{{MCN|date=April 2024}} {{Short description|Typical antipsychotic medication}} {{Drugbox | Watchedfields = changed | verifiedrevid = 462249027 | IUPAC_name = 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfinylphenothiazine | image = Mesoridazine.svg | image_class = skin-invert-image
<!--Clinical data--> | tradename = Serentil | Drugs.com = {{drugs.com|CONS|mesoridazine}} | MedlinePlus = a682306 | pregnancy_US = N | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_BR = C1 | legal_BR_comment = <ref>{{Cite web |last=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=Diário Oficial da União |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 = Rx-only | routes_of_administration = Oral, intravenous | class = Typical antipsychotic
<!--Pharmacokinetic data--> | bioavailability = | protein_bound = 4% | metabolism = Hepatic/renal | elimination_half-life = 24 to 48 hours | excretion = Biliary and renal
<!--Identifiers--> | IUPHAR_ligand = 7227 | CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 5588-33-0 | ATC_prefix = N05 | ATC_suffix = AC03 | ATC_supplemental = | PubChem = 4078 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00933 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 3936 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 5XE4NWM740 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D02671 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 6780 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1088
<!--Chemical data--> | C=21 | H=26 | N=2 | O=1 | S=2 | smiles = O=S(c2cc1N(c3c(Sc1cc2)cccc3)CCC4N(C)CCCC4)C | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C21H26N2OS2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(26(2)24)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = SLVMESMUVMCQIY-UHFFFAOYSA-N | melting_point = 130 | solubility = insoluble }}
'''Mesoridazine''' ('''Serentil''') is a phenothiazine class drug that is used in the treatment of schizophrenia.<ref name="pmid7031039">{{Cite journal |vauthors=Gershon S, Sakalis G, Bowers PA |date=December 1981 |title=Mesoridazine -- a pharmacodynamic and pharmacokinetic profile |journal=The Journal of Clinical Psychiatry |volume=42 |issue=12 |pages=463–9 |pmid=7031039}}</ref> It is one of the active metabolites of thioridazine. The drug's name is derived from the '''me'''thyl'''s'''ulf'''o'''xy and pipe'''rid'''ine functional groups in its chemical structure.
It has central antiadrenergic, antidopaminergic, antiserotonergic and weak muscarinic anticholinergic effects.
Serious side effects include akathisia, tardive dyskinesia and the potentially fatal neuroleptic malignant syndrome.
Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram.<ref>{{Cite web |last=American Society of Health-System Pharmacists (AHFS) |title=Mesoridazine |url=https://www.medlineplus.gov/druginfo/meds/a682306.html |website=Medline Plus |publisher=U.S. National Library of Medicine}}</ref>
Mesoridazine is on the FDA's Discontinued Drug Product List.<ref>{{Cite web | last=Food and Drug Administration |title=Determination That SERENTIL (Mesoridazine Besylate) Tablets, 10 Milligrams, 25 Milligrams, 50 Milligrams, and 100 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness |url=https://www.federalregister.gov/documents/2021/04/01/2021-06722/determination-that-serentil-mesoridazine-besylate-tablets-10-milligrams-25-milligrams-50-milligrams |website=National Register |date=April 2021 |publisher=U.S. Government}}</ref>
==Synthesis== [[File:Mesoridazine synthesis.svg|class=skin-invert-image|thumb|center|500px|[https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-13-0069 Thieme] Synthesis:<ref>Bourquin, J.-P.; Schwarb, G.; Gamboni, G.; Fischer, R.; Ruesch, L.; Guldimann, S.; Theus, V.; Schenker, E.; Renz, J. (1958). "Synthesen auf dem Phenothiazin-Gebiet. 1. Mitteilung. Mercaptophenothiazin-Derivate". Helvetica Chimica Acta. 41 (4): 1061–1072. doi:10.1002/hlca.19580410419.</ref><ref>Bourquin, J.-P.; Schwarb, G.; Gamboni, G.; Fischer, R.; Ruesch, L.; Guldimann, S.; Theus, V.; Schenker, E.; Renz, J. (1958). "Synthesen auf dem Phenothiazin-Gebiet. 2. Mitteilung. N-substituierte Mercaptophenothiazin-Derivate". Helvetica Chimica Acta. 41 (4): 1072–1108. doi:10.1002/hlca.19580410420.</ref> Patent:<ref>Schwarb Gustav, Renz Jany, Bourquin Jean-Pierre, {{US patent|3084161}} (1963 to Sandoz Ltd).</ref>]]
2-Methylthiophenothiazine [7643-08-5] ('''1''') is treated with acetic anhydride] to give the protected amide, ie 10-acetyl-2-methylthiophenothiazine, [https://pubchem.ncbi.nlm.nih.gov/compound/69367526 CID:69367526]. Oxidation of this by means of hydrogen peroxide and removal of the acetyl protecting group with potassium carbonate in methanol solution gives 2-methylsulfonylphenothiazine [23503-68-6] ('''3'''). Introduction of the sidechain by alkylation with 2-(2-chlorethyl)-1-methylpiperidine [50846-01-0] ('''6''') in the presence of sodamide, afforded the desired mesoridazine ('''5''').
== References == {{Reflist}}
{{Antipsychotics}} {{Navboxes | title = Pharmacodynamics | titlestyle = background:#ccccff | list1 = {{Adrenergic receptor modulators}} {{Dopamine receptor modulators}} {{Histamine receptor modulators}} {{Muscarinic acetylcholine receptor modulators}} {{Serotonin receptor modulators}} }} {{Tricyclics}}
Category:M1 receptor antagonists Category:M2 receptor antagonists Category:M3 receptor antagonists Category:M4 receptor antagonists Category:M5 receptor antagonists Category:Phenothiazines Category:Piperidines Category:Sulfoxides Category:Tertiary amines Category:Typical antipsychotics Category:Withdrawn drugs