Mesoridazine

Mesoridazine
Clinical data
Trade names	Serentil
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a682306
Routes of; administration	Oral, intravenous
Drug class	Typical antipsychotic
ATC code	N05AC03 (WHO) ;
Legal status
Legal status	BR: Class C1 (Other controlled substances); In general: ℞ (Prescription only);
Pharmacokinetic data
Protein binding	4%
Metabolism	Hepatic/renal
Elimination half-life	24 to 48 hours
Excretion	Biliary and renal
Identifiers
	IUPAC name 10-[2-(1-methylpiperidin-2-yl)ethyl]-2-methylsulfinylphenothiazine;
CAS Number	5588-33-0 ;
PubChem CID	4078;
IUPHAR/BPS	7227;
DrugBank	DB00933 ;
ChemSpider	3936 ;
UNII	5XE4NWM740;
KEGG	D02671 ;
ChEBI	CHEBI:6780 ;
ChEMBL	ChEMBL1088 ;
CompTox Dashboard (EPA)	DTXSID3023265 ;
Chemical and physical data
Formula	C21H26N2OS2
Molar mass	386.57 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	130 °C (266 °F)
Solubility in water	insoluble mg/mL (20 °C)
	SMILES O=S(c2cc1N(c3c(Sc1cc2)cccc3)CCC4N(C)CCCC4)C;
	InChI InChI=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 ; Key:SLVMESMUVMCQIY-UHFFFAOYSA-N ;
	(verify)

Mesoridazine (Serentil) is a phenothiazine class drug that is used in the treatment of schizophrenia.^[2] It is one of the active metabolites of thioridazine. The drug's name is derived from the methylsulfoxy and piperidine 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Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram.^[3]

Mesoridazine is on the FDA's Discontinued Drug Product List.^[4]

Synthesis

Thieme Synthesis:^[5]^[6] Patent:^[7]

2-Methylthiophenothiazine [7643-08-5] (1) is treated with acetic anhydride] to give the protected amide, ie 10-acetyl-2-methylthiophenothiazine, 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

^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
^ Gershon S, Sakalis G, Bowers PA (December 1981). "Mesoridazine -- a pharmacodynamic and pharmacokinetic profile". The Journal of Clinical Psychiatry. 42 (12): 463–9. PMID 7031039.
^ American Society of Health-System Pharmacists (AHFS). "Mesoridazine". Medline Plus. U.S. National Library of Medicine.
^ Food and Drug Administration (April 2021). "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". National Register. U.S. Government.
^ 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.
^ 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.
^ Schwarb Gustav, Renz Jany, Bourquin Jean-Pierre, U.S. patent 3,084,161 (1963 to Sandoz Ltd).

[1] Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.

[pmid7031039-2] Gershon S, Sakalis G, Bowers PA (December 1981). "Mesoridazine -- a pharmacodynamic and pharmacokinetic profile". The Journal of Clinical Psychiatry. 42 (12): 463–9. PMID 7031039.

[3] American Society of Health-System Pharmacists (AHFS). "Mesoridazine". Medline Plus. U.S. National Library of Medicine.

[4] Food and Drug Administration (April 2021). "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". National Register. U.S. Government.

[5] 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.

[6] 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.

[7] Schwarb Gustav, Renz Jany, Bourquin Jean-Pierre, U.S. patent 3,084,161 (1963 to Sandoz Ltd).

[2]

[1]

[3]

[4]

[5]

[6]

[7]