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Identification
NameMesoridazine
Accession NumberDB00933  (APRD00610)
TypeSmall Molecule
GroupsApproved
Description

A phenothiazine antipsychotic with effects similar to chlorpromazine. [PubChem]

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
Mesoridazine
Mesoridazinum
Thioridazine Thiomethyl Sulfoxide
thioridazine-2-sulfoxide
TPS-23
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Serentil Tab 10mgtablet10 mgoralNovartis Pharmaceuticals Canada Inc1970-12-312000-08-02Canada
Serentil Tab 25mgtablet25 mgoralNovartis Pharmaceuticals Canada Inc1997-08-292001-07-30Canada
Serentil Tab 50mgtablet50 mgoralNovartis Pharmaceuticals Canada Inc1997-08-292001-07-30Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LidanarNot Available
LidanilNot Available
SerentilNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Mesoridazine besylate
ThumbNot applicableDBSALT001396
Mesoridazine mesilate
ThumbNot applicableDBSALT001073
Categories
UNII5XE4NWM740
CAS number5588-33-0
WeightAverage: 386.574
Monoisotopic: 386.148654844
Chemical FormulaC21H26N2OS2
InChI KeyInChIKey=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=CC=CC=C2SC2=C1C=C(C=C2)S(C)=O
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiazines
Sub ClassPhenothiazines
Direct ParentPhenothiazines
Alternative Parents
Substituents
  • Phenothiazine
  • Alkyldiarylamine
  • Diarylthioether
  • Benzenoid
  • Piperidine
  • Para-thiazine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Sulfoxide
  • Azacycle
  • Sulfinyl compound
  • Thioether
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed in the treatment of schizophrenia, organic brain disorders, alcoholism and psychoneuroses.
PharmacodynamicsMesoridazine, 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 actionBased 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.
Related Articles
AbsorptionWell absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein binding4%
MetabolismNot Available
Route of eliminationNot Available
Half life24 to 48 hours
ClearanceNot Available
ToxicityOral 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
Tabletoral10 mg
Tabletoral25 mg
Tabletoral50 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP3.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0767 mg/mLALOGPS
logP3.83ALOGPS
logP3.57ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)19.36ChemAxon
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 RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0002-9331000000-8e14cb597ee411174c3eView in MoNA
References
Synthesis Reference

DrugSyn.org

US3084161
General ReferencesNot Available
External Links
ATC CodesN05AC03
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AlmotriptanThe risk or severity of adverse effects can be increased when Almotriptan is combined with Mesoridazine.
AmitriptylineThe risk or severity of adverse effects can be increased when Amitriptyline is combined with Mesoridazine.
AmoxapineThe risk or severity of adverse effects can be increased when Amoxapine is combined with Mesoridazine.
AmphetamineMesoridazine may decrease the stimulatory activities of Amphetamine.
BenzphetamineMesoridazine may decrease the stimulatory activities of Benzphetamine.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Mesoridazine.
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Mesoridazine.
CitalopramThe risk or severity of adverse effects can be increased when Citalopram is combined with Mesoridazine.
ClomipramineThe risk or severity of adverse effects can be increased when Clomipramine is combined with Mesoridazine.
CyclobenzaprineThe risk or severity of adverse effects can be increased when Cyclobenzaprine is combined with Mesoridazine.
DesipramineThe risk or severity of adverse effects can be increased when Desipramine is combined with Mesoridazine.
DesvenlafaxineThe risk or severity of adverse effects can be increased when Desvenlafaxine is combined with Mesoridazine.
DextroamphetamineMesoridazine may decrease the stimulatory activities of Dextroamphetamine.
DextromethorphanThe risk or severity of adverse effects can be increased when Dextromethorphan is combined with Mesoridazine.
DihydroergotamineThe risk or severity of adverse effects can be increased when Dihydroergotamine is combined with Mesoridazine.
DonepezilDonepezil may increase the central neurotoxic activities of Mesoridazine.
DoxepinThe risk or severity of adverse effects can be increased when Doxepin is combined with Mesoridazine.
DuloxetineThe risk or severity of adverse effects can be increased when Duloxetine is combined with Mesoridazine.
EletriptanThe risk or severity of adverse effects can be increased when Eletriptan is combined with Mesoridazine.
Ergoloid mesylateThe risk or severity of adverse effects can be increased when Ergoloid mesylate is combined with Mesoridazine.
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Mesoridazine.
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Mesoridazine.
EscitalopramThe risk or severity of adverse effects can be increased when Escitalopram is combined with Mesoridazine.
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Mesoridazine.
FluoxetineThe risk or severity of adverse effects can be increased when Fluoxetine is combined with Mesoridazine.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Mesoridazine.
FrovatriptanThe risk or severity of adverse effects can be increased when Frovatriptan is combined with Mesoridazine.
GalantamineGalantamine may increase the central neurotoxic activities of Mesoridazine.
ImipramineThe risk or severity of adverse effects can be increased when Imipramine is combined with Mesoridazine.
IsocarboxazidThe risk or severity of adverse effects can be increased when Isocarboxazid is combined with Mesoridazine.
LevomilnacipranThe risk or severity of adverse effects can be increased when Levomilnacipran is combined with Mesoridazine.
LinezolidThe risk or severity of adverse effects can be increased when Linezolid is combined with Mesoridazine.
LisdexamfetamineMesoridazine may decrease the stimulatory activities of Lisdexamfetamine.
LithiumLithium may increase the neurotoxic activities of Mesoridazine.
LorcaserinThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Mesoridazine.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Mesoridazine.
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Mesoridazine.
MethamphetamineMesoridazine may decrease the stimulatory activities of Methamphetamine.
MethylphenidateThe risk or severity of adverse effects can be increased when Mesoridazine is combined with Methylphenidate.
MetoclopramideThe risk or severity of adverse effects can be increased when Metoclopramide is combined with Mesoridazine.
MetyrosineThe risk or severity of adverse effects can be increased when Metyrosine is combined with Mesoridazine.
MilnacipranThe risk or severity of adverse effects can be increased when Milnacipran is combined with Mesoridazine.
MoclobemideThe risk or severity of adverse effects can be increased when Moclobemide is combined with Mesoridazine.
NaratriptanThe risk or severity of adverse effects can be increased when Naratriptan is combined with Mesoridazine.
NefazodoneThe risk or severity of adverse effects can be increased when Nefazodone is combined with Mesoridazine.
NortriptylineThe risk or severity of adverse effects can be increased when Nortriptyline is combined with Mesoridazine.
ParoxetineThe risk or severity of adverse effects can be increased when Paroxetine is combined with Mesoridazine.
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Mesoridazine.
PhendimetrazineMesoridazine may decrease the stimulatory activities of Phendimetrazine.
PhenelzineThe risk or severity of adverse effects can be increased when Phenelzine is combined with Mesoridazine.
PhentermineMesoridazine may decrease the stimulatory activities of Phentermine.
ProcarbazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Mesoridazine.
PromethazineThe risk or severity of adverse effects can be increased when Promethazine is combined with Mesoridazine.
ProtriptylineThe risk or severity of adverse effects can be increased when Protriptyline is combined with Mesoridazine.
QuinagolideThe therapeutic efficacy of Quinagolide can be decreased when used in combination with Mesoridazine.
RasagilineThe risk or severity of adverse effects can be increased when Rasagiline is combined with Mesoridazine.
RivastigmineRivastigmine may increase the central neurotoxic activities of Mesoridazine.
RizatriptanThe risk or severity of adverse effects can be increased when Rizatriptan is combined with Mesoridazine.
SelegilineThe risk or severity of adverse effects can be increased when Selegiline is combined with Mesoridazine.
SertralineThe risk or severity of adverse effects can be increased when Sertraline is combined with Mesoridazine.
SumatriptanThe risk or severity of adverse effects can be increased when Sumatriptan is combined with Mesoridazine.
Tedizolid PhosphateThe risk or severity of adverse effects can be increased when Tedizolid Phosphate is combined with Mesoridazine.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Mesoridazine.
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Mesoridazine.
TranylcypromineThe risk or severity of adverse effects can be increased when Tranylcypromine is combined with Mesoridazine.
TrazodoneThe risk or severity of adverse effects can be increased when Trazodone is combined with Mesoridazine.
TrimipramineThe risk or severity of adverse effects can be increased when Trimipramine is combined with Mesoridazine.
VenlafaxineThe risk or severity of adverse effects can be increased when Venlafaxine is combined with Mesoridazine.
VilazodoneThe risk or severity of adverse effects can be increased when Vilazodone is combined with Mesoridazine.
VortioxetineThe risk or severity of adverse effects can be increased when Vortioxetine is combined with Mesoridazine.
ZolmitriptanThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Mesoridazine.
Food Interactions
  • Take with food to reduce irritation.

Targets

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
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 ]
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-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
Gene Name:
HTR2A
Uniprot ID:
P28223
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 ]

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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
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 ]
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Drug created on June 13, 2005 07:24 / Updated on November 27, 2015 16:49