U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry MIXED
Molecular Formula C21H26N2OS2
Molecular Weight 386.5769
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MESORIDAZINE

SMILES

CN1CCCCC1CCN2c3ccccc3Sc4ccc(cc42)S(=O)C

InChI

InChIKey=SLVMESMUVMCQIY-UHFFFAOYSA-N
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

HIDE SMILES / InChI

Molecular Formula C21H26N2OS2
Molecular Weight 386.5769
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P14416
Gene ID: 1813.0
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
3.0 nM [Ki]
Target ID: P28223
Gene ID: 3356.0
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Primary
SERENTIL

Approved Use

Psychosis

Launch Date

4.9248E9
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
240 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
2400 ng × h/mL
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.5 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
75%
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

Doses

DosePopulationAdverse events​
3.1 g single, oral
Overdose
Dose: 3.1 g
Route: oral
Route: single
Dose: 3.1 g
Sources:
healthy, 20 years
n = 1
Health Status: healthy
Condition: suicide attempt
Age Group: 20 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Ventricular arrhythmias and cardiac arrest...
AEs leading to
discontinuation/dose reduction:
Ventricular arrhythmias and cardiac arrest (grade 4, 1 patient)
Sources:
16 ug/mL single, oral
Overdose
Dose: 16 ug/mL
Route: oral
Route: single
Dose: 16 ug/mL
Sources:
unhealthy, 23 years
n = 1
Health Status: unhealthy
Condition: mentally retarded
Age Group: 23 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5, 1 patient)
Sources:
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:
healthy, 48-62 years
n = 7
Health Status: healthy
Age Group: 48-62 years
Sex: unknown
Population Size: 7
Sources:
AEs

AEs

AESignificanceDosePopulation
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:
healthy, 20 years
n = 1
Health Status: healthy
Condition: suicide attempt
Age Group: 20 years
Sex: F
Population Size: 1
Sources:
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:
unhealthy, 23 years
n = 1
Health Status: unhealthy
Condition: mentally retarded
Age Group: 23 years
Sex: F
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Neuroleptics and neurologic reactions.
1973 Mar
Drug-induced dystonia.
1975 May
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.
1978 Oct 7
Effect of thioridazine dosage on the debrisoquine hydroxylation phenotype in psychiatric patients with different CYP2D6 genotypes.
2001 Dec
Thioridazine (Mellaril) and mesoridazine (Serentil): prolongation of the QTc interval.
2001 Jan 9
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
Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor.
2001 Oct
Medications that prolong the QT interval.
2003 Aug 27
The relevance of prolonged QTc measurement to pediatric psychopharmacology.
2003 Jun
Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype.
2003 May
Physical health monitoring of patients with schizophrenia.
2004 Aug
Mesoridazine: an open-channel blocker of human ether-a-go-go-related gene K+ channel.
2004 Jan
Diastereotopic analysis of mesoridazine besylate (Serentil).
2004 Oct
Synthesis, receptor binding and functional studies of mesoridazine stereoisomers.
2004 Sep 6
Schizophrenia, antipsychotic drugs, and cardiovascular disease.
2005
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
Time to discontinuation of atypical versus typical antipsychotics in the naturalistic treatment of schizophrenia.
2006 Feb 21
Effect of thioridazine on gap junction intercellular communication in connexin 43-expressing cells.
2006 Jul
Frequency of high-risk use of QT-prolonging medications.
2006 Jun
Altering extracellular potassium concentration does not modulate drug block of human ether-a-go-go-related gene (hERG) channels.
2006 Nov
Efficacy of typical and atypical antipsychotics for primary and comorbid anxiety symptoms or disorders: a review.
2006 Sep
No effect of the CYP1A2*1F genotype on thioridazine, mesoridazine, sulforidazine plasma concentrations in psychiatric patients.
2007 May
Factors affecting drug concentrations and QT interval during thioridazine therapy.
2007 Nov
Comparison of the effects of thioridazine and mesoridazine on the QT interval in healthy adults after single oral doses.
2007 Nov
Using molecular similarity to highlight the challenges of routine immunoassay-based drug of abuse/toxicology screening in emergency medicine.
2009 Apr 28
Iatrogenic QT Abnormalities and Fatal Arrhythmias: Mechanisms and Clinical Significance.
2009 Aug
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
Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions.
2010 Apr 7
Oncologic outcomes of robotic-assisted total mesorectal excision for the treatment of rectal cancer.
2010 May
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.
2013 Jun
Patents

Sample Use Guides

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
[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 Sat Jun 26 03:18:46 UTC 2021
Edited
by admin
on Sat Jun 26 03:18:46 UTC 2021
Record UNII
5XE4NWM740
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MESORIDAZINE
HSDB   INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
MESORIDAZINE [INN]
Common Name English
THIORIDAZINE-2-SULFOXIDE
Common Name English
THIORIDAZINE SPECIFIED IMPURITY B [EP]
Common Name English
MESORIDAZINE [MI]
Common Name English
MESORIDAZINE [VANDF]
Common Name English
NC-123
Code English
NSC-186066
Code English
LIDANAR
Brand Name English
TPS-23
Code English
10H-PHENOTHIAZINE, 10-(2-(1-METHYL-2-PIPERIDINYL)ETHYL)-2-(METHYLSULFINYL)-
Systematic Name English
MESORIDAZINE [HSDB]
Common Name English
10-(2(1-METHYL-2-PIPERIDYL)ETHYL)-2-(METHYLSULFINYL)-PHENOTHIAZINE
Systematic Name English
MESORIDAZINE [WHO-DD]
Common Name English
MESORIDAZINE [USAN]
Common Name English
THIORIDAZINE HYDROCHLORIDE SPECIFIED IMPURITY B [EP]
Common Name English
MESORIDAZINE [MART.]
Common Name English
Classification Tree Code System Code
NDF-RT N0000007544
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
WHO-VATC QN05AC03
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
NDF-RT N0000007544
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
NCI_THESAURUS C29710
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
NDF-RT N0000007544
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
NDF-RT N0000175746
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
NCI_THESAURUS C66883
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
WHO-ATC N05AC03
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
Code System Code Type Description
PUBCHEM
4078
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
ChEMBL
CHEMBL1088
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
IUPHAR
7227
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
FDA UNII
5XE4NWM740
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
WIKIPEDIA
MESORIDAZINE
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
LACTMED
Mesoridazine
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
DRUG CENTRAL
1712
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
INN
2019
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
MERCK INDEX
M7250
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY Merck Index
CAS
5588-33-0
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
HSDB
3357
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
EVMPD
SUB08786MIG
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
DRUG BANK
DB00933
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
EPA CompTox
5588-33-0
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
NCI_THESAURUS
C66100
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
MESH
D008653
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY
RXCUI
6779
Created by admin on Sat Jun 26 03:18:46 UTC 2021 , Edited by admin on Sat Jun 26 03:18:46 UTC 2021
PRIMARY RxNorm
Related Record Type Details
TARGET -> INHIBITOR
BINDER->LIGAND
Related Record Type Details
PARENT -> METABOLITE ACTIVE
Related Record Type Details
PARENT -> IMPURITY
For the calculation of contents, multiply the peak areas by 2.4
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
PARENT -> IMPURITY
For the calculation of contents, multiply the peak areas by 2.4
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY