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Details

Stereochemistry RACEMIC
Molecular Formula C21H26N2S2
Molecular Weight 370.5775
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of THIORIDAZINE

SMILES

CN1CCCCC1CCN2c3ccccc3Sc4ccc(cc42)SC

InChI

InChIKey=KLBQZWRITKRQQV-UHFFFAOYSA-N
InChI=1S/C21H26N2S2/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

HIDE SMILES / InChI

Molecular Formula C21H26N2S2
Molecular Weight 370.5775
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

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

2.77516812E11
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
Co-administed with::
lithium
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
Co-administed with::
lithium
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
The bucco-linguo-masticatory syndrome as a side-effect of neuroleptics therapy.
1967
Recurrent major ventricular arrhythmias associated with thioridazine therapy.
1971 Nov
Thioridazine in schizophrenia.
1971 Sep 20
Thioridazine incontinence.
1972 Jan 10
Hypertensive episodes after adding methylphenidate (Ritalin) to tricyclic antidepressants. (Report of three cases and review of clinical advantages).
1972 Jul-Aug
Thioridazine toxicity. Agranulocytosis and hepatitis with encephalopathy.
1973 Apr 23
The therapeutic use of diazepam for akathisia.
1973 Jul-Aug
Ventricular arrhythmias associated with use of thioridazine hydrochloride in alcohol withdrawal.
1973 Nov 24
Neuroleptic-induced tardiave dyskinesias in nonpsychotic patients.
1974 Apr
Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.
1976 Feb
Seven cases of somnambulism induced by drugs.
1979 Jul
Effect of bromocriptine mesylate on induced hyperprolactinemia in stabilized psychiatric outpatients undergoing neuroleptic treatment.
1985
Thioridazine toxicity--an experimental cardiovascular study of thioridazine and its major metabolites in overdose.
1985 Apr
Cardiorespiratory depression and haemolysis due to thioridazine overdose in the rat.
1985 Jul
Drug-induced torsade de pointes.
1985 Nov-Dec
The effect of thioridazine on prolactinoma growth in a schizophrenic man: case report.
1985 Oct
Tics with combined thioridazine-methylphenidate therapy: case report.
1986 Jan
Tourette-like syndrome following low dose short-term neuroleptic treatment.
1986 May
Neuroleptic-induced tics in two hyperactive children.
1986 Sep
Meige's syndrome associated with neuroleptic treatment.
1988 Apr
Attempted strangulation during phenothiazine-induced sleep-walking and night terrors.
1988 Nov
A case of secondary mania.
1988 Winter
Drug-induced tremor of the tongue.
1989 Feb
Renal and hepatic impairment in association with diclofenac administration.
1989 Jul
Myxedema coma associated with lithium therapy.
1989 Sep
Seizure promotion and protection by D-1 and D-2 dopaminergic drugs in the mouse.
1990 Aug
Neurologic approach to drug-induced movement disorders: a study of 125 patients.
1990 May
[Ventricular arrhythmia following thioridazine poisoning].
1991 Apr
Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1.
1991 Apr 18
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
Spasmodic dysphonia, a rare form of tardive dystonia, induced by low-dose risperidone?
2004 Mar
Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.
2004 Oct
[Sonapax use in the clinical practice].
2005 Apr
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
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations].
2006 Jun
Frequency of high-risk use of QT-prolonging medications.
2006 Jun
In vitro detection of drug-induced phospholipidosis using gene expression and fluorescent phospholipid based methodologies.
2007 Sep
Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: potential sources of metabolic drug interactions.
2010 Apr 11
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.
2010 Dec
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
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Comparison of a genomic and a multiplex cell imaging approach for the detection of phospholipidosis.
2011 Oct
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.
2013 Dec
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.
2013 Jun
HepG2 cells simultaneously expressing five P450 enzymes for the screening of hepatotoxicity: identification of bioactivable drugs and the potential mechanism of toxicity involved.
2013 Jun
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 Fri Jun 25 20:55:14 UTC 2021
Edited
by admin
on Fri Jun 25 20:55:14 UTC 2021
Record UNII
N3D6TG58NI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
THIORIDAZINE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
NOVORIDAZINE
Brand Name English
MELLARIL-S
Brand Name English
THIORIDAZINE [MART.]
Common Name English
THIORIDAZINE [USAN]
Common Name English
THIORIL
Brand Name English
MELLERETTE
Common Name English
(+/-)-THIORIDAZINE
Common Name English
DL-THIORIDAZINE
Common Name English
TP-21
Code English
THIORIDAZINE PROLONGATUM
Common Name English
THIORIDAZINE [INN]
Common Name English
THIORIDAZINE [VANDF]
Common Name English
THIORIDAZINE [EP MONOGRAPH]
Common Name English
THIORIDAZINE [HSDB]
Common Name English
THIORIDAZINE [WHO-DD]
Common Name English
THIORIDAZINE [USP MONOGRAPH]
Common Name English
THIORIDAZINE [MI]
Common Name English
SONAPAX
Common Name English
MELLARIL
Brand Name English
10-(2-(1-METHYL-2-PIPERIDYL)ETHYL)-2-(METHYLTHIO)PHENOTHIAZINE
Systematic Name English
THIORIDAZINE [USP-RS]
Common Name English
THIORIDAZINE [ORANGE BOOK]
Common Name English
10H-PHENOTHIAZINE, 10-(2-(1-METHYL-2-PIPERIDINYL)ETHYL)-2-(METHYLTHIO)-
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000007544
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
NDF-RT N0000007544
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
NDF-RT N0000007544
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
NDF-RT N0000175746
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
WHO-VATC QN05AC02
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WHO-ATC N05AC02
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
NCI_THESAURUS C29710
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
LIVERTOX 954
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
Code System Code Type Description
PUBCHEM
5452
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-044-2
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
INN
818
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PRIMARY
ChEMBL
CHEMBL479
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PRIMARY
DRUG BANK
DB00679
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PRIMARY
FDA UNII
N3D6TG58NI
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
CAS
50-52-2
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
WIKIPEDIA
THIORIDAZINE
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
HSDB
3189
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
IUPHAR
100
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PRIMARY
RXCUI
10502
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY RxNorm
USP_CATALOG
1662504
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PRIMARY USP-RS
MESH
D013881
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PRIMARY
EPA CompTox
50-52-2
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PRIMARY
NCI_THESAURUS
C61971
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PRIMARY
LACTMED
Thioridazine
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
DRUG CENTRAL
2637
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PRIMARY
EVMPD
SUB10984MIG
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY
MERCK INDEX
M10782
Created by admin on Fri Jun 25 20:55:14 UTC 2021 , Edited by admin on Fri Jun 25 20:55:14 UTC 2021
PRIMARY Merck Index
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
EP
METABOLIC ENZYME -> INHIBITOR
IC50
BINDER->LIGAND
SALT/SOLVATE -> PARENT
BASIS OF STRENGTH->SUBSTANCE
ASSAY (TITRATION)
USP
Related Record Type Details
METABOLITE ACTIVE -> PARENT
METABOLITE -> PARENT
METABOLITE ACTIVE -> PARENT
Metabolite to parent drug ratio in non-uraemic human plasma. Mesoridazine is twice as potent as the parent drug in man and has been introduced into clinical use as an antipsychotic.
METABOLITE TO PARENT DRUG RATIO
PLASMA; URINE
METABOLITE INACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
Amount excreted in 24 hour period. Percent of dose excreted in urine as metabolite.
AMOUNT EXCRETED
URINE
METABOLITE ACTIVE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 1.5
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 2.4
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 0.5
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 1.9
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY