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Identification
Name Methyclothiazide
Accession Number DB00232 (APRD01104)
Type small molecule
Groups approved
Description

A thiazide diuretic with properties similar to those of hydrochlorothiazide. (From Martindale, The Extra Pharmacopoeia, 30th ed, p825)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Methychlothiazide
  • Methyclothiazid
  • Methycyclothiazide
  • Methylchlorothiazide
  • Methylclothiazide
  • Methylcyclothiazide
Brand names
  • Aquaresen
  • Aquatensen
  • Duretic
  • Enduron
  • Enduronum
Brand name mixtures Not Available
Categories
  • Diuretics
  • Diuretics, Thiazide
  • Sodium Chloride Symporter Inhibitors
CAS number 135-07-9
Weight Average: 360.237
Monoisotopic: 358.956802649
Chemical Formula C9H11Cl2N3O4S2
InChI Key InChIKey=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)
Plain Text
IUPAC Name
6-chloro-3-(chloromethyl)-2-methyl-1,1-dioxo-3,4-dihydro-2H-1$l^{6},2,4-benzothiadiazine-7-sulfonamide
SMILES
CN1C(CCl)NC2=C(C=C(C(Cl)=C2)S(N)(=O)=O)S1(=O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzenesulfonamides
  • Sulfanilamides
Substructures
  • Sulfonyls
  • Benzene and Derivatives
  • Aryl Halides
  • Benzenesulfonamides
  • Halobenzenes
  • Aminals and Derivatives
  • Alkyl Halides
  • Heterocyclic compounds
  • Aromatic compounds
  • Thiadiazines
  • Sulfanilamides
  • Sulfonamides
  • Anilines
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.
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.
Absorption Rapidly absorbed following oral administration.
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Route of elimination Not Available
Half life Not Available
Clearance Not Available
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.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00081 Methyclothiazide Pathway SMP00081
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
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Methyclothiazide powder 11.32 USD g
Enduron 5 mg tablet 0.77 USD tablet
Methyclothiazide 5 mg tablet 0.77 USD tablet
Patents Not Available
Properties
State solid
Melting point 225 oC
Experimental Properties
Property Value Source
water solubility 11.2 mg/L PhysProp
logP 0.6 PhysProp
pKa 9.4 Various sources
Predicted Properties
Property Value Source
water solubility 8.24e-01 g/l ALOGPS
logP 0.93 ALOGPS
logP 0.53 ChemAxon Molconvert
logS -2.64 ALOGPS
pKa 10.54 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 109.57 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 77.28 ChemAxon Molconvert
polarizability 31.65 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00656 Link_out
KEGG Compound C07765 Link_out
PubChem Compound 4121 Link_out
PubChem Substance 46509197 Link_out
ChemSpider 3978 Link_out
Therapeutic Targets Database DAP000746 Link_out
PharmGKB PA450439 Link_out
Drug Product Database 485 Link_out
RxList http://www.rxlist.com/cgi/generic3/methyclothiazide.htm Link_out
Drugs.com http://www.drugs.com/cdi/methyclothiazide.html Link_out
ATC Codes
  • C03AA08
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (74.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Solute carrier family 12 member 1

Pharmacological action: yes
Actions: inhibitor

Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume

Organism class: human
UniProt ID: Q13621 Link_out
Gene: SLC12A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Carbonic anhydrase 1

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00915 Link_out
Gene: CA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Epub 2008 Dec 24. Pubmed

3. Carbonic anhydrase 2

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide

Organism class: human
UniProt ID: P00918 Link_out
Gene: CA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Epub 2008 Dec 24. Pubmed

4. Carbonic anhydrase 4

Pharmacological action: unknown
Actions: inhibitor

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4

Organism class: human
UniProt ID: P22748 Link_out
Gene: CA4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Epub 2008 Dec 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 26, 2010 13:31

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.