Methyclothiazide

Identification

Summary

Methyclothiazide is a diuretic drug used to treat hypertension and edema caused by heart failure, renal conditions, treatment with corticosteroids, and estrogen therapy.

Generic Name
Methyclothiazide
DrugBank Accession Number
DB00232
Background

A thiazide diuretic with properties similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p825)

Type
Small Molecule
Groups
Withdrawn
Structure
Weight
Average: 360.237
Monoisotopic: 358.956802649
Chemical Formula
C9H11Cl2N3O4S2
Synonyms
  • Methyclothiazide

Pharmacology

Indication

For use in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension. Also used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofEdema••••••••••••
Adjunct therapy in treatment ofEdema••••••••••••
Adjunct therapy in treatment ofEdema••••••••••••
Adjunct therapy in treatment ofEdema••••••••••••
Adjunct therapy in treatment ofEdema••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Methyclothiazide, a diuretic-antihypertensive agent, is a member of the benzothiadiazine (thiazide) class of drugs. Methyclothiazide has a per mg natriuretic activity approximately 100 times that of the prototype thiazide, chlorothiazide. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic/natriuretic effects. Like other benzothiadiazines, methyclothiazide also has antihypertensive properties, and may be used for this purpose either alone or to enhance the antihypertensive action of other drugs.

Mechanism of action

Methyclothiazide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis. As a diuretic, methyclothiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like methyclothiazide 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 methyclothiazide is less well understood although it 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 1
inhibitor
Humans
UCarbonic anhydrase 1
inhibitor
Humans
UCarbonic anhydrase 2
inhibitor
Humans
UCarbonic anhydrase 4
inhibitor
Humans
Absorption

Rapidly absorbed following oral administration.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Acute oral toxicity (LD50): >4000 mg/kg [Rat]. Symptoms of overdosage include electrolyte imbalance and signs of potassium deficiency such as confusion, dizziness, muscular weakness, and gastrointestinal disturbances.

Pathways
PathwayCategory
Methyclothiazide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirMethyclothiazide may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbaloparatideThe risk or severity of adverse effects can be increased when Methyclothiazide is combined with Abaloparatide.
AbciximabThe therapeutic efficacy of Abciximab can be decreased when used in combination with Methyclothiazide.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Methyclothiazide.
AcebutololThe therapeutic efficacy of Acebutolol can be increased when used in combination with Methyclothiazide.
Food Interactions
Not Available

Products

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International/Other Brands
Aquatensen / Duretic / Enduron
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Duretic 5mgTablet5 mgOralAbbott1960-12-311999-08-09Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MethyclothiazideTablet5 mg/1OralMylan Pharmaceuticals Inc.1982-08-172019-12-31US flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
EnduronylMethyclothiazide (5 mg/1) + Deserpidine (0.25 mg/1)TabletOralAbbvie1961-08-012002-04-30US flag
EnduronylMethyclothiazide (5 mg/1) + Deserpidine (0.25 mg/1)TabletOralPhysicians Total Care, Inc.1961-08-012006-12-31US flag
Enduronyl ForteMethyclothiazide (5 mg/1) + Deserpidine (0.5 mg/1)TabletOralAbbvie1961-08-012001-04-30US flag

Categories

ATC Codes
C03AA08 — MethyclothiazideC03AB08 — Methyclothiazide and potassium
Drug Categories
Chemical TaxonomyProvided by Classyfire
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 / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
1,2,4-benzothiadiazine-1,1-dioxide / Alkyl chloride / Alkyl halide / Amine / Aminosulfonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzothiadiazine (CHEBI:6847)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
L3H46UAC61
CAS number
135-07-9
InChI Key
CESYKOGBSMNBPD-UHFFFAOYSA-N
InChI
InChI=1S/C9H11Cl2N3O4S2/c1-14-9(4-10)13-6-2-5(11)7(19(12,15)16)3-8(6)20(14,17)18/h2-3,9,13H,4H2,1H3,(H2,12,15,16)
IUPAC Name
6-chloro-3-(chloromethyl)-2-methyl-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
SMILES
CN1C(CCl)NC2=CC(Cl)=C(C=C2S1(=O)=O)S(N)(=O)=O

References

General References
Not Available
Human Metabolome Database
HMDB0014377
KEGG Drug
D00656
KEGG Compound
C07765
PubChem Compound
4121
PubChem Substance
46509197
ChemSpider
3978
RxNav
6860
ChEBI
6847
ChEMBL
CHEMBL1577
Therapeutic Targets Database
DAP000746
PharmGKB
PA164748094
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Methyclothiazide
MSDS
Download (74.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Medpointe pharmaceuticals medpointe healthcare inc
  • Abbott laboratories pharmaceutical products div
  • Ivax pharmaceuticals inc
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Sandoz inc
  • Usl pharma inc
  • Watson laboratories inc
Packagers
  • Ivax Pharmaceuticals
  • Medisca Inc.
  • Mylan
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Sandhills Packaging Inc.
Dosage Forms
FormRouteStrength
TabletOral5 mg
TabletOral
TabletOral5 mg/1
Prices
Unit descriptionCostUnit
Methyclothiazide powder11.32USD g
Enduron 5 mg tablet0.77USD tablet
Methyclothiazide 5 mg tablet0.77USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)225 °CPhysProp
water solubility11.2 mg/LNot Available
logP1.42HANSCH,C ET AL. (1995)
pKa9.4MERCK INDEX (2001)
Predicted Properties
PropertyValueSource
Water Solubility0.824 mg/mLALOGPS
logP0.93ALOGPS
logP0.53Chemaxon
logS-2.6ALOGPS
pKa (Strongest Acidic)9.29Chemaxon
pKa (Strongest Basic)-3.4Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area109.57 Å2Chemaxon
Rotatable Bond Count2Chemaxon
Refractivity77.28 m3·mol-1Chemaxon
Polarizability31.65 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9834
Blood Brain Barrier-0.6866
Caco-2 permeable-0.6992
P-glycoprotein substrateSubstrate0.5317
P-glycoprotein inhibitor INon-inhibitor0.8518
P-glycoprotein inhibitor IINon-inhibitor0.8888
Renal organic cation transporterNon-inhibitor0.8177
CYP450 2C9 substrateNon-substrate0.631
CYP450 2D6 substrateNon-substrate0.8261
CYP450 3A4 substrateNon-substrate0.532
CYP450 1A2 substrateNon-inhibitor0.6883
CYP450 2C9 inhibitorNon-inhibitor0.6493
CYP450 2D6 inhibitorNon-inhibitor0.858
CYP450 2C19 inhibitorNon-inhibitor0.808
CYP450 3A4 inhibitorInhibitor0.5094
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7345
Ames testNon AMES toxic0.8905
CarcinogenicityNon-carcinogens0.82
BiodegradationNot ready biodegradable0.9971
Rat acute toxicity1.9853 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9384
hERG inhibition (predictor II)Non-inhibitor0.9318
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-MSsplash10-0lfu-3194000000-3a8ed7eb146b4c09f0bc
GC-MS Spectrum - EI-BGC-MSsplash10-03di-9312000000-ae6f36f61e1e3b835a9f
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-00ri-0493000000-a1b477251688af0d67e8
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00ri-0493000000-a1b477251688af0d67e8
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-9775c90f8a613f5b81f1
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-d9e07f5605e5b6d977ca
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-4696082d994817ef13c0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-0009000000-bbbc12272ebba93f0a29
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0h4p-0393000000-b184b24582c14a9c7df5
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00c0-9022000000-c331b5da0336f614c3e9
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-170.7063754
predicted
DarkChem Lite v0.1.0
[M-H]-170.4978
predicted
DeepCCS 1.0 (2019)
[M+H]+171.1539754
predicted
DarkChem Lite v0.1.0
[M+H]+172.8558
predicted
DeepCCS 1.0 (2019)
[M+Na]+170.8906754
predicted
DarkChem Lite v0.1.0
[M+Na]+178.94896
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sodium:potassium:chloride symporter activity
Specific Function
Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
Gene Name
SLC12A1
Uniprot ID
Q13621
Uniprot Name
Solute carrier family 12 member 1
Molecular Weight
121449.13 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name
CA1
Uniprot ID
P00915
Uniprot Name
Carbonic anhydrase 1
Molecular Weight
28870.0 Da
References
  1. Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [Article]
  2. Couloigner V, Loiseau A, Sterkers O, Amiel C, Ferrary E: Effect of locally applied drugs on the endolymphatic sac potential. Laryngoscope. 1998 Apr;108(4 Pt 1):592-8. [Article]
  3. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion in...
Gene Name
CA2
Uniprot ID
P00918
Uniprot Name
Carbonic anhydrase 2
Molecular Weight
29245.895 Da
References
  1. Meyerson LR, Nesta D: [3H]acetazolamide binding to carbonic anhydrase in normal and transformed cells. Biochem Pharmacol. 1991 Mar 15-Apr 1;41(6-7):995-1000. [Article]
  2. Schaeffer P, Vigne P, Frelin C, Lazdunski M: Identification and pharmacological properties of binding sites for the atypical thiazide diuretic, indapamide. Eur J Pharmacol. 1990 Jul 17;182(3):503-8. [Article]
  3. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina an...
Gene Name
CA4
Uniprot ID
P22748
Uniprot Name
Carbonic anhydrase 4
Molecular Weight
35032.075 Da
References
  1. Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [Article]
  2. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [Article]

Drug created at June 13, 2005 13:24 / Updated at January 02, 2024 23:43