THIORIDAZINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C21H26N2S2
Molecular Weight	370.575
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

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	370.575
Charge	0
Count

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

Description
Sources: https://www.drugs.com/pro/thioridazine.html

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.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12747773	Antagonist 2849	27.0 nM [Ki]
Dopamine D1 receptor 106 Target ID: CHEMBL265 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2888897	Antagonist 2849	17.3 nM [IC50]
Serotonin 2c (5-HT2c) receptor 131 Target ID: CHEMBL225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7898773	Antagonist 2849	6.06 null [pIC50]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7898773	Antagonist 2849	6.32 null [pIC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 305 Sources: https://www.drugs.com/pro/thioridazine.html	Primary		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
131 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10952475	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2007317	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

Value	Dose	Co-administered	Analyte	Population
1338 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10952475	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2007317	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
12.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10952475	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2007317	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.rxmed.com/b.main/b2.pharmaceutical/b2.1.monographs/cps-_monographs/CPS-_(General_Monographs-_M)/MELLARIL.html			THIORIDAZINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/6145728	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/6145728	Disc. AE: Torsade de pointes... AEs leading to discontinuation/dose reduction: Torsade de pointes (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/6145728
400 mg 1 times / day multiple, oral Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/646545	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/646545	Disc. AE: Hyperthermia malignant... AEs leading to discontinuation/dose reduction: Hyperthermia malignant (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/646545

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/6145728	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/6145728
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: https://pubmed.ncbi.nlm.nih.gov/646545	unhealthy Health Status: unhealthy Sources: https://pubmed.ncbi.nlm.nih.gov/646545

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	inhibitor 2438	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741 BCRP 910 MRP2 499 Nav1.5 116	CYP2C19 1119 CYP1A2 1197

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/16382211/ Page: 4.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://dmd.aspetjournals.org/content/27/9/1078.full Page: abstract	yes [IC50 2.7 uM]
BCRP 985	inhibitor 4027 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: 3.0	yes
MRP2 625	inhibitor 4027 Sources: https://link.springer.com/article/10.1007/s11095-009-9896-0 Page: 3.0	yes
P-gp 1932	inhibitor 4027 Sources: https://link.springer.com/article/10.1007/s13277-014-2278-1 Page: abstract	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250500158134 Page: 10.0	weak
CYP2C19 1119	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250500158134 Page: 10.0	weak
CYP2D6 1388	substrate 4014 Sources: https://www.tandfonline.com/doi/abs/10.1080/00498250500158134 Page: 10.0	yes
CYP3A4 1946	substrate 4014 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.2007.03021.x Page: 3.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 119	inhibitor 2237 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5603905/pdf/nihms905997.pdf Page: 4.0
hERG 2263	inhibitor 2237 Sources: https://physoc.onlinelibrary.wiley.com/doi/pdfdirect/10.14814/phy2.14385 Page: 4.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:48566	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:48566
ChemicalBook	CB4256836	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4256836
eMolecules	595203	https://www.emolecules.com/cgi-bin/more?vid=595203
MolPort	MolPort-001-727-928	https://www.molport.com/shop/molecule-link/MolPort-001-727-928

PubMed

Title	Date	PubMed
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.	2013-12	24052561
Phenothiazines inhibit hepatitis C virus entry, likely by increasing the fluidity of cholesterol-rich membranes.	2013-06	23529728
HepG2 cells simultaneously expressing five P450 enzymes for the screening of hepatotoxicity: identification of bioactivable drugs and the potential mechanism of toxicity involved.	2013-06	23397584
Antitubercular pharmacodynamics of phenothiazines.	2013-04	23228936
A repurposing approach identifies off-patent drugs with fungicidal cryptococcal activity, a common structural chemotype, and pharmacological properties relevant to the treatment of cryptococcosis.	2013-02	23243064
Comparison of a genomic and a multiplex cell imaging approach for the detection of phospholipidosis.	2011-10	21515356
Estimating the risk of drug-induced proarrhythmia using human induced pluripotent stem cell-derived cardiomyocytes.	2011-09	21693436
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011-07-14	21599003
A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3'-kinase (PI3K)/AKT pathway in ovarian cancer cells.	2011-01	21035837
Identification of human Ether-à-go-go related gene modulators by three screening platforms in an academic drug-discovery setting.	2010-12	21158687
Effects of K openers on the QT prolongation induced by HERG-blocking drugs in guinea-pigs.	2010-07	20636881
Persistent dystonia associated with buspirone.	1990-12	2247245
Spectral electroretinography in thioridazine toxicity.	1990-08	2221706
Ventricular tachycardia associated with desipramine and thioridazine.	1990	2300645
Myxedema coma associated with lithium therapy.	1989-09	2773973
Renal and hepatic impairment in association with diclofenac administration.	1989-07	2602249
Prolonged fever without extrapyramidal symptoms during neuroleptic treatment.	1989-06	2738187
Drug-induced tremor of the tongue.	1989-02	2925349
Attempted strangulation during phenothiazine-induced sleep-walking and night terrors.	1988-11	3255460
Hyperthermia, hypertension, hypertonia, and coma in a massive thioridazine overdose.	1988-07	3390252
Meige's syndrome associated with neuroleptic treatment.	1988-04	2894781
[Mechanism of the development of thioridazine retinopathy].	1988-01	3337876
A case of secondary mania.	1988	3340705
Rapid death resulting from mesoridazine overdose.	1987-02	3824877
Iatrogenic torsade de pointes induced by thioridazine.	1987-01	3790644
Baclofen-induced catatonia.	1986-12	3805341
Neuroleptic-induced tics in two hyperactive children.	1986-09	2875666
Limited effect of magnesium sulphate on torsades de pointes ventricular tachycardia.	1986-08	3744606
Drug-induced dystonia in neuronal ceroid-lipofuscinosis.	1986-07-01	3508694
Neurotoxicity induced by combined lithium-thioridazine treatment.	1986-07	3089336
Haloperidol versus thioridazine in the treatment of behavioral symptoms in senile dementia of the Alzheimer's type: preliminary findings.	1986-06	3711028
Tourette-like syndrome following low dose short-term neuroleptic treatment.	1986-05	3459568
Tics with combined thioridazine-methylphenidate therapy: case report.	1986-01	3941061
Susceptibility to drug-induced hypotension in post-partum psychosis.	1986-01	3559152
Drug-induced torsade de pointes.	1985-11-01	2416504
The effect of thioridazine on prolactinoma growth in a schizophrenic man: case report.	1985-10	4065553
Molindone hydrochloride treatment of hospitalized children with conduct disorder.	1985-08	3894338
Cardiorespiratory depression and haemolysis due to thioridazine overdose in the rat.	1985-07	2863351
Thioridazine toxicity--an experimental cardiovascular study of thioridazine and its major metabolites in overdose.	1985-04	3992882
Effect of bromocriptine mesylate on induced hyperprolactinemia in stabilized psychiatric outpatients undergoing neuroleptic treatment.	1985	4047382
Seven cases of somnambulism induced by drugs.	1979-07	453369
Neuroleptic-induced tardiave dyskinesias in nonpsychotic patients.	1974-04	4816841
Ventricular arrhythmias associated with use of thioridazine hydrochloride in alcohol withdrawal.	1973-11-24	4758451
The therapeutic use of diazepam for akathisia.	1973-07-01	4795129
Thioridazine toxicity. Agranulocytosis and hepatitis with encephalopathy.	1973-04-23	4739612
Hypertensive episodes after adding methylphenidate (Ritalin) to tricyclic antidepressants. (Report of three cases and review of clinical advantages).	1972-07-01	4671919
Thioridazine incontinence.	1972-01-10	5066616
Recurrent major ventricular arrhythmias associated with thioridazine therapy.	1971-11	5113695
Thioridazine in schizophrenia.	1971-09-20	5109828
The bucco-linguo-masticatory syndrome as a side-effect of neuroleptics therapy.	1967	4383787

Patents

Sample Use Guides

In Vivo Use Guide

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 `Wed Apr 02 07:53:51 GMT 2025` Edited by `admin` on `Wed Apr 02 07:53:51 GMT 2025`
Record UNII	N3D6TG58NI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MELLARIL-S

Preferred Name

English

THIORIDAZINE

Official Name

English

Thioridazine [WHO-DD]

Common Name

English

NOVORIDAZINE

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 [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