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Details

Stereochemistry RACEMIC
Molecular Formula C21H26N2S2.ClH
Molecular Weight 407.035
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of THIORIDAZINE HYDROCHLORIDE

SMILES

Cl.CSC1=CC=C2SC3=CC=CC=C3N(CCC4CCCCN4C)C2=C1

InChI

InChIKey=NZFNXWQNBYZDAQ-UHFFFAOYSA-N
InChI=1S/C21H26N2S2.ClH/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;1H

HIDE SMILES / InChI

Molecular Formula C21H26N2S2
Molecular Weight 370.575
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Thioridazine (Mellaril or Melleril) is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. Thioridazine blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain; blocks alpha-adrenergic effect depresses the release of hypothalamic and hypophyseal hormones and is believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis. Thioridazine primary use in medicine was the treatment of schizophrenia. Thioridazine was also tried with some success as a treatment for various psychiatric symptoms seen in people with dementia, but chronic use of thioridazine and other antipsychotics in people with dementia is not recommended. Thioridazine prolongs the QTc interval in a dose-dependent manner. It produces significantly less extrapyramidal side effects than most first-generation antipsychotics. Its use, along with the use of other typical antipsychotics, has been associated with degenerative retinopathies. It has a higher propensity for causing anticholinergic side effects coupled with a lower propensity for causing extrapyramidal side effects and sedation than chlorpromazine but also has a higher incidence of hypotension and cardiotoxicity. It is also known to possess a relatively high liability for causing orthostatic hypotension compared to other antipsychotics. Similarly to other first-generation antipsychotics, it has a relatively high liability for causing prolactin elevation. It is the moderate risk of causing weight gain.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
27.0 nM [Ki]
17.3 nM [IC50]
6.06 null [pIC50]
6.32 null [pIC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
MELLARIL-S

Approved Use

Thioridazine hydrochloride tablets are indicated for the management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs. Due to the risk of significant, potentially life threatening, proarrhythmic effects with thioridazine treatment, thioridazine hydrochloride tablets should be used only in patients who have failed to respond adequately to treatment with appropriate courses of other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose due to intolerable adverse effects from those drugs. Consequently, before initiating treatment with thioridazine hydrochloride tablets, it is strongly recommended that a patient be given at least two trials, each with a different antipsychotic drug product, at an adequate dose, and for an adequate duration (see WARNINGS and CONTRAINDICATIONS). However, the prescriber should be aware that thioridazine hydrochloride tablets have not been systematically evaluated in controlled trials in treatment refractory schizophrenic patients and its efficacy in such patients is unknown.

Launch Date

1978
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
131 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
THIORIDAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
117 nM
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
THIORIDAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1338 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
THIORIDAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
709 nM × h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
THIORIDAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.2 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
THIORIDAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.7 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
THIORIDAZINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
THIORIDAZINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Disc. AE: Torsade de pointes...
AEs leading to
discontinuation/dose reduction:
Torsade de pointes (1 patient)
Sources:
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Disc. AE: Hyperthermia malignant...
AEs leading to
discontinuation/dose reduction:
Hyperthermia malignant (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Torsade de pointes 1 patient
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Hyperthermia malignant 1 patient
Disc. AE
400 mg 1 times / day multiple, oral
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victimTox targets
PubMed

PubMed

TitleDatePubMed
Recurrent major ventricular arrhythmias associated with thioridazine therapy.
1971 Nov
Thioridazine incontinence.
1972 Jan 10
Thioridazine toxicity. Agranulocytosis and hepatitis with encephalopathy.
1973 Apr 23
Ventricular arrhythmias associated with use of thioridazine hydrochloride in alcohol withdrawal.
1973 Nov 24
Neuroleptic-induced tardiave dyskinesias in nonpsychotic patients.
1974 Apr
Seven cases of somnambulism induced by drugs.
1979 Jul
Susceptibility to drug-induced hypotension in post-partum psychosis.
1986 Jan
Neuroleptic-induced tics in two hyperactive children.
1986 Sep
[Ventricular arrhythmia following thioridazine poisoning].
1991 Apr
Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors.
2000 Oct
Thioridazine (Mellaril) and mesoridazine (Serentil): prolongation of the QTc interval.
2001 Jan 9
[Primary Sjögren's syndrome presenting with choreo-athetosis].
2002 Oct
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.
2003 Dec 15
Re: Thioridazine: re-evaluating the risk/benefit equation.
2003 Jun
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.
2004 Apr 15
Physical health monitoring of patients with schizophrenia.
2004 Aug
Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.
2004 Oct
Invited review: fluphenazine augments retinal oxidative stress.
2005 Aug
A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system.
2005 Feb
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.
2005 May
Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: potential sources of metabolic drug interactions.
2010 Apr 11
QT alterations in psychopharmacology: proven candidates and suspects.
2010 Jan
Effects of K openers on the QT prolongation induced by HERG-blocking drugs in guinea-pigs.
2010 Jul
A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3'-kinase (PI3K)/AKT pathway in ovarian cancer cells.
2011 Jan
Patents

Patents

Sample Use Guides

The usual starting dose for adult schizophrenic patients is 50 mg to 100 mg three times a day, with a gradual increment to a maximum of 800 mg daily if necessary. Once effective control of symptoms has been achieved, the dosage may be reduced gradually to determine the minimum maintenance dose. The total daily dosage ranges from 200 mg to 800 mg, divided into two to four doses. For pediatric patients with schizophrenia who are unresponsive to other agents, the recommended initial dose is 0.5 mg/kg/day given in divided doses. Dosage may be increased gradually until optimum therapeutic effect is obtained or the maximum dose of 3 mg/kg/day has been reached.
Route of Administration: Oral
In Vitro Use Guide
Slices of female Wistar rats frontal cortex were prepared by 350 x 350-/.tm crosschopping. These were preincubated for 1 h in Krebsbicarbonate buffer at 37°C in the presence of O2/CO2 (95:5). Aliquots of gravity-packed slices (50 mkl) were dispensed into 13 x 100 glass tubes containing 250 mk1 of 5 mkCi [3H]myo-inositol (Amersham, Les Ulis, France; specific activity 80-120 Ci/mmol) and, after 20 min incubation, antagonist (Thioridazine) or buffer, each containing pargyline and lithium chloride (final concentrations 10 mkM and 10 mM) were added and incubation continued for 10 min. Serotonin (0.6 mkM final) or buffer was added for a stimulation period of 60 min. The reaction was stopped by three volumes of chloroform/methanol (1:2). Extraction and separation of phosphoinositol was by anion-exchange chromatography
Substance Class Chemical
Created
by admin
on Mon Mar 31 19:10:27 GMT 2025
Edited
by admin
on Mon Mar 31 19:10:27 GMT 2025
Record UNII
4WCI67NK8M
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
THIORIDAZINE HYDROCHLORIDE
EP   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
NSC-186060
Preferred Name English
THIORIDAZINE HYDROCHLORIDE [USP-RS]
Common Name English
THIORIDAZINE HYDROCHLORIDE [MART.]
Common Name English
THIORIDAZINE HYDROCHLORIDE [JAN]
Common Name English
THIORIDAZINE HYDROCHLORIDE [VANDF]
Common Name English
Thioridazine hydrochloride [WHO-DD]
Common Name English
10H-PHENOTHIAZINE, 10-(2-(1-METHYL-2-PIPERIDINYL)ETHYL)-2-(METHYLTHIO)-, MONOHYDROCHLORIDE
Common Name English
THIORIDAZINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
THIORIDAZINE HCL
Common Name English
THIORIDAZINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
THIORIDAZINE HYDROCHLORIDE [MI]
Common Name English
THIORIDAZINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
10-[2-(1-Methyl-2-piperidyl)ethyl]-2-(methylthio)phenothiazine monohydrochloride
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C29710
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
Code System Code Type Description
RS_ITEM_NUM
1663008
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
ChEMBL
CHEMBL479
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
PUBCHEM
66062
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
CAS
130-61-0
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
SMS_ID
100000092341
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
EVMPD
SUB04821MIG
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
NCI_THESAURUS
C29498
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
NSC
186060
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
EPA CompTox
DTXSID9049401
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
ECHA (EC/EINECS)
204-992-8
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
DAILYMED
4WCI67NK8M
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
CHEBI
48566
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
RXCUI
203165
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY RxNorm
DRUG BANK
DBSALT000503
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
MERCK INDEX
m10782
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY Merck Index
FDA UNII
4WCI67NK8M
Created by admin on Mon Mar 31 19:10:27 GMT 2025 , Edited by admin on Mon Mar 31 19:10:27 GMT 2025
PRIMARY
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BASIS OF STRENGTH->SUBSTANCE
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BASIS OF STRENGTH->SUBSTANCE
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ACTIVE MOIETY