THIORIDAZINE HYDROCHLORIDE

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 Search

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

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
Recurrent major ventricular arrhythmias associated with thioridazine therapy.	1971 Nov	5113695
Thioridazine incontinence.	1972 Jan 10	5066616
Thioridazine toxicity. Agranulocytosis and hepatitis with encephalopathy.	1973 Apr 23	4739612
Ventricular arrhythmias associated with use of thioridazine hydrochloride in alcohol withdrawal.	1973 Nov 24	4758451
Neuroleptic-induced tardiave dyskinesias in nonpsychotic patients.	1974 Apr	4816841
Seven cases of somnambulism induced by drugs.	1979 Jul	453369
Susceptibility to drug-induced hypotension in post-partum psychosis.	1986 Jan	3559152
Neuroleptic-induced tics in two hyperactive children.	1986 Sep	2875666
[Ventricular arrhythmia following thioridazine poisoning].	1991 Apr	2053762
Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors.	2000 Oct	10991983
Thioridazine (Mellaril) and mesoridazine (Serentil): prolongation of the QTc interval.	2001 Jan 9	11202679
[Primary Sjögren's syndrome presenting with choreo-athetosis].	2002 Oct	12739384
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia.	2003 Dec 15	14678746
Re: Thioridazine: re-evaluating the risk/benefit equation.	2003 Jun	12938870
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors.	2004 Apr 15	15135088
Physical health monitoring of patients with schizophrenia.	2004 Aug	15285957
Automated tight seal electrophysiology for assessing the potential hERG liability of pharmaceutical compounds.	2004 Oct	15671647
Invited review: fluphenazine augments retinal oxidative stress.	2005 Aug	16117689
A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system.	2005 Feb	15342952
Stable expression of constitutively activated mutant h5HT6 and h5HT7 serotonin receptors: inverse agonist activity of antipsychotic drugs.	2005 May	15821958
Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: potential sources of metabolic drug interactions.	2010 Apr 11	20097249
QT alterations in psychopharmacology: proven candidates and suspects.	2010 Jan	20210726
Effects of K openers on the QT prolongation induced by HERG-blocking drugs in guinea-pigs.	2010 Jul	20636881
A gene signature-based approach identifies thioridazine as an inhibitor of phosphatidylinositol-3'-kinase (PI3K)/AKT pathway in ovarian cancer cells.	2011 Jan	21035837

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 `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

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Name

Type

Language

THIORIDAZINE HYDROCHLORIDE

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