Details of the Drug

General Information of Drug (ID: DMCH80F)

Drug Name
Polythiazide
Synonyms
Drenusil; Nephril; Politiazida; Polythiazidum; Renese; P 2525; P-2525; Politiazida [INN-Spanish]; Polythiazidum [INN-Latin]; Renese (TN); Polythiazide (JAN/USAN/INN); Polythiazide [USAN:INN:BAN:JAN]; 2-Methyl-3-(beta,beta,beta-trifluoroethylthiomethyl)-6-chloro-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide; 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-2-methyl-3-(((2,2,2-trifluoroethyl)thio)methyl)-, 1,1-dioxide; 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-2-methyl-3-(((2,2,2-trifluoroethyl)thio)methyl)-, 1,1-dioxide (8CI, 9CI); 2H-1,2,4-Benzothiadiazine-7-sulfonamide, 6-chloro-3,4-dihydro-2-methyl-3-[[(2,2,2-trifluoroethyl)thio]methyl]-, 1,1-dioxide; 6-Chloro-3,4-dihydro-2-methyl-3-(((2,2,2-trifluoroethyl)thio)methyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 6-Chloro-3,4-dihydro-2-methyl-3-[[(2,2,2-trifluoroethyl)thio]methyl]-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide; 6-Chloro-3,4-dihydro-2-methyl-7-sulphamoyl-3-(2,2,2-trifluoroethylthiomethyl)-2H-benzo-1,2,4-thiadiazine 1,1-dioxide; 6-chloro-2-methyl-1,1-dioxo-3-(2,2,2-trifluoroethylsulfanylmethyl)-3,4-dihydro-1; 6-chloro-2-methyl-3-{[(2,2,2-trifluoroethyl)thio]methyl}-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
Indication
Disease Entry ICD 11 Status REF
Edema MG29 Approved [1]
Hypertension BA00-BA04 Approved [1]
Therapeutic Class
Antihypertensive Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 439.9
Logarithm of the Partition Coefficient (xlogp) 2.6
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 11
ADMET Property
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.13 micromolar/kg/day [2]
Chemical Identifiers
Formula
C11H13ClF3N3O4S3
IUPAC Name
6-chloro-2-methyl-1,1-dioxo-3-(2,2,2-trifluoroethylsulfanylmethyl)-3,4-dihydro-1lambda6,2,4-benzothiadiazine-7-sulfonamide
Canonical SMILES
CN1C(NC2=CC(=C(C=C2S1(=O)=O)S(=O)(=O)N)Cl)CSCC(F)(F)F
InChI
InChI=1S/C11H13ClF3N3O4S3/c1-18-10(4-23-5-11(13,14)15)17-7-2-6(12)8(24(16,19)20)3-9(7)25(18,21)22/h2-3,10,17H,4-5H2,1H3,(H2,16,19,20)
InChIKey
CYLWJCABXYDINA-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
4870
ChEBI ID
CHEBI:8327
CAS Number
346-18-9
DrugBank ID
DB01324
TTD ID
D06TNG
VARIDT ID
DR01033
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Solute carrier family 12 member 3 (SLC12A3) TTP362L S12A3_HUMAN Blocker [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Polythiazide (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Dronedarone DMA8FS5 Major Increased risk of ventricular arrhythmias by the combination of Polythiazide and Dronedarone. Angina pectoris [BA40] [4]
Cariprazine DMJYDVK Moderate Additive hypotensive effects by the combination of Polythiazide and Cariprazine. Bipolar disorder [6A60] [5]
Levomilnacipran DMV26S8 Moderate Increased risk of hyponatremia by the combination of Polythiazide and Levomilnacipran. Chronic pain [MG30] [6]
Vilazodone DM4LECQ Moderate Increased risk of hyponatremia by the combination of Polythiazide and Vilazodone. Depression [6A70-6A7Z] [6]
Vortioxetine DM6F1PU Moderate Increased risk of hyponatremia by the combination of Polythiazide and Vortioxetine. Depression [6A70-6A7Z] [6]
Milnacipran DMBFE74 Moderate Increased risk of hyponatremia by the combination of Polythiazide and Milnacipran. Depression [6A70-6A7Z] [6]
Desvenlafaxine DMHD4PE Moderate Increased risk of hyponatremia by the combination of Polythiazide and Desvenlafaxine. Depression [6A70-6A7Z] [6]
OPC-34712 DMHG57U Moderate Additive hypotensive effects by the combination of Polythiazide and OPC-34712. Depression [6A70-6A7Z] [5]
Mepenzolate DM8YU2F Minor Altered absorption of Polythiazide due to GI dynamics variation caused by Mepenzolate. Digestive system disease [DE2Z] [7]
Eslicarbazepine DMZREFQ Moderate Increased risk of hyponatremia by the combination of Polythiazide and Eslicarbazepine. Epilepsy/seizure [8A61-8A6Z] [8]
Solifenacin DMG592Q Minor Altered absorption of Polythiazide due to GI dynamics variation caused by Solifenacin. Functional bladder disorder [GC50] [7]
Dexlansoprazole DM1DBV5 Moderate Increased risk of hypomagnesemia by the combination of Polythiazide and Dexlansoprazole. Gastro-oesophageal reflux disease [DA22] [9]
Digitoxin DMWVIGP Moderate Increased risk of hypomagnesemia by the combination of Polythiazide and Digitoxin. Heart failure [BD10-BD1Z] [10]
Nebivolol DM7F1PA Moderate Increased risk of ventricular arrhythmias by the combination of Polythiazide and Nebivolol. Hypertension [BA00-BA04] [11]
Belladonna DM2RBWK Minor Altered absorption of Polythiazide due to GI dynamics variation caused by Belladonna. Infectious gastroenteritis/colitis [1A40] [7]
ITI-007 DMUQ1DO Moderate Additive hypotensive effects by the combination of Polythiazide and ITI-007. Insomnia [7A00-7A0Z] [5]
Ozanimod DMT6AM2 Moderate Additive hypotensive effects by the combination of Polythiazide and Ozanimod. Multiple sclerosis [8A40] [12]
Safinamide DM0YWJC Moderate Additive hypotensive effects by the combination of Polythiazide and Safinamide. Parkinsonism [8A00] [12]
Rasagiline DM3WKQ4 Moderate Additive hypotensive effects by the combination of Polythiazide and Rasagiline. Parkinsonism [8A00] [12]
Methylscopolamine DM5VWOB Minor Altered absorption of Polythiazide due to GI dynamics variation caused by Methylscopolamine. Peptic ulcer [DA61] [7]
Levomepromazine DMIKFEL Moderate Additive hypotensive effects by the combination of Polythiazide and Levomepromazine. Psychotic disorder [6A20-6A25] [13]
Iloperidone DM6AUFY Moderate Increased risk of ventricular arrhythmias by the combination of Polythiazide and Iloperidone. Schizophrenia [6A20] [14]
Molindone DMAH70G Moderate Additive hypotensive effects by the combination of Polythiazide and Molindone. Schizophrenia [6A20] [5]
Thiothixene DMDINC4 Moderate Additive hypotensive effects by the combination of Polythiazide and Thiothixene. Schizophrenia [6A20] [5]
Amisulpride DMSJVAM Moderate Increased risk of ventricular arrhythmias by the combination of Polythiazide and Amisulpride. Schizophrenia [6A20] [14]
Asenapine DMSQZE2 Moderate Additive hypotensive effects by the combination of Polythiazide and Asenapine. Schizophrenia [6A20] [5]
⏷ Show the Full List of 26 DDI Information of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7274).
2 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
3 The renal thiazide-sensitive Na-Cl cotransporter as mediator of the aldosterone-escape phenomenon. J Clin Invest. 2001 Jul;108(2):215-22.
4 Product Information. Multaq (dronedarone). sanofi-aventis , Bridgewater, NJ.
5 Aronowitz JS, Chakos MH, Safferman AZ, Lieberman JA "Syncope associated with the combination of clozapine and enalapril." J Clin Psychopharmacol 14 (1994): 429-30. [PMID: 7884028]
6 Product Information. Savella (milnacipran). Forest Pharmaceuticals, St. Louis, MO.
7 Beermann B, Groschinsky-Grind M "Enhancement of the gastrointestinal absorption of hydrochlorothiazide by propantheline." Eur J Clin Pharmacol 13 (1978): 385-7. [PMID: 668798]
8 Product Information. Aptiom (eslicarbazepine). Sunovion Pharmaceuticals Inc, Marlborough, MA.
9 FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".
10 Semple P, Tilstone WJ, Lawson DH "Furosemide and urinary digoxin clearance." N Engl J Med 293 (1975): 612-3. [PMID: 902451]
11 Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33. [PMID: 3987783]
12 Ban TA "Drug interactions with psychoactive drugs." Dis Nerv Syst 36 (1975): 164-6. [PMID: 1116424]
13 Product Information. Clozaril (clozapine). Novartis Pharmaceuticals, East Hanover, NJ.
14 Cerner Multum, Inc. "Australian Product Information.".