Mesoridazine

Identification

Summary

Mesoridazine is a phenothiazine antipsychotic used to treat schizophrenia, organic brain disorders, alcoholism, and psychoneuroses.

Generic Name
Mesoridazine
DrugBank Accession Number
DB00933
Background

A phenothiazine antipsychotic with effects similar to chlorpromazine.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 386.574
Monoisotopic: 386.148654844
Chemical Formula
C21H26N2OS2
Synonyms
  • 10-(2-(1-Methyl-2-piperidyl)ethyl)-2-methylsulfinyl phenothiazine
  • 10-(2(1-Methyl-2-piperidyl)ethyl)-2-(methylsulfinyl)phenothiazine
  • 2-Methanesulfinyl-10-[2-(1-methyl-piperidin-2-yl)-ethyl]-10H-phenothiazine
  • Mesoridazina
  • Mesoridazine
  • Mesoridazinum
  • Thioridazine 2-sulfoxide
  • Thioridazine thiomethyl sulfoxide
  • Thioridazine-2-sulfoxide
External IDs
  • NC-123
  • TPS-23

Pharmacology

Indication

Used in the treatment of schizophrenia, organic brain disorders, alcoholism and psychoneuroses.

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Mesoridazine, the besylate salt of a metabolite of thioridazine, is a phenothiazine tranquilizer. Pharmacological studies in laboratory animals have established that mesoridazine has a spectrum of pharmacodynamic actions typical of a major tranquilizer. In common with other tranquilizers it inhibits spontaneous motor activity in mice, prolongs thiopental and hexobarbital sleeping time in mice and produces spindles and block of arousal reaction in the EEG of rabbits. It is effective in blocking spinal reflexes in the cut and antagonizes d-amphetamine excitation and toxicity in grouped mice. It shows a moderate adrenergic blocking activity in vitro and in vivo and antagonizes 5-hydroxytryptamine in vivo. Intravenously administered, it lowers the blood pressure of anesthetized dogs. It has a weak antiacetylcholine effect in vitro.

Mechanism of action

Based upon animal studies, mesoridazine, as with other phenothiazines, acts indirectly on reticular formation, whereby neuronal activity into reticular formation is reduced without affecting its intrinsic ability to activate the cerebral cortex. In addition, the phenothiazines exhibit at least part of their activities through depression of hypothalamic centers. Neurochemically, the phenothiazines are thought to exert their effects by a central adrenergic blocking action.

TargetActionsOrganism
A5-hydroxytryptamine receptor 2A
antagonist
Humans
ADopamine D2 receptor
antagonist
Humans
Absorption

Well absorbed from the gastrointestinal tract.

Volume of distribution

Not Available

Protein binding

4%

Metabolism
Not Available
Route of elimination

Not Available

Half-life

24 to 48 hours

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Oral LD50 is 560 ± 62.5 mg/kg and 644 ± 48 mg/kg in mouse and rat, respectively. Symptoms of overdose may include emesis, muscle tremors, decreased food intake and death associated with aspiration of oral-gastric contents into the respiratory system.

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 Mesoridazine is combined with 1,2-Benzodiazepine.
AbataceptThe metabolism of Mesoridazine can be increased when combined with Abatacept.
AbirateroneThe metabolism of Mesoridazine can be decreased when combined with Abiraterone.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Mesoridazine.
AcenocoumarolThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Acenocoumarol.
AcetaminophenThe metabolism of Mesoridazine can be decreased when combined with Acetaminophen.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Mesoridazine.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Mesoridazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Acetophenazine.
AclidiniumMesoridazine may increase the central nervous system depressant (CNS depressant) activities of Aclidinium.
Interactions
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Food Interactions
  • Take with food. Food reduces irritation.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Mesoridazine besylateT4G2I958J232672-69-8CRJHBCPQHRVYBS-UHFFFAOYSA-N
Mesoridazine mesilateNot AvailableNot AvailableNot applicable
International/Other Brands
Lidanar / Lidanil
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SerentilTablet, film coated100 mg/1OralPhysicians Total Care, Inc.1994-05-182011-06-30US flag
SerentilTablet, film coated10 mg/1OralBoehringer Ingelheim2001-01-242003-06-19US flag
SerentilTablet, film coated100 mg/1OralBoehringer Ingelheim2001-01-242004-01-23US flag
SerentilTablet, film coated50 mg/1OralBoehringer Ingelheim2001-01-242002-05-20US flag
SerentilSolution, concentrate25 mg/1mLOralBoehringer Ingelheim2003-06-192004-01-23US flag
SerentilTablet, film coated25 mg/1OralBoehringer Ingelheim2001-01-242004-01-23US flag
SerentilInjection, suspension25 mg/1mLIntramuscularBoehringer Ingelheim2002-05-202003-06-19US flag
Serentil Tab 10mgTablet10 mg / tabOralNovartis1970-12-312000-08-02Canada flag
Serentil Tab 25mgTablet25 mg / tabOralNovartis1997-08-292001-07-30Canada flag
Serentil Tab 50mgTablet50 mg / tabOralNovartis1997-08-292001-07-30Canada flag

Categories

ATC Codes
N05AC03 — Mesoridazine
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 / Piperidines / Benzenoids / 1,4-thiazines / Trialkylamines / Sulfoxides / Sulfinyl compounds / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
Alkyldiarylamine / Amine / Aromatic heteropolycyclic compound / Aryl thioether / Azacycle / Benzenoid / Diarylthioether / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, tertiary amino compound, sulfoxide (CHEBI:6780)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
5XE4NWM740
CAS number
5588-33-0
InChI Key
SLVMESMUVMCQIY-UHFFFAOYSA-N
InChI
InChI=1S/C21H26N2OS2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(26(2)24)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3
IUPAC Name
2-methanesulfinyl-10-[2-(1-methylpiperidin-2-yl)ethyl]-10H-phenothiazine
SMILES
CN1CCCCC1CCN1C2=C(SC3=C1C=C(C=C3)S(C)=O)C=CC=C2

References

Synthesis Reference
US3084161
General References
Not Available
Human Metabolome Database
HMDB0015068
KEGG Drug
D02671
KEGG Compound
C07143
PubChem Compound
4078
PubChem Substance
46506724
ChemSpider
3936
BindingDB
50131440
RxNav
6779
ChEBI
6780
ChEMBL
CHEMBL1088
Therapeutic Targets Database
DAP000252
PharmGKB
PA450386
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mesoridazine

Clinical Trials

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

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Novartis AG
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
Injection, suspensionIntramuscular25 mg/1mL
Solution, concentrateOral25 mg/1mL
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
TabletOral10 mg / tab
TabletOral25 mg / tab
TabletOral50 mg / tab
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0767 mg/mLALOGPS
logP3.83ALOGPS
logP3.57ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)15.86ChemAxon
pKa (Strongest Basic)8.19ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area23.55 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity115.13 m3·mol-1ChemAxon
Polarizability43.83 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9322
Blood Brain Barrier+0.9863
Caco-2 permeable+0.5609
P-glycoprotein substrateSubstrate0.7284
P-glycoprotein inhibitor IInhibitor0.8978
P-glycoprotein inhibitor IIInhibitor0.5334
Renal organic cation transporterInhibitor0.7467
CYP450 2C9 substrateNon-substrate0.7962
CYP450 2D6 substrateNon-substrate0.5465
CYP450 3A4 substrateSubstrate0.5561
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5635
Ames testNon AMES toxic0.6982
CarcinogenicityNon-carcinogens0.8829
BiodegradationNot ready biodegradable0.9954
Rat acute toxicity2.7465 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7565
hERG inhibition (predictor II)Inhibitor0.762
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0002-9331000000-8e14cb597ee411174c3e
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0119000000-fffe496e2ff640e0c935

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Choi S, Haggart D, Toll L, Cuny GD: Synthesis, receptor binding and functional studies of mesoridazine stereoisomers. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4379-82. [Article]
  2. Rauser L, Savage JE, Meltzer HY, Roth BL: Inverse agonist actions of typical and atypical antipsychotic drugs at the human 5-hydroxytryptamine(2C) receptor. J Pharmacol Exp Ther. 2001 Oct;299(1):83-9. [Article]
  3. Herrick-Davis K, Grinde E, Teitler M: Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors. J Pharmacol Exp Ther. 2000 Oct;295(1):226-32. [Article]
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Burstein ES, Ma J, Wong S, Gao Y, Pham E, Knapp AE, Nash NR, Olsson R, Davis RE, Hacksell U, Weiner DM, Brann MR: Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J Pharmacol Exp Ther. 2005 Dec;315(3):1278-87. Epub 2005 Aug 31. [Article]
  3. Choi S, Haggart D, Toll L, Cuny GD: Synthesis, receptor binding and functional studies of mesoridazine stereoisomers. Bioorg Med Chem Lett. 2004 Sep 6;14(17):4379-82. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Berecz R, de la Rubia A, Dorado P, Fernandez-Salguero P, Dahl ML, LLerena A: Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype. Eur J Clin Pharmacol. 2003 May;59(1):45-50. doi: 10.1007/s00228-003-0576-4. Epub 2003 Mar 28. [Article]
  2. Llerena A, Berecz R, de la Rubia A, Norberto MJ, Benitez J: Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity. Ther Drug Monit. 2000 Aug;22(4):397-401. doi: 10.1097/00007691-200008000-00006. [Article]

Drug created on June 13, 2005 13:24 / Updated on May 07, 2021 21:18