Identification

Name
Polythiazide
Accession Number
DB01324
Type
Small Molecule
Groups
Approved
Description

A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p826)

Structure
Thumb
Synonyms
Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ReneseTablet1 mg/1OralPfizer Labs2005-12-14Not applicableUs
ReneseTablet4 mg/1OralPfizer Labs2005-12-14Not applicableUs
ReneseTablet2 mg/1OralPfizer Labs2005-12-14Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
MinizidePolythiazide (0.5 mg/1) + Prazosin Hydrochloride (5 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUs
MinizidePolythiazide (0.5 mg/1) + Prazosin Hydrochloride (2 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUs
MinizidePolythiazide (0.5 mg/1) + Prazosin Hydrochloride (1 mg/1)CapsuleOralPfizer Labs2006-10-05Not applicableUs
Renese-RPolythiazide (2 mg/1) + Reserpine (25 mg/1)TabletOralUNSPECIFIED2006-02-06Not applicableUs
International/Other Brands
Renese
Categories
UNII
36780APV5N
CAS number
346-18-9
Weight
Average: 439.882
Monoisotopic: 438.970880311
Chemical Formula
C11H13ClF3N3O4S3
InChI Key
CYLWJCABXYDINA-UHFFFAOYSA-N
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)
IUPAC Name
6-chloro-2-methyl-1,1-dioxo-3-{[(2,2,2-trifluoroethyl)sulfanyl]methyl}-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
SMILES
CN1C(CSCC(F)(F)F)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O

Pharmacology

Indication

Polythiazide is a thiazide diuretic used to decrease edema and decrease blood pressure.

Pharmacodynamics

As a thiazide diuretic, Polythiazide inhibits the sodium-chloride symporter which decreases solute reabsorption leading to a retention of water in the urine, as water normally follows solutes. More frequent urination is due to the increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule. The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure

Mechanism of action

As a diuretic, polythiazide inhibits active chloride reabsorption at the early distal tubule via the thiazide-sensitive Na-Cl cotransporter (TSC), resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like polythiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of polythiazide may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle.

TargetActionsOrganism
ASolute carrier family 12 member 3
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Polythiazide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINEThe therapeutic efficacy of (1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE can be decreased when used in combination with Polythiazide.
(4R)-limoneneThe therapeutic efficacy of Polythiazide can be decreased when used in combination with (4R)-limonene.
16-Bromoepiandrosterone16-Bromoepiandrosterone may increase the hypokalemic activities of Polythiazide.
19-norandrostenedione19-norandrostenedione may increase the hypokalemic activities of Polythiazide.
1alpha-Hydroxyvitamin D5The risk or severity of hyperkalemia can be increased when 1alpha-Hydroxyvitamin D5 is combined with Polythiazide.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Polythiazide.
5-androstenedione5-androstenedione may increase the hypokalemic activities of Polythiazide.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Polythiazide.
AbediterolAbediterol may increase the hypokalemic activities of Polythiazide.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Polythiazide.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015419
KEGG Drug
D00657
KEGG Compound
C07766
PubChem Compound
4870
PubChem Substance
46508633
ChemSpider
4704
ChEBI
8327
ChEMBL
CHEMBL1587
Therapeutic Targets Database
DAP000751
PharmGKB
PA164748763
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Polythiazide
ATC Codes
C03AA05 — PolythiazideC03AB05 — Polythiazide and potassiumG01AE10 — Combinations of sulfonamides

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Pfizer Inc.
Dosage forms
FormRouteStrength
CapsuleOral
TabletOral1 mg/1
TabletOral2 mg/1
TabletOral4 mg/1
TabletOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)214 °CPhysProp
logP1.90SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.264 mg/mLALOGPS
logP2.13ALOGPS
logP1.1ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)9.31ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area109.57 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity90.52 m3·mol-1ChemAxon
Polarizability37.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9884
Blood Brain Barrier-0.5727
Caco-2 permeable-0.6601
P-glycoprotein substrateSubstrate0.6985
P-glycoprotein inhibitor INon-inhibitor0.7714
P-glycoprotein inhibitor IINon-inhibitor0.8974
Renal organic cation transporterNon-inhibitor0.776
CYP450 2C9 substrateNon-substrate0.6019
CYP450 2D6 substrateNon-substrate0.8108
CYP450 3A4 substrateNon-substrate0.5091
CYP450 1A2 substrateNon-inhibitor0.7786
CYP450 2C9 inhibitorNon-inhibitor0.5713
CYP450 2D6 inhibitorNon-inhibitor0.8479
CYP450 2C19 inhibitorNon-inhibitor0.7738
CYP450 3A4 inhibitorInhibitor0.6198
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6625
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8224
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.3534 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8884
hERG inhibition (predictor II)Non-inhibitor0.8734
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
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Thiadiazines
Sub Class
Benzothiadiazines
Direct Parent
1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Secondary alkylarylamines / Organosulfonamides / Benzenoids / Aryl chlorides / Aminosulfonyl compounds / Sulfenyl compounds / Dialkylthioethers / Azacyclic compounds / Organopnictogen compounds / Organofluorides
show 4 more
Substituents
1,2,4-benzothiadiazine-1,1-dioxide / Secondary aliphatic/aromatic amine / Aryl chloride / Aryl halide / Organosulfonic acid amide / Benzenoid / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl / Aminosulfonyl compound
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzothiadiazine (CHEBI:8327)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
Gene Name
SLC12A3
Uniprot ID
P55017
Uniprot Name
Solute carrier family 12 member 3
Molecular Weight
113138.04 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. Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. [PubMed:10894798]
  3. Frindt G, McNair T, Dahlmann A, Jacobs-Palmer E, Palmer LG: Epithelial Na channels and short-term renal response to salt deprivation. Am J Physiol Renal Physiol. 2002 Oct;283(4):F717-26. [PubMed:12217863]

Drug created on June 30, 2007 11:21 / Updated on October 01, 2018 13:02