February 2020 |title=Pitolisant: A Review in Narcolepsy with or without Cataplexy |journal=CNS Drugs |volume=34 |issue=2 |pages=207–218 |doi=10.1007/s40263-020-00703-x |pmid=31997137 |s2cid=210949049}}</ref> It has shown minimal abuse risk in studies.<ref name="pmid31997137" /><ref name="pmid32941089">{{cite journal |vauthors=de Biase S, Pellitteri G, Gigli GL, Valente M |date=February 2021 |title=Evaluating pitolisant as a narcolepsy treatment option |journal=Expert Opinion on Pharmacotherapy |volume=22 |issue=2 |pages=155–162 |doi=10.1080/14656566.2020.1817387 |pmid=32941089 |s2cid=221788777}}</ref>

Blocking the [[Histamine H3 receptor|histamine 3 (H<sub>3</sub>) autoreceptor]] increases the activity of histamine [[neuron]]s in the brain. The H<sub>3</sub> autoreceptors regulate [[Histaminergic|histaminergic activity]] in the central nervous system (and to a lesser extent, the peripheral nervous system) by inhibiting [[histamine]] biosynthesis and release upon binding to endogenous histamine.<ref name="pmid2172771">{{cite journal | vauthors = West RE, Zweig A, Shih NY, Siegel MI, Egan RW, Clark MA | title = Identification of two H3-histamine receptor subtypes | journal = Molecular Pharmacology | volume = 38 | issue = 5 | pages = 610–613 | date = November 1990 | doi = 10.1016/S0026-895X(25)09479-9 | pmid = 2172771 | url = https://molpharm.aspetjournals.org/content/38/5/610 | access-date = 22 January 2024 | archive-date = 10 December 2023 | archive-url = https://web.archive.org/web/20231210105713/https://molpharm.aspetjournals.org/content/38/5/610 | url-status = live }}</ref> By preventing the binding of endogenous histamine at the H<sub>3</sub>, as well as producing a response opposite to that of endogenous histamine at the receptor (inverse agonism), pitolisant enhances histaminergic activity in the brain.<ref name="pmid35774905">{{cite journal | vauthors = Sarfraz N, Okuampa D, Hansen H, Alvarez M, Cornett EM, Kakazu J, Kaye AM, Kaye AD | display-authors = 6 | title = pitolisant, a novel histamine-3 receptor competitive antagonist, and inverse agonist, in the treatment of excessive daytime sleepiness in adult patients with narcolepsy | journal = Health Psychology Research | volume = 10 | issue = 3 | page = 34222 | date = 30 May 2022 | pmid = 35774905 | pmc = 9239364 | doi = 10.52965/001c.34222 }}</ref>