Editing Chlorpromazine (section)

==History==
[[File:Thorazine advert.jpg|thumb|Advertisement for Thorazine (chlorpromazine) from the early 1960s<ref>{{cite web| url=https://commons.wikimedia.org/wiki/File:Thorazine_advert.jpg#/media/File:Thorazine_advert.jpg |title= Thorazine advertisement| publisher= Smith Kline & French | year= c. 1963| quote=When the patient lashes out against 'them' –  Thorazine (brand of chlorpromazine) quickly puts an end to his violent outburst. 'Thorazine' is especially effective when the psychotic episode is triggered by delusions or hallucinations. At the outset of treatment, Thorazine's combination of antipsychotic and sedative effects provides both emotional and physical calming. Assaultive or destructive behavior is rapidly controlled. As therapy continues, the initial sedative effect gradually disappears. However, the antipsychotic effect continues, helping to dispel or modify delusions, hallucinations, and confusion while keeping the patient calm and approachable. Smith Kline and French Laboratories}}</ref>]]

In 1933, the French pharmaceutical company [[Laboratoires Rhône-Poulenc]] began to search for new [[antihistamine]]s. In 1947, it synthesized [[promethazine]], a [[phenothiazine]] derivative, which was found to have more pronounced sedative and antihistaminic effects than earlier drugs.<ref name = "Healy_2004">{{Cite book | vauthors = Healy D |title = The creation of psychopharmacology |year = 2004 |publisher = Harvard University Press |isbn = 978-0-674-01599-9 |page = 77 |chapter = Explorations in a new world |url = https://books.google.com/books?id=6O2rPJnyhj0C |url-status = live |access-date = 26 November 2013 |archive-url = https://web.archive.org/web/20170908170912/https://books.google.com/books?id=6O2rPJnyhj0C&printsec=frontcover&dq=isbn=978-0-674-01599-9&cd=1 |archive-date = 8 September 2017}}</ref>{{rp|77}} A year later, the French surgeon Pierre Huguenard used promethazine together with [[pethidine]] as part of a cocktail to induce relaxation and indifference in surgical patients. Another surgeon, [[Henri Laborit]], believed the compound stabilized the central nervous system by causing "artificial hibernation" and described this state as "sedation without [[narcotic|narcosis]]". He suggested to Rhône-Poulenc that they develop a compound with better-stabilizing properties.<ref>{{Cite book| vauthors = Healy D | title=The creation of psychopharmacology| year=2004| publisher=Harvard University Press| isbn=978-0-674-01599-9| page=80| chapter=Explorations in a new world}}</ref> In December 1950, the chemist Paul Charpentier produced a series of compounds that included RP4560 or chlorpromazine.<ref name="history05"/>

Chlorpromazine was distributed for testing to physicians between April and August 1951. Laborit trialled the medicine at the [[Val-de-Grâce]] military hospital in Paris, using it as an anaesthetic booster in intravenous doses of 50 to 100&nbsp;mg in surgery patients and confirming it as the best drug to date in calming and reducing shock, with patients reporting improved well being afterward. He also noted its [[hypothermic]] effect and suggested it may induce artificial hibernation. Laborit thought this would allow the body to better tolerate major surgery by reducing [[circulatory shock | shock]], a novel idea at the time.<ref name="history05"/><!-- cites previous sentences -->

Following on, Laborit considered whether chlorpromazine may have a role in managing patients with severe [[burn]]s, [[Raynaud's phenomenon]], or psychiatric disorders. At the Villejuif Mental Hospital in November 1951, he and Montassut administered an [[intravenous]] dose to psychiatrist Cornelia Quarti, who was acting as a volunteer. Quarti noted the indifference but fainted upon getting up to go to the toilet, and so further testing was discontinued. ([[Orthostatic hypotension]] is a known side effect of chlorpromazine). Despite this, Laborit continued to push for testing in psychiatric patients during early 1952. Psychiatrists were reluctant initially, but on 19 January 1952, it was administered (alongside pethidine, [[pentothal]] and ECT) to Jacques Lh., a 24-year-old [[mania| manic]] patient, who responded dramatically; he was discharged after three weeks, having received 855&nbsp;mg of the drug in total.<ref name="history05"/><!-- cites previous four sentences -->

[[Pierre Deniker]] had heard about Laborit's work from his brother-in-law, who was a surgeon, and ordered chlorpromazine for a clinical trial at the [[Sainte-Anne Hospital Center]] in Paris where he was chief of the men's service.<ref name="history05"/> Together with the hospital director [[Jean Delay]], they published their first clinical trial in 1952, in which they treated thirty-eight [[psychosis|psychotic]] patients with daily injections of chlorpromazine without the use of other sedating agents.<ref name="Turner2007"/> The response was dramatic; treatment with chlorpromazine went beyond simple sedation, with patients showing improvements in [[cognition| thinking]] and [[emotion]]al behaviour.<ref name="healy1">{{Cite book |url=https://books.google.com/books?id=6O2rPJnyhj0C |title=The Creation of Psychopharmacology | vauthors = Healy D |year=2004 |publisher=Harvard University Press |pages=37–73 |isbn=978-0-674-01599-9 |url-status=live |access-date=26 November 2013 |archive-url=https://web.archive.org/web/20170908170912/https://books.google.com/books?id=6O2rPJnyhj0C&printsec=frontcover&dq=isbn=978-0-674-01599-9&cd=1#v=onepage&q=chlorpromazie |archive-date=8 September 2017}}</ref> They also found that doses higher than those used by Laborit were required, giving patients 75–100&nbsp;mg daily. Known colloquially as "Laborit's drug", chlorpromazine was released onto the market in 1953 by Rhône-Poulenc and given the trade name ''Largactil'', derived from ''large'' "broad" and ''acti*'' "activity".<ref name="history05"/>

Deniker then visited America, where the publication of their work alerted the American psychiatric community that the new treatment might represent a real breakthrough. Heinz Lehmann of the [[Douglas Hospital|Verdun Protestant Hospital]] in Montreal trialled it in seventy patients and also noted its striking effects, with patients' symptoms resolving after many years of unrelenting psychosis.<ref>{{Cite web| vauthors = Dronsfield A |title=Chlorpromazine - unlocks the saylum|url=https://edu.rsc.org/feature/chlorpromazine-unlocks-the-saylum/2020118.article|access-date=13 January 2022|website=RSC Education|language=en}}</ref> By 1954, chlorpromazine was being used in the United States to treat [[schizophrenia]], [[mania]], [[psychomotor agitation|psychomotor excitement]], and other [[psychosis|psychotic]] disorders.<ref name="GG">{{cite book | isbn = 978-0-07-162442-8 | title = [[Goodman and Gilman's The Pharmacological Basis of Therapeutics]] | edition = 12th | vauthors = Brunton L, Chabner B, Knollman B | year = 2010 | publisher = McGraw-Hill Professional | location = New York }}</ref><ref>{{Cite book| vauthors = Long JW |title=The Essential guide to prescription drugs| publisher= HarperPerennial| location= New York|year=1992|pages=321–25|isbn=978-0-06-271534-0}}</ref><ref>{{Cite journal| vauthors = Reines BP | year= 1990| title= The Relationship Between Laboratory and Clinical Studies in Psychopharmacologic Discovery| journal= Perspectives on Medical Research| volume= 2| publisher= Medical Research Modernization Society| url= http://www.curedisease.net/reports/Perspectives/vol_2_1990/PsycholDisc.html| url-status= live| access-date= 26 November 2013| archive-url= https://web.archive.org/web/20150907024721/http://www.curedisease.net/reports/Perspectives/vol_2_1990/PsycholDisc.html| archive-date= 7 September 2015}}</ref>
Rhône-Poulenc licensed chlorpromazine to Smith Kline & French (today's [[GlaxoSmithKline]]) in 1953. In 1955 it was approved in the United States for the treatment of emesis (vomiting). The effect of this drug in emptying [[psychiatric hospitals]] has been compared to that of [[penicillin]] on [[infectious disease]]s.<ref name="Turner2007">{{cite journal | vauthors = Turner T | title = Chlorpromazine: unlocking psychosis | journal = BMJ | volume = 334 | issue = Suppl 1 | pages = s7 | date = January 2007 | pmid = 17204765 | doi = 10.1136/bmj.39034.609074.94 | s2cid = 33739419 }}</ref> 

The popularity of the drug fell in the late 1960s as newer drugs came on the scene. From chlorpromazine several other similar antipsychotics were developed, leading to the discovery of [[antidepressants]].<ref name="healy3">{{Cite book| vauthors = Healy D | title= The Creation of Psychopharmacology| url= https://books.google.com/books?id=6O2rPJnyhj0C| year= 2004| publisher= Harvard University Press| isbn= 9780674015999| page= 2| chapter= Introduction| url-status= live| access-date= 26 November 2013| archive-url= https://web.archive.org/web/20170908170912/https://books.google.com/books?id=6O2rPJnyhj0C&printsec=frontcover&dq=isbn=978-0-674-01599-9&cd=1#v=onepage&q=chlorpromazine| archive-date= 8 September 2017}}</ref>

Chlorpromazine largely replaced [[electroconvulsive therapy]], [[hydrotherapy]],<ref>{{cite web |url= http://davidhealy.org/wp-content/uploads/2014/07/Psychopharmacology-and-The-Government-of-the-Self.pdf |title= Psychopharmacology and the Government of the Self | vauthors = Healy D |date= 2000 |website= davidhealy.org |access-date= 20 July 2015 |url-status= dead |archive-url= https://web.archive.org/web/20141006092443/http://davidhealy.org/wp-content/uploads/2014/07/Psychopharmacology-and-The-Government-of-the-Self.pdf |archive-date= 6 October 2014}}</ref> [[psychosurgery]], and [[insulin shock therapy]].<ref name="healy1"/> By 1964, about fifty million people worldwide had taken it.<ref>{{Cite web|url=https://www.pbs.org/wgbh/aso/databank/entries/dh52dr.html|title=Drug for treating schizophrenia identified|website=PBS.org|publisher=[[WGBH-TV]]|access-date=7 July 2010|url-status=live|archive-url=https://web.archive.org/web/20090918064700/http://www.pbs.org/wgbh/aso/databank/entries/dh52dr.html|archive-date=18 September 2009}}</ref> Chlorpromazine, in widespread use for fifty years, remains a "benchmark" drug in the treatment of [[schizophrenia]], an effective drug although not a perfect one.<ref name="Adams" />