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Revision as of 13:20, 10 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 468444172 of page Thioridazine for the Chem/Drugbox validation project (updated: '').		Latest revision as of 07:17, 21 December 2024 edit GreenC bot (talk | contribs)Bots2,546,166 edits Rescued 1 archive link; reformat 1 link. Wayback Medic 2.5 per WP:USURPURL and JUDI batch #20
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			{{Short description|Typical antipsychotic medication}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{Redirect|Aldazine|functional group|Aldazines}}
	{{drugbox | Verifiedfields = changed
			{{Distinguish|Thorazine}}
	| Watchedfields = changed
			{{Lead too short|date=September 2021}}
	| verifiedrevid = 416502199
			{{Use dmy dates|date=July 2020}}
	| IUPAC_name = 10-{2-ethyl}-<BR>2-methylsulfanylphenothiazine
			{{Infobox drug
	| image = Thioridazine-2D-skeletal.png
			| verifiedrevid = 470608946
	| width = 175
			| IUPAC_name = 10-{2-ethyl}-<br />2-methylsulfanylphenothiazine
	| image2 = Thioridazine3d.png
			| image = Thioridazine.svg
			| width = 200px
	<!--Clinical data-->		<!--Clinical data-->
	| Drugs.com = {{drugs.com|CDI|thioridazine}}		| Drugs.com = {{drugs.com|ppa|thioridazine}}
	| MedlinePlus = a682119		| MedlinePlus = a682119
			| DailyMedID = Thioridazine
	| pregnancy_category = Only if clearly needed
			| licence_US = Thioridazine
	| legal_status = RX-only-medication, non-narcotic
			| pregnancy_AU = C
	| routes_of_administration = oral (tablets, concentration, sometimes syrup)
			| pregnancy_US = N
			| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
			| legal_BR = C1
			| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=] |language=pt-BR |publication-date=2023-04-04}}</ref>
			| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
			| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
			| legal_NZ = <!-- Class A, B, C -->
			| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
			| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
			| legal_EU =
			| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
			| legal_status = Withdrawn by the manufacturer worldwide;<ref name = NHS/> generic formulations are still available by prescription
			| routes_of_administration = Oral
			| class = ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = incomplete		| bioavailability = Incomplete
	| metabolism = hepatic		| metabolism = Hepatic (at least partly mediated by ])
			| elimination_half-life = 21–24 hours<ref>{{cite journal | vauthors = Shvartsburd A, Sajadi C, Morton V, Mirabi M, Gordon J, Smith RC | title = Blood levels of haloperidol and thioridazine during maintenance neuroleptic treatment of schizophrenic outpatients | journal = Journal of Clinical Psychopharmacology | volume = 4 | issue = 4 | pages = 194–198 | date = August 1984 | pmid = 6470190 | doi = 10.1097/00004714-198408000-00004 | s2cid = 33161119 }}</ref>
	| elimination_half-life = 7–13 hours (up to 20 hours)
	| excretion = feces		| excretion = Feces
	<!--Identifiers-->		<!--Identifiers-->
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 50-52-2		| CAS_number = 50-52-2
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	| ATC_suffix = AC02		| ATC_suffix = AC02
	| PubChem = 5452		| PubChem = 5452
			| PubChemSubstance = 148555
	| IUPHAR_ligand = 100		| IUPHAR_ligand = 100
	| DrugBank_Ref = {{drugbankcite|changed|drugbank}}		| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| DrugBank = DB00679		| DrugBank = DB00679
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
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	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D00373		| KEGG = D00373
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 9566		| ChEBI = 9566
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 479		| ChEMBL = 479
			| synonyms =
	<!--Chemical data-->		<!--Chemical data-->
	| C=21 | H=26 | N=2 | S=2		| C=21 | H=26 | N=2 | S=2
			| SMILES = S(c2cc1N(c3c(Sc1cc2)cccc3)CCC4N(C)CCCC4)C
	| molecular_weight = 370.577
	| smiles = S(c2cc1N(c3c(Sc1cc2)cccc3)CCC4N(C)CCCC4)C
	| InChI = 1/C21H26N2S2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(24-2)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C21H26N2S2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(24-2)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3		| StdInChI = 1S/C21H26N2S2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(24-2)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3
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	| StdInChIKey = KLBQZWRITKRQQV-UHFFFAOYSA-N		| StdInChIKey = KLBQZWRITKRQQV-UHFFFAOYSA-N
	}}		}}
			'''Thioridazine''' ('''Mellaril''' or '''Melleril''') is a first generation ] ] belonging to the ] drug group and was previously widely used in the treatment of ] and ]. The branded product was withdrawn worldwide in 2005 because it caused severe cardiac arrhythmias. However, generic versions are still available in the US.<ref name = NHS/>
			==Indications==
			Thioridazine was voluntarily discontinued by its manufacturer, ], worldwide because it caused severe cardiac arrhythmias. However, generics remain on the market in some countries.<ref name=NHS>{{cite web|title=SHARED CARE PROTOCOL Thioridazine|work=NHS Lothian Joint Formulary|date=March 2012|url=http://www.ljf.scot.nhs.uk/SharedCareofMedicines/Shared%20Care%20Agreements/SCA/SCA%20Thioridazine%20v1%200%20Final.pdf|url-status=dead|archive-url=https://web.archive.org/web/20150518080549/http://www.ljf.scot.nhs.uk/SharedCareofMedicines/Shared%20Care%20Agreements/SCA/SCA%20Thioridazine%20v1%200%20Final.pdf|archive-date=18 May 2015}}</ref><ref name=PDS2012>{{cite journal | vauthors = Purhonen M, Koponen H, Tiihonen J, Tanskanen A | title = Outcome of patients after market withdrawal of thioridazine: a retrospective analysis in a nationwide cohort | journal = Pharmacoepidemiology and Drug Safety | volume = 21 | issue = 11 | pages = 1227–1231 | date = November 2012 | pmid = 22941581 | doi = 10.1002/pds.3346 | s2cid = 19560432 }}</ref><ref>{{cite news|title=WHO Pharmaceuticals Newsletter 2005, No. 04: REGULATORY MATTERS: Thioridazine - Sale discontinued in Canada|date=2005|work=Essential Medicines and Health Products Information Portal|publisher=World Health Organization|url=http://apps.who.int/medicinedocs/en/d/Js8119e/1.12.html|archive-url=https://web.archive.org/web/20110528180405/http://apps.who.int/medicinedocs/en/d/Js8119e/1.12.html|url-status=dead|archive-date=28 May 2011|access-date=28 October 2013|volume=4|issue=2|page=5}}</ref><ref>{{cite magazine|title=Withdrawal of thioridazine|journal=Australian Prescriber|volume=30|issue=3|page=82|url=http://www.australianprescriber.com/magazine/30/3/article/891.pdf|archive-url=https://web.archive.org/web/20130723103135/http://www.australianprescriber.com/magazine/30/3/article/891.pdf|url-status=usurped|archive-date=23 July 2013|date=June 2007}}</ref>
			Its primary use in medicine is for the treatment of schizophrenia.<ref name = GG>{{cite book | veditors = Brunton LL, Chabner B, Knollmann BC |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics |edition=12th |location=New York |publisher=McGraw-Hill |year=2011 |isbn=978-0-07-162442-8|title-link=Goodman & Gilman's The Pharmacological Basis of Therapeutics }}</ref> It was also tried with some success as a treatment for various psychiatric symptoms seen in people with dementia,<ref>{{cite journal | vauthors = Kirchner V, Kelly CA, Harvey RJ | title = Thioridazine for dementia | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD000464 | date = 2001 | pmid = 11686961 | pmc = 7034526 | doi = 10.1002/14651858.CD000464 }}</ref> but chronic use of thioridazine and other anti-psychotics in people with dementia is not recommended.<ref>{{cite journal | vauthors = Declercq T, Petrovic M, Azermai M, Vander Stichele R, De Sutter AI, van Driel ML, Christiaens T | title = Withdrawal versus continuation of chronic antipsychotic drugs for behavioural and psychological symptoms in older people with dementia | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD007726 | date = March 2013 | pmid = 23543555 | doi = 10.1002/14651858.CD007726.pub2 | hdl-access = free | hdl = 1854/LU-3109108 }}</ref>
			Generic forms of thioridazine remain on the market in a few countries, usually with restrictions due to the risk of arrhythmias. For example, in the US, it is restricted to patients who have taken at least 2 other antipsychotics that either failed or caused serious side effects.<ref name="medlineplus.gov">{{cite web |title=Thioridazine: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a682119.html |website=medlineplus.gov |access-date=7 June 2023 |language=en}}</ref>
			==Side effects==
			{{further information|Phenothiazine}}
			Thioridazine prolongs the ] in a dose-dependent manner.<ref name = DM>{{cite web|title=THIORIDAZINE HYDROCHLORIDE tablet, film coated |work=DailyMed|publisher=Mutual Pharmaceutical|date=September 2010|access-date=28 October 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9c4bedb4-2d59-4fcd-aad7-fce988cd96d8}}</ref> It produces significantly less ] than most first-generation antipsychotics, likely due to its potent anticholinergic effect.<ref>{{cite journal | vauthors = Fenton M, Rathbone J, Reilly J, Sultana A | title = Thioridazine for schizophrenia | journal = The Cochrane Database of Systematic Reviews | volume = 2007 | issue = 3 | pages = CD001944 | date = July 2007 | pmid = 17636691 | pmc = 6718212 | doi = 10.1002/14651858.CD001944.pub2 }}</ref><ref>{{cite journal | vauthors = Keks N, McGrath J, Lambert T, Catts S, Vaddadi K, Burrows G, Varghese F, George T, Hustig H, Burnett P | display-authors = 6 | title = The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia | journal = Acta Psychiatrica Scandinavica | volume = 90 | issue = 5 | pages = 358–365 | date = November 1994 | pmid = 7872041 | doi = 10.1111/j.1600-0447.1994.tb01607.x | s2cid = 40042606 }}</ref> Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies (specifically retinitis pigmentosa).<ref>{{cite journal | vauthors = Fornaro P, Calabria G, Corallo G, Picotti GB | title = Pathogenesis of degenerative retinopathies induced by thioridazine and other antipsychotics: a dopamine hypothesis | journal = Documenta Ophthalmologica. Advances in Ophthalmology | volume = 105 | issue = 1 | pages = 41–49 | date = July 2002 | pmid = 12152801 | doi = 10.1023/A:1015768114192 | s2cid = 23618581 }}</ref> It has a higher propensity for causing ] side effects coupled with a lower propensity for causing ] and sedation than ], but also has a higher incidence of hypotension and cardiotoxicity.<ref>{{cite web|title=Martindale: The Complete Drug Reference|date=18 August 2010|access-date=28 October 2013|work=Medicines Complete|publisher=The Pharmaceutical Press|url=https://www.medicinescomplete.com/mc/martindale/current/login.htm?uri=http%3A%2F%2Fwww.medicinescomplete.com%2Fmc%2Fmartindale%2Fcurrent%2F}}</ref> It is also known to possess a relatively high liability for causing ] compared to other antipsychotics. Similarly to other first-generation antipsychotics it has a relatively high liability for causing prolactin elevation. It is moderate risk for causing weight gain.<ref name = UpToDate>{{cite web|title=Selected adverse effects of antipsychotic medications for schizophrenia|work=UpToDate|publisher=Wolters Kluwer Health|access-date=24 October 2013|url=http://www.uptodate.com/contents/pharmacotherapy-for-schizophrenia-side-effect-management?detectedLanguage=en&source=search_result&search=Selected+adverse+effects+of+antipsychotic+medications+for+schizophrenia&selectedTitle=1%7E150&provider=noProvider#subscribeMessage}}</ref> As with all antipsychotics thioridazine has been linked to cases of ] (an often permanent neurological disorder characterised by slow, repetitive, purposeless and involuntary movements, most often of the facial muscles, that is usually brought on by years of continued treatment with antipsychotics, especially the first-generation (or ''typical'') antipsychotics such as thioridazine) and ] (a potentially fatal complication of antipsychotic treatment).<ref name = DM/> Blood dyscrasias such as ], ] and ] are possible with thioridazine treatment.<ref name = DM/> Thioridazine is also associated with abnormal retinal pigmentation after many years of use.<ref>{{cite journal | vauthors = Scott AW | title = Retinal Pigmentation in a Patient Receiving Thioridazine | journal = Archives of Ophthalmology | volume = 70 | issue = 6 | pages = 775–778 | date = December 1963 | pmid = 14065014 | doi = 10.1001/archopht.1963.00960050777009 }}</ref>
			Thioridazine has been correlated to rare instances of clinically apparent acute cholestatic liver injury.<ref>{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/n/livertox/Thioridazine/|title=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|chapter=Thioridazine|year=2012|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31643669 }}</ref>
			==Pharmacology==
			Thioridazine has the following binding profile:<ref>{{cite web | title = PDSP K<sub>i</sub> Database | work = Psychoactive Drug Screening Program (PDSP)|author1-link=Bryan Roth | vauthors = Roth BL, Driscol J | url = http://pdsp.med.unc.edu/pdsp.php | publisher = University of North Carolina at Chapel Hill and the United States National Institute of Mental Health | access-date = 28 October 2013 | date = 12 January 2011 | url-status = dead | archive-url = https://web.archive.org/web/20131108013656/http://pdsp.med.unc.edu/pdsp.php | archive-date = 8 November 2013}}</ref>
			{| class="wikitable"
			|-
			! Biologic Protein !! Binding affinity (K<sub>i</sub>) !! Binding affinity of ] (K<sub>i</sub> ) !! Binding affinity of ] (K<sub>i</sub> ) !! Notes
			|-
			| ] || 1259 || ND || ND ||
			|-
			| ] || 842 || ND || ND ||
			|-
			| ] || 1684 || ND || ND ||
			|-
			| ] || 144.35 || 500 (HB) || ND ||
			|-
			| ] || 109 || ND || ND ||
			|-
			| ] || 579 || ND|| ND ||
			|-
			| ] || 194 || ND || ND ||
			|-
			| ] || 27.67 || 4.76 (HB)|| ND || The ratio of 5-HT2A to D2 receptor binding is believed to dictate whether or not most antipsychotics are ] or ]. In thioridazine's case its ratio of 5-HT2A to D2 receptor binding is below the level that's believed to be required for ''atypicality'' despite its relatively low extrapyramidal side effect liability in practice.<ref name = GG/>
			|-
			| ] || 53 || 157 || ND || Believed to play a role in the weight gain-promoting effects of antipsychotics.<ref name = GG/>
			|-
			| ] || >10000 || ND || ND ||
			|-
			| ] || 364 || ND || ND ||
			|-
			| ] || 57.05 || 380 || ND ||
			|-
			| ] || 99 || 73 (RC) || ND ||
			|-
			| ] || 3.15 || 2 (HB) || ND || Likely the receptor responsible for the ] known to occur in individuals on thioridazine.<ref name = GG/>
			|-
			| ] || 2.4 || ND || ND ||
			|-
			| ] || 134.15 || 1612.9 (HB) || ND ||
			|-
			| ] || 341.65 || ND || ND ||
			|-
			| ] || 74.9 || ND || ND ||
			|-
			| ] || >10000 || ND || ND ||
			|-
			| ] || >10000 || ND || ND ||
			|-
			| ] || 12.8 || 10 || ND || This receptor is believed to be the chief receptor responsible for the ] side effects of thioridazine (e.g. dry mouth, constipation, blurred vision, etc.). Likely plays a role in thioridazine's low extrapyramidal side effect liability as anticholinergic drugs such as ] are routinely given to treat ] resulting from antipsychotic treatment.<ref name = GG/>
			|-
			| ] || 286.33 || 15 || ND ||
			|-
			| ] || 29 || 90 || ND ||
			|-
			| ] || 310.33 || 19 || ND ||
			|-
			| ] || 12.67 || 60 || ND ||
			|-
			| ] || 94.5 || ND || ND ||
			|-
			| ] || 0.4 || 4.3 || 0.25 || Believed to be the receptor responsible for the therapeutic effects of antipsychotics.<ref name = GG/>
			|-
			| ] || 1.5 || 2.6 || 0.7 ||
			|-
			| ] || 1.5 || 9.1 || ND ||
			|-
			| ] || 258 || ND || ND ||
			|-
			| ] || 191 || ND|| ND || Likely involved in thioridazine's cardiac effects.
			|-
			| ] || 16.5 || 1.81 (HB) || ND || Likely responsible for the sedating effects of thioridazine.
			|-
			| ] || 136 || ND || ND || Regulates the release of ] into the ].
			|-
			| ] || 2400 || ND || ND ||
			|}
			''Note: The Binding affinities given are towards cloned human receptors unless otherwise specified''
			'''Acronyms used'''<br>
			HB – Human brain receptor<br>
			RC – Cloned rat receptor<br>
			ND – No data
			==Metabolism==
			Thioridazine is a ] compound with two ]s, both of which are metabolized, according to Eap et al., by ] into (''S'')- and (''R'')-thioridazine-2-sulfoxide, better known as ],<ref> National Center for Biotechnology Information.</ref> and into (''S'')- and (''R'')-thioridazine-5-sulfoxide.<ref>{{cite journal | vauthors = Eap CB, Guentert TW, Schãublin-Loidl M, Stabl M, Koeb L, Powell K, Baumann P | title = Plasma levels of the enantiomers of thioridazine, thioridazine 2-sulfoxide, thioridazine 2-sulfone, and thioridazine 5-sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin | journal = Clinical Pharmacology and Therapeutics | volume = 59 | issue = 3 | pages = 322–331 | date = March 1996 | pmid = 8653995 | doi = 10.1016/S0009-9236(96)80010-5 | s2cid = 45135063 }}</ref> Mesoridazine is in turn metabolized into ].<ref> National Center for Biotechnology Information.</ref> Thioridazine is an inhibitor of ] and CYP3A4.<ref>{{cite journal | vauthors = Daniel WA, Syrek M, Ryłko Z, Kot M | title = Effects of phenothiazine neuroleptics on the rate of caffeine demethylation and hydroxylation in the rat liver | journal = Polish Journal of Pharmacology | volume = 53 | issue = 6 | pages = 615–621 | year = 2001 | pmid = 11985335 | url = http://www.if-pan.krakow.pl/pjp/pdf/2001/6_615.pdf }}</ref>
			==History==
			The manufacturer ]/Sandoz/Wander of the brands of thioridazine, Mellaril in the US and Canada and Melleril in Europe, discontinued the drug worldwide in June 2005.<ref name = NHS/><ref name=PDS2012/>
			Generic forms of thioridazine however remain on the market in a few countries usually with restrictions for example in the US its restricted to patients who have taken at least 2 other antipsychotics that either failed or caused serious side effects <ref name="medlineplus.gov"/>
			==Antibiotic activity==
			Thioridazine is known to kill ]<ref>{{cite journal | vauthors = Amaral L, Boeree MJ, Gillespie SH, Udwadia ZF, van Soolingen D | title = Thioridazine cures extensively drug-resistant tuberculosis (XDR-TB) and the need for global trials is now! | journal = International Journal of Antimicrobial Agents | volume = 35 | issue = 6 | pages = 524–526 | date = June 2010 | pmid = 20188526 | doi = 10.1016/j.ijantimicag.2009.12.019 | url = https://hal.archives-ouvertes.fr/hal-00585817/file/PEER_stage2_10.1016%252Fj.ijantimicag.2009.12.019.pdf }}</ref><ref name = XDR>{{cite journal | vauthors = Amaral L, Viveiros M | title = Why thioridazine in combination with antibiotics cures extensively drug-resistant Mycobacterium tuberculosis infections | journal = International Journal of Antimicrobial Agents | volume = 39 | issue = 5 | pages = 376–380 | date = May 2012 | pmid = 22445204 | doi = 10.1016/j.ijantimicag.2012.01.012 }}</ref> and to make ] '']'' sensitive to ].<ref>{{cite journal | vauthors = Thanacoody HK | title = Thioridazine: resurrection as an antimicrobial agent? | journal = British Journal of Clinical Pharmacology | volume = 64 | issue = 5 | pages = 566–574 | date = November 2007 | pmid = 17764469 | pmc = 2203271 | doi = 10.1111/j.1365-2125.2007.03021.x }}</ref><ref>{{cite journal | vauthors = Thorsing M, Klitgaard JK, Atilano ML, Skov MN, Kolmos HJ, Filipe SR, Kallipolitis BH | title = Thioridazine induces major changes in global gene expression and cell wall composition in methicillin-resistant Staphylococcus aureus USA300 | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e64518 | date = May 2013 | pmid = 23691239 | pmc = 3656896 | doi = 10.1371/journal.pone.0064518 | doi-access = free | bibcode = 2013PLoSO...864518T }}</ref> A possible mechanism of action for the drug's antibiotic activity is via the inhibition of ]. The β-lactam antibiotic resistance is due to the secretion ] a protein that destroys antibiotics. If the bacteria cannot secrete the β-lactamase, then the antibiotic will be effective.<ref name = XDR/> The drug has been successfully used in the treatment of ] in conjunction with more conventional ].
			==Synthesis==
			Note: Same sidechain used for ] and ].
			Synthesis:<ref>{{cite journal | vauthors = Bourquin JP, Schwarb G, Gamboni G, Fischer R, Ruesch L, Guldimann S, Theus V, Schenker E, Renz J | date = 1958 | title = Synthesen auf dem Phenothiazin-Gebiet. 2. Mitteilung. N-substituierte Mercaptophenothiazin-Derivate | journal = Helvetica Chimica Acta | volume = 41 | issue = 4 | pages = 1072–1108 | doi = 10.1002/hlca.19580410420 }}</ref> Patent:<ref>{{cite patent | inventor = Renz J, Bourquin JP | title = Phenothiazine derivatives substituted by a monovalent sulfur function in 3-position | url = https://patents.google.com/patent/US3239514A/en?oq=US+3239514 | country = US | number = 3239514 | gdate = 1966 | assign1 = Sandoz KK }}</ref> Sidechain:<ref name="pmid20994984">{{cite journal | vauthors = Norton TR, Seibert RA, Benson AA, Bergstrom FW | title = The synthesis of some substituted 8-aminoquinolines | journal = Journal of the American Chemical Society | volume = 68 | issue = 8| pages = 1572–6 | date = August 1946 | pmid = 20994984 | doi = 10.1021/ja01212a058 | bibcode = 1946JAChS..68.1572N }}</ref> Enantiomers:<ref>{{cite journal | vauthors = Antonsen SG, Monsen EB, Ovchinnikov K, Nolsøe JM, Ekeberg D, Kristiansen JE, Diep DB, Stenstrøm YH | title = Synthesis of the enantiomers of thioridazine. | journal = SynOpen | date = 2020 | volume = 4 | issue = 1 | pages = 12–16 | doi = 10.1055/s-0039-1690834 | doi-access = free }}</ref>]]
			The alkylation of 2-Picoline ('''1''') with formaldehyde gives 2-Pyridineethanol ('''2'''). Forming the quat salt with methyl iodide leads to 2-(2-hydroxyethyl)-1-methyl-pyridinium iodide ('''3'''). Catalytic hydrogenation in the presence of hydrochloric acid leads to 2-(2-Chloroethyl)-1-Methylpiperidine ('''4'''). Alkylation of 2-Methylthiophenothiazine ('''5''') in the presence of sodium hydride base completed the synthesis of ''Thioridazine'' ('''6''').
			== References ==
			{{Reflist}}
			== Further reading ==
			{{refbegin}}
			* {{cite book | vauthors = Dean L | chapter=Thioridazine Therapy and CYP2D6 Genotypes | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK424018/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | title=Medical Genetics Summaries | publisher=] (NCBI) | year=2017 | pmid=28520378 | id=Bookshelf ID: NBK424018 | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}
			{{refend}}
			== External links ==
			* {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/thioridazine | publisher = U.S. National Library of Medicine| work = Drug Information Portal | title = Thioridazine }}
			* ''Schizophrenia Daily News Blog.''
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