Identification

Name
Mesoridazine
Accession Number
DB00933  (APRD00610)
Type
Small Molecule
Groups
Approved, Investigational
Description

A phenothiazine antipsychotic with effects similar to chlorpromazine.

Structure
Thumb
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
  • Mesoridazinum
  • Thioridazine 2-sulfoxide
  • Thioridazine thiomethyl sulfoxide
  • Thioridazine-2-sulfoxide
External IDs
NC-123 / TPS-23
Product Ingredients
IngredientUNIICASInChI Key
Mesoridazine besylateT4G2I958J232672-69-8CRJHBCPQHRVYBS-UHFFFAOYSA-N
Mesoridazine mesilateNot AvailableNot AvailableNot applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SerentilTablet, film coated100 mg/1OralBoehringer Ingelheim2001-01-242004-01-23Us
SerentilTablet, film coated50 mg/1OralBoehringer Ingelheim2001-01-242002-05-20Us
SerentilSolution, concentrate25 mg/1mLOralBoehringer Ingelheim2003-06-192004-01-23Us
SerentilTablet, film coated25 mg/1OralBoehringer Ingelheim2001-01-242004-01-23Us
SerentilInjection, suspension25 mg/1mLIntramuscularBoehringer Ingelheim2002-05-202003-06-19Us
SerentilTablet, film coated100 mg/1OralPhysicians Total Care, Inc.1994-05-182011-06-30Us
SerentilTablet, film coated10 mg/1OralBoehringer Ingelheim2001-01-242003-06-19Us
Serentil Tab 10mgTablet10 mgOralNovartis1970-12-312000-08-02Canada
Serentil Tab 25mgTablet25 mgOralNovartis1997-08-292001-07-30Canada
Serentil Tab 50mgTablet50 mgOralNovartis1997-08-292001-07-30Canada
International/Other Brands
Lidanar / Lidanil / Serentil
Categories
UNII
5XE4NWM740
CAS number
5588-33-0
Weight
Average: 386.574
Monoisotopic: 386.148654844
Chemical Formula
C21H26N2OS2
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

Pharmacology

Indication

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

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
Human
AD(2) dopamine receptor
antagonist
Human
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
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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Mesoridazine is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Mesoridazine is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineMesoridazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineMesoridazine may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Mesoridazine.
3,5-DinitrocatecholThe therapeutic efficacy of 3,5-Dinitrocatechol can be decreased when used in combination with Mesoridazine.
4-Bromo-2,5-dimethoxyamphetamineMesoridazine may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of adverse effects can be increased when Mesoridazine is combined with 4-hydroxycoumarin.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Mesoridazine is combined with 7-Nitroindazole.
AbexinostatThe risk or severity of QTc prolongation can be increased when Mesoridazine is combined with Abexinostat.
Food Interactions
  • Take with food to reduce irritation.

References

Synthesis Reference
US3084161
General References
Not Available
External Links
Human Metabolome Database
HMDB0015068
KEGG Drug
D02671
KEGG Compound
C07143
PubChem Compound
4078
PubChem Substance
46506724
ChemSpider
3936
BindingDB
50131440
ChEBI
6780
ChEMBL
CHEMBL1088
Therapeutic Targets Database
DAP000252
PharmGKB
PA450386
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mesoridazine
ATC Codes
N05AC03 — Mesoridazine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableBipolar Disorder (BD) / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / 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
TabletOral25 mg
TabletOral50 mg
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

Taxonomy

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
Phenothiazine / Alkyldiarylamine / Diarylthioether / Aryl thioether / Tertiary aliphatic/aromatic amine / Para-thiazine / Piperidine / Benzenoid / Sulfoxide / Tertiary amine
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
phenothiazines, tertiary amino compound, sulfoxide (CHEBI:6780)

Targets

Kind
Protein
Organism
Human
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. [PubMed:15357957]
  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. [PubMed:11561066]
  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. [PubMed:10991983]
Kind
Protein
Organism
Human
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. [PubMed:11752352]
  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. [PubMed:16135699]
  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. [PubMed:15357957]

Enzymes

Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. 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. [PubMed:12682803]

Drug created on June 13, 2005 07:24 / Updated on October 10, 2018 21:49