MESORIDAZINE BESYLATE

Details

Stereochemistry	MIXED
Molecular Formula	C21H26N2OS2.C6H6O3S
Molecular Weight	544.749
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(=O)(=O)C1=CC=CC=C1.CN2CCCCC2CCN3C4=CC(=CC=C4SC5=C3C=CC=C5)[S+](C)[O-]

InChI

InChIKey=CRJHBCPQHRVYBS-UHFFFAOYSA-N

InChI=1S/C21H26N2OS2.C6H6O3S/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;7-10(8,9)6-4-2-1-3-5-6/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3;1-5H,(H,7,8,9)

HIDE SMILES / InChI

Molecular Formula	C6H6O3S
Molecular Weight	158.175
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C21H26N2OS2
Molecular Weight	386.574
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/16-774S073.pdf

Mesoridazine (brand name Serentil) is a phenothiazine antipsychotic. It was marketed in the U.S. for the treatment of schizophrenia, behavioral problems in mental deficiency and chronic brain syndrome, alcoholism and psychoneurotic symptoms, such as anxiety and tension. Due to the risk of serious cardiac events the indicated use of Serentil was limited to severely ill schizophrenic patients who fail other therapies. Based upon animal studies, mesoridazine acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. Mesoridazine shows a moderate adrenergic blocking activity in vitro and in vivo and antagonizes 5-hydroxytryptamine in vivo.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
D(2) dopamine receptor 58 Target ID: P14416 Gene ID: 1813.0 Gene Symbol: DRD2 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15357957	Antagonist 2778		3.0 nM [Ki]
5-hydroxytryptamine receptor 2A 69 Target ID: P28223 Gene ID: 3356.0 Gene Symbol: HTR2A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/15357957	Antagonist 2778

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/16-774S073.pdf	Primary		Approved 8429	SERENTIL Approved Use Indicated for treatment severely ill schizophrenic patients who have failed to respond adequately to treatment with other antipsychotic drugs Launch Date 4.9248E9
Psychosis 16 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/16-774S073.pdf	Primary		Approved 8429	SERENTIL Approved Use Psychosis Launch Date 4.9248E9

C_max

Value	Dose	Co-administered	Analyte	Population
240 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17410120/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MESORIDAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
2400 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17410120/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MESORIDAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17410120/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MESORIDAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
75% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17410120/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		MESORIDAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
3.1 g single, oral Overdose Dose: 3.1 g Route: oral Route: single Dose: 3.1 g Sources: https://pubmed.ncbi.nlm.nih.gov/3177997/	healthy, 20 years n = 1 Health Status: healthy Condition: suicide attempt Age Group: 20 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3177997/	Disc. AE: Ventricular arrhythmias and cardiac arrest... AEs leading to discontinuation/dose reduction: Ventricular arrhythmias and cardiac arrest (grade 4, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3177997/
16 ug/mL single, oral Overdose Dose: 16 ug/mL Route: oral Route: single Dose: 16 ug/mL Sources: https://pubmed.ncbi.nlm.nih.gov/3824877/	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: mentally retarded Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3824877/	Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/3824877/
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1140909/	healthy, 48-62 years n = 7 Health Status: healthy Age Group: 48-62 years Sex: unknown Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/1140909/	Sources: https://pubmed.ncbi.nlm.nih.gov/1140909/

AEs

AE	Significance	Dose	Population
Ventricular arrhythmias and cardiac arrest	grade 4, 1 patient Disc. AE	3.1 g single, oral Overdose Dose: 3.1 g Route: oral Route: single Dose: 3.1 g Sources: https://pubmed.ncbi.nlm.nih.gov/3177997/	healthy, 20 years n = 1 Health Status: healthy Condition: suicide attempt Age Group: 20 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3177997/
Death	grade 5, 1 patient Disc. AE	16 ug/mL single, oral Overdose Dose: 16 ug/mL Route: oral Route: single Dose: 16 ug/mL Sources: https://pubmed.ncbi.nlm.nih.gov/3824877/	unhealthy, 23 years n = 1 Health Status: unhealthy Condition: mentally retarded Age Group: 23 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3824877/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://jpet.aspetjournals.org/content/jpet/365/2/336.full.pdf?with-ds=yes#page=4 Page: 4.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubmed.ncbi.nlm.nih.gov/14734057/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6780	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6780
ChemicalBook	CB0157447	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0157447
ChemicalBook	CB0875422	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0875422

PubMed

Title	Date	PubMed
Neuroleptics and neurologic reactions.	1973 Mar	4144147
Drug-induced dystonia.	1975 May	1119613
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.	1978 Oct 7	709472
Rapid death resulting from mesoridazine overdose.	1987 Feb	3824877
Complete heart block associated with mesoridazine and lithium combination.	1987 Mar	3102462
Cardiac arrhythmia following rapid imipramine withdrawal.	1989 Feb 15	2467692
Effect of thioridazine dosage on the debrisoquine hydroxylation phenotype in psychiatric patients with different CYP2D6 genotypes.	2001 Dec	11802093
Thioridazine (Mellaril) and mesoridazine (Serentil): prolongation of the QTc interval.	2001 Jan 9	11202679
Activity of phenothiazines against antibiotic-resistant Mycobacterium tuberculosis: a review supporting further studies that may elucidate the potential use of thioridazine as anti-tuberculosis therapy.	2001 May	11328759
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.	2001 Oct	11561066
Medications that prolong the QT interval.	2003 Aug 27	12941670
The relevance of prolonged QTc measurement to pediatric psychopharmacology.	2003 Jun	12921471
Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype.	2003 May	12682803
Physical health monitoring of patients with schizophrenia.	2004 Aug	15285957
Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel.	2004 Jan	14734057
Diastereotopic analysis of mesoridazine besylate (Serentil).	2004 Oct	15290689
Synthesis, receptor binding and functional studies of mesoridazine stereoisomers.	2004 Sep 6	15357957
Schizophrenia, antipsychotic drugs, and cardiovascular disease.	2005	16107178
Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist.	2005 Dec	16135699
Expert Canadian consensus suggestions on the rational, clinical use of ziprasidone in the treatment of schizophrenia and related psychotic disorders.	2005 Jun	18568067
Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia.	2006 Feb 21	16504026
Effect of thioridazine on gap junction intercellular communication in connexin 43-expressing cells.	2006 Jul	16685461
Frequency of high-risk use of QT-prolonging medications.	2006 Jun	16178046
Altering extracellular potassium concentration does not modulate drug block of human ether-a-go-go-related gene (hERG) channels.	2006 Nov	17042915
Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review.	2006 Sep	17017818
No effect of the CYP1A2*1F genotype on thioridazine, mesoridazine, sulforidazine plasma concentrations in psychiatric patients.	2007 May	17345072
Factors affecting drug concentrations and QT interval during thioridazine therapy.	2007 Nov	17460606
Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.	2007 Nov	17410120
Hospitalization risk associated with typical and atypical antipsychotic use in community-dwelling elderly patients.	2008 Oct	19028375
Using molecular similarity to highlight the challenges of routine immunoassay-based drug of abuse/toxicology screening in emergency medicine.	2009 Apr 28	19400959
Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance.	2009 Aug	20676275
Mechanisms of action of antipsychotic drugs of different classes, refractoriness to therapeutic effects of classical neuroleptics, and individual variation in sensitivity to their actions: Part II.	2009 Dec	20514211
Mechanisms of action of antipsychotic drugs of different classes, refractoriness to therapeutic effects of classical neuroleptics, and individual variation in sensitivity to their actions: Part I.	2009 Dec	20514210
Relevance of CYP2D6 -1584C>G polymorphism for thioridazine:mesoridazine plasma concentration ratio in psychiatric patients.	2009 Jul	19604081
Pediatric thioridazine poisoning as a result of a pharmacy compounding error.	2009 Jun 8	21589825
Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions.	2010 Apr 7	20396637
Identification of novel substrates for human cytochrome P450 2J2.	2010 Feb	19923256
Phenothiazine-type antipsychotics elicit cutaneous analgesia in rats.	2010 Mar	20434106
Oncologic outcomes of robotic-assisted total mesorectal excision for the treatment of rectal cancer.	2010 May	20395863
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.	2013 Jun	23529728

Patents

Sample Use Guides

In Vivo Use Guide

A starting dose of 50 mg of Serentil (Mesoridazine) three times a day is recommended. The usual optimal total daily dose range is 100-400 mg per day.

Route of Administration: Oral

In Vitro Use Guide

[3H]IP production was measured in COS-7 cells expressing human 5-HT2C-INI receptors at 2.7 pmol/mg of protein. Cells were treated with or without 1 uM Mesoridazine. Basal activity was determined by subtracting [3H]IP produced in cells transfected with vector only.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:14:31 UTC 2023` Edited by `admin` on `Fri Dec 15 16:14:31 UTC 2023`
Record UNII	T4G2I958J2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MESORIDAZINE BESYLATE

Common Name

English

NSC-760073

Code

English

MESORIDAZINE BENZENESULFONATE [MI]

Common Name

English

10H-PHENOTHIAZINE, 10-(2-(1-METHYL-2-PIPERIDINYL)ETHYL)-2-(METHYLSULFINYL)-, (±)-, MONOBENZENESULFONATE

Systematic Name

English

MESORIDAZINE BESYLATE [ORANGE BOOK]

Common Name

English

MESORIDAZINE BENZENESULFONATE

Common Name

English

MESORIDAZINE BESILATE

Common Name

English

SERENTIL

Brand Name

English

MESORIDAZINE BESYLATE [VANDF]

Common Name

English

(±)-10-(2-(1-METHYL-2-PIPERIDYL)ETHYL)-2-(METHYLSULPHINYL)PHENOTHIAZINE MONOBENZENESULPHONATE

Systematic Name

English

MESORIDAZINE BESYLATE [USP-RS]

Common Name

English

Mesoridazine besilate [WHO-DD]

Common Name

English

MESORIDAZINE BESYLATE [USP IMPURITY]

Common Name

English

MESORIDAZINE BESILATE [MART.]

Common Name

English

10H-PHENOTHIAZINE, 10-(2-(1-METHYL-2-PIPERIDINYL)ETHYL)-2-(METHYLSULPHINYL)-, (±)-, MONOBENZENESULPHONATE

Systematic Name

English

(±)-10-(2-(1-METHYL-2-PIPERIDYL)ETHYL)-2-(METHYLSULFINYL)PHENOTHIAZINE MONOBENZENESULFONATE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66883