Thioproperazine

Identification

Summary

Thioproperazine is an antipsychotic indicated for the management of acute and chronic schizophrenia, including cases that are refractory to more common neuroleptics. May also be used to treat manic syndromes.

Brand Names
Majeptil
Generic Name
Thioproperazine
DrugBank Accession Number
DB01622
Background

Thioproperazine is a potent neuroleptic with antipsychotic properties. Thioproperazine has a marked cataleptic and antiapomorphine activity associated with relatively slight sedative, hypothermic and spasmolytic effects. It is virtually without antiserotonin and hypotensive action and has no antihistaminic property. It is used for the treatment of all types of acute and chronic schizophrenia, including those which did not respond to the usual neuroleptics; manic syndromes.

Type
Small Molecule
Groups
Experimental
Structure
Thumb
Weight
Average: 446.629
Monoisotopic: 446.181017604
Chemical Formula
C22H30N4O2S2
Synonyms
  • (Thioproperazine)-2-dimethylsulfamido-(10-(3-1-methylpiperazinyl-4)propyl)-phenothiazine
  • 2-dimethylsulfamido-(10-(3-1-methylpiperazinyl-4)propyl)-phenothiazine
  • N,N-Dimethyl-10-[3-(4-methyl-1-piperazinyl)propyl]-10H-phenothiazine-2-sulfonamide
  • N,N-Dimethyl-10-[3-(4-methyl-1-piperazinyl)propyl]phenothiazine-2-sulfonamide
  • Thioperazine
  • Thioproperazin
  • Thioproperazine
  • Thioproperazinum
  • Tioproferazina
  • Tioproperazina

Pharmacology

Indication

For the treatment of all types of acute and chronic schizophrenia, including those which did not respond to the usual neuroleptics; manic syndromes.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Thioproperazine is a potent neuroleptic with antipsychotic properties. Thioproperazine has a marked cataleptic and antiapomorphine activity associated with relatively slight sedative, hypothermic and spasmolytic effects. It is virtually without antiserotonin and hypotensive action and has no antihistaminic property.

Mechanism of action

Thioproperazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects).

TargetActionsOrganism
ADopamine D2 receptor
antagonist
Humans
UDopamine D1 receptor
antagonist
Humans
AAlpha-1A adrenergic receptor
antagonist
Humans
AAlpha-1B adrenergic receptor
antagonist
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Overdosage may result in severe extrapyramidal symptoms with dysphagia, marked sialorrhea, persistent and rapidly increasing hyperthermia, pulmonary syndrome, state of shock with pallor and profuse sweating, which may be followed by collapse and coma. LD50 in mice is 70 mg/kg I.V., 120 mg/kg I.P., 500 mg/kg S.C. and 830 mg/kg P.O.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Thioproperazine is combined with 1,2-Benzodiazepine.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Thioproperazine.
AceclofenacThe risk or severity of hypertension can be increased when Thioproperazine is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Thioproperazine is combined with Acemetacin.
AcenocoumarolThe risk or severity of adverse effects can be increased when Thioproperazine is combined with Acenocoumarol.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Thioproperazine.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Thioproperazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Acetophenazine is combined with Thioproperazine.
Acetylsalicylic acidThe risk or severity of hypertension can be increased when Acetylsalicylic acid is combined with Thioproperazine.
AclidiniumThioproperazine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
Interactions
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Food Interactions
  • Avoid alcohol.
  • Take with food. Food decreases irritation.

Products

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International/Other Brands
Majeptil
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Majeptil Tab 10mgTablet10 mgOralErfa Canada 2012 Inc1962-12-31Not applicableCanada flag

Categories

ATC Codes
N05AB08 — Thioproperazine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenothiazines. These are polycyclic aromatic compounds containing a phenothiazine moiety, which is a linear tricyclic system that consists of a two benzene rings joined by a para-thiazine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiazines
Sub Class
Phenothiazines
Direct Parent
Phenothiazines
Alternative Parents
Alkyldiarylamines / Diarylthioethers / N-methylpiperazines / Organosulfonamides / Benzenoids / 1,4-thiazines / Aminosulfonyl compounds / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
1,4-diazinane / Alkyldiarylamine / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle / Benzenoid / Diarylthioether / Hydrocarbon derivative
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, sulfonamide, N-alkylpiperazine, N-methylpiperazine (CHEBI:59120)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
YJ050AQ56X
CAS number
316-81-4
InChI Key
VZYCZNZBPPHOFY-UHFFFAOYSA-N
InChI
InChI=1S/C22H30N4O2S2/c1-23(2)30(27,28)18-9-10-22-20(17-18)26(19-7-4-5-8-21(19)29-22)12-6-11-25-15-13-24(3)14-16-25/h4-5,7-10,17H,6,11-16H2,1-3H3
IUPAC Name
N,N-dimethyl-10-[3-(4-methylpiperazin-1-yl)propyl]-10H-phenothiazine-2-sulfonamide
SMILES
CN(C)S(=O)(=O)C1=CC2=C(SC3=CC=CC=C3N2CCCN2CCN(C)CC2)C=C1

References

General References
Not Available
Human Metabolome Database
HMDB0015559
KEGG Drug
D08585
PubChem Compound
9429
PubChem Substance
46507111
ChemSpider
9058
BindingDB
81793
RxNav
10498
ChEBI
59120
ChEMBL
CHEMBL609109
ZINC
ZINC000022446685
PharmGKB
PA164754875
Wikipedia
Thioproperazine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychosis / Schizoaffective Disorders / Schizophrenia / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral10 mg
Prices
Unit descriptionCostUnit
Majeptil 10 mg Tablet0.6USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)140 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.0569 mg/mLALOGPS
logP3.09ALOGPS
logP2.83ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)8.36ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area47.1 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity126.95 m3·mol-1ChemAxon
Polarizability49.62 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.996
Blood Brain Barrier+0.9629
Caco-2 permeable-0.6568
P-glycoprotein substrateSubstrate0.7908
P-glycoprotein inhibitor IInhibitor0.8563
P-glycoprotein inhibitor IIInhibitor0.7979
Renal organic cation transporterNon-inhibitor0.5396
CYP450 2C9 substrateNon-substrate0.7704
CYP450 2D6 substrateNon-substrate0.8194
CYP450 3A4 substrateSubstrate0.5366
CYP450 1A2 substrateNon-inhibitor0.8243
CYP450 2C9 inhibitorNon-inhibitor0.8758
CYP450 2D6 inhibitorInhibitor0.6293
CYP450 2C19 inhibitorNon-inhibitor0.7713
CYP450 3A4 inhibitorInhibitor0.6338
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6663
Ames testNon AMES toxic0.7056
CarcinogenicityNon-carcinogens0.8109
BiodegradationNot ready biodegradable0.9934
Rat acute toxicity2.6623 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7265
hERG inhibition (predictor II)Non-inhibitor0.5303
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (11 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-01vo-9411000000-e918c0715fd27f21a62f
GC-MS Spectrum - EI-BGC-MSsplash10-0229-6924100000-fcb76747a5faaee6b722
GC-MS Spectrum - CI-BGC-MSsplash10-0002-1001900000-0b26a1120865f1ac9f3a
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Drugtargets2
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insights and accelerate drug research.
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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Oades RD, Rao ML, Bender S, Sartory G, Muller BW: Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. Behav Pharmacol. 2000 Jun;11(3-4):317-30. [Article]
  2. Seeman P: Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002 Feb;47(1):27-38. [Article]
  3. Wu S, Xing Q, Gao R, Li X, Gu N, Feng G, He L: Response to chlorpromazine treatment may be associated with polymorphisms of the DRD2 gene in Chinese schizophrenic patients. Neurosci Lett. 2005 Mar 7;376(1):1-4. Epub 2004 Dec 2. [Article]
  4. Wu SN, Gao R, Xing QH, Li HF, Shen YF, Gu NF, Feng GY, He L: Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients. Acta Pharmacol Sin. 2006 Aug;27(8):966-70. [Article]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  6. Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. doi: 10.3371/CSRP.4.1.5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. Kanba S, Suzuki E, Nomura S, Nakaki T, Yagi G, Asai M, Richelson E: Affinity of neuroleptics for D1 receptor of human brain striatum. J Psychiatry Neurosci. 1994 Jul;19(4):265-9. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Cahir M, King DJ: Antipsychotics lack alpha 1A/B adrenoceptor subtype selectivity in the rat. Eur Neuropsychopharmacol. 2005 Mar;15(2):231-4. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Kitamura K, Omran AA, Nagata C, Kamijima Y, Tanaka R, Takegami S, Kitade T: Effects of inorganic ions on the binding of triflupromazine and chlorpromazine to bovine serum albumin studied by spectrometric methods. Chem Pharm Bull (Tokyo). 2006 Jul;54(7):972-6. [Article]
  2. Rukhadze MD, Bezarashvili GS, Sidamonidze NS, Tsagareli SK: Investigation of binding process of chlorpromazine to bovine serum albumin by means of passive and active experiments. Biomed Chromatogr. 2001 Oct;15(6):365-73. [Article]
  3. Silva D, Cortez CM, Louro SR: Quenching of the intrinsic fluorescence of bovine serum albumin by chlorpromazine and hemin. Braz J Med Biol Res. 2004 Jul;37(7):963-8. Epub 2004 Jun 22. [Article]

Drug created on August 29, 2007 20:17 / Updated on September 19, 2021 19:53