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Identification
Name Mesoridazine
Accession Number DB00933 (APRD00610)
Type small molecule
Groups approved
Description

A phenothiazine antipsychotic with effects similar to chlorpromazine. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Thioridazien Thiomethyl Sulfoxide
  • Thioridazine Monosulfoxide Analog
  • Thioridazine Thiomethyl Sulfoxide
  • TPS-23
  • TPS23
Synonyms
Thioridazien Thiomethyl Sulfoxide
Thioridazine Monosulfoxide Analog
Thioridazine Thiomethyl Sulfoxide
TPS-23
TPS23
Salts Not Available
Brand names
Name Company
Calodal
Lidanar
Lidanil
Serentil
Serentil Concentrate
Brand mixtures Not Available
Categories
  • Antipsychotics
  • Dopamine Antagonists
  • Phenothiazines
  • Antipsychotic Agents
CAS number 5588-33-0
Weight Average: 386.574
Monoisotopic: 386.148654844
Chemical Formula C21H26N2OS2
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenothiazines
Substructures
  • Ethers
  • Phenothiazines
  • Aliphatic and Aryl Amines
  • Thiazines
  • Benzene and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
  • Sulfoxides
  • Piperidines
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.
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
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Injection, solution Intramuscular
Tablet Oral
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 3.9 PhysProp
Predicted Properties
Property Value Source
water solubility 7.67e-02 g/l ALOGPS
logP 3.83 ALOGPS
logP 3.57 ChemAxon Molconvert
logS -3.7 ALOGPS
pKa 0 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 23.55 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 115.13 ChemAxon Molconvert
polarizability 43.83 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02671 Link_out
KEGG Compound C07143 Link_out
PubChem Compound 4078 Link_out
PubChem Substance 46506724 Link_out
ChemSpider 3936 Link_out
BindingDB 50131440 Link_out
ChEBI 6780 Link_out
ChEMBL 6780 Link_out
Therapeutic Targets Database DAP000252 Link_out
PharmGKB PA450386 Link_out
Drug Product Database 27464 Link_out
RxList http://www.rxlist.com/cgi/generic3/mesoridazine.htm Link_out
Drugs.com http://www.drugs.com/mtm/mesoridazine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mesoridazine Link_out
ATC Codes
  • N05AC03
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Amitriptyline Increased risk of cardiotoxicity and arrhythmias
Amphetamine Decreased anorexic effect, may increase psychotic symptoms
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Astemizole Increased risk of cardiotoxicity and arrhythmias
Benzphetamine Antipsychotics may diminish the stimulatory effect of Amphetamines. Monitor effectiveness of amphetamine therapy when altering concurrent antipsychotic therapy as antipsychotic agents may impair the stimulatory effect of amphetamines.
Bretylium Increased risk of cardiotoxicity and arrhythmias
Bromocriptine The phenothiazine decreases the effect of bromocriptine
Chloroquine Increased risk of cardiotoxicity and arrhythmias
Chlorpromazine Increased risk of cardiotoxicity and arrhythmias
Cisapride Increased risk of cardiotoxicity and arrhythmias
Dexfenfluramine Decreased anorexic effect, may increase psychotic symptoms
Dextroamphetamine Decreased anorexic effect, may increase psychotic symptoms
Diethylpropion Decreased anorexic effect, may increase psychotic symptoms
Diltiazem Increased risk of cardiotoxicity and arrhythmias
Diphenhydramine Increased risk of cardiotoxicity and arrhythmias
Disopyramide Increased risk of cardiotoxicity and arrhythmias
Dofetilide Increased risk of cardiotoxicity and arrhythmias
Donepezil Possible antagonism of action
Doxepin Increased risk of cardiotoxicity and arrhythmias
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Fenfluramine Decreased anorexic effect, may increase psychotic symptoms
Flecainide Increased risk of cardiotoxicity and arrhythmias
Fluoxetine Increased risk of cardiotoxicity and arrhythmias
Fluvoxamine Increased risk of cardiotoxicity and arrhythmias
Galantamine Possible antagonism of action
Gatifloxacin Increased risk of cardiotoxicity and arrhythmias
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine Mesoridazine may decrease the effect of guanethidine.
Halofantrine Increased risk of cardiotoxicity and arrhythmias
Haloperidol Increased risk of cardiotoxicity and arrhythmias
Imipramine Increased risk of cardiotoxicity and arrhythmias
Josamycin Increased risk of cardiotoxicity and arrhythmias
Levofloxacin Increased risk of cardiotoxicity and arrhythmias
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Maprotiline Increased risk of cardiotoxicity and arrhythmias
Mazindol Decreased anorexic effect, may increase psychotic symptoms
Methamphetamine Decreased anorexic effect, may increase psychotic symptoms
Metrizamide Increased risk of cardiotoxicity and arrhythmias
Paroxetine Increased risk of cardiotoxicity and arrhythmias
Penicillin G Increased risk of cardiotoxicity and arrhythmias
Pentamidine Increased risk of cardiotoxicity and arrhythmias
Phendimetrazine Decreased anorexic effect, may increase psychotic symptoms
Phenmetrazine Decreased anorexic effect, may increase psychotic symptoms
Phentermine Decreased anorexic effect, may increase psychotic symptoms
Phenylpropanolamine Decreased anorexic effect, may increase psychotic symptoms
Pimozide Increased risk of cardiotoxicity and arrhythmias
Pindolol Increased risk of cardiotoxicity and arrhythmias
Procainamide Increased risk of cardiotoxicity and arrhythmias
Propafenone Increased risk of cardiotoxicity and arrhythmias.
Propranolol Increased risk of cardiotoxicity and arrhythmias
Quinidine Increased risk of cardiotoxicity and arrhythmias
Quinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Quinine Increased risk of cardiotoxicity and arrhythmias
Rivastigmine Possible antagonism of action
Sertindole Increased risk of cardiotoxicity and arrhythmias
Sotalol Increased risk of cardiotoxicity and arrhythmias
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Spiramycin Increased risk of cardiotoxicity and arrhythmias
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Mesoridazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tetrabenazine May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimethobenzamide Trimethobenzamide and Mesoridazine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine The antihistamine, Triprolidine, may increase the arrhythmogenic effect of the phenothiazine, Mesoridazine. Monitor for symptoms of ventricular arrhythmias. Additive anticholinergic and CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Trospium Trospium and Mesoridazine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Take with food to reduce irritation.
Targets

1. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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

2. D(2) dopamine receptor

Pharmacological action: yes
Actions: antagonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out
Gene: DRD2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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
  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
Enzymes

1. Cytochrome P450 2D6

Actions: substrate

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

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 14, 2012 11:44