Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM4DMBT)

• Drug Name: Chlorthalidone Drug Info
• Synonyms: Chlorothalidone; Chlorphthalidolone; Chlorphthalidone; Chlortalidone; Chlortalidonum; Chlorthalidon; Clortalidona; Clortalidone; Famolin; Higroton; Hygroton; Igroton; Isoren; Natriuran; Oradil; Oxodolin; Oxodoline; Phthalamodine; Phthalamudine; Renon; Saluretin; Thalitone; Urolin; Zambesil; Clortalidone [DCIT]; Racemic chlorthalidone; G 33182; Chlortalidonum [INN-Latin]; Chlorthalidone (USP); Clortalidona [INN-Spanish]; G-33182; Hydro-Long; Hygroton (TN); Oksodolin (oxodolin); Thalitone (TN); Chlortalidone (JAN/INN); Chlorthalidone [USAN:INN:BAN]; (+-)-Chlorthalidone; (+-)-Hygroton; 1-Keto-3-(3'-sulfamyl-4'-chlorophenyl)-3-hydroxyisoindoline; 1-Oxo-3-(3-sulfamyl-4-chlorophenyl)-3-hydroxyisoindoline; 2-Chloro-5-(1-hydroxy-3-oxo-1-isoindolinyl)benzenesulfonamide; 2-Chloro-5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)benzenesulfonamide; 2-chloro-5-(1-hydroxy-3-oxo-2H-isoindol-1-yl)benzenesulfonamide; 2-chloro-5-(2,3-dihydro-1-hydroxy-3-oxo-1H-isoindol-1-yl)benzenesulfonamide; 3-(4'-Chloro-3'-sulfamoylphenyl)-3-hydroxyphthalimidine; 3-Hydroxy-3-(4-chloro-3-sulfamylphenyl)phthalimidine

Indication

Disease Entry	ICD 11	Status	REF
Edema	MG29	Approved	[1]
Hypertension	BA00-BA04	Approved	[1]
High blood pressure	BA00	Investigative	[2]

• Therapeutic Class: Antihypertensive Agents
• Cross-matching ID:
  PubChem CID: 2732
  ChEBI ID: CHEBI:3654
  CAS Number: CAS 77-36-1
  TTD Drug ID: DM4DMBT
  VARIDT Drug ID: DR01029
  ACDINA Drug ID: D00126

Molecule-Related Drug Atlas

Drug(s) Targeting Solute carrier family 12 member 1 (SLC12A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aldosterone	DM9S2JW	Hypertension	BA00-BA04	Approved	[5]
Potassium Chloride	DMMTAJC	Hypokalemia	5C77	Approved	[6]
Furosemide	DMMQ8ZG	Congestive heart failure	BD10	Approved	[7]
Bumetanide	DMRV7H0	Congestive heart failure	BD10	Approved	[8]
Ethacrynic acid	DM60QMR	Edema	MG29	Approved	[9]
Torasemide	DMXKJ6C	Congestive heart failure	BD10	Approved	[10]
Bendroflumethiazide	DM7EVLC	High blood pressure	BA00	Approved	[11]
Trichlormethiazide	DMHAQCO	Hypertension	BA00-BA04	Approved	[12]
Hydroflumethiazide	DMVPUQI	Congestive heart failure	BD10	Approved	[11]
Methyclothiazide	DMN7SDE	Edema	MG29	Approved	[11]

Drug(s) Affected By Renin (REN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ranitidine	DM0GUSX	Gastric ulcer	DA60	Approved	[13]
Acebutolol	DM0TI4U	Hypertension	BA00-BA04	Approved	[14]
Nitrendipine	DM21C09	Hypertension	BA00-BA04	Approved	[15]
Reboxetine	DM26PRD	Depression	6A70-6A7Z	Approved	[16]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[17]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[18]
Rhucin	DM3ADGP	Erectile dysfunction	HA01.1	Approved	[19]
Naloxone	DM3FXMA	Narcotic depression	6A7Z	Approved	[20]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[21]
Trandolapril	DM4L6EU	Chronic heart failure	BD1Z	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Solute carrier family 12 member 1 (SLC12A1)	TTS087L	S12A1_HUMAN	Blocker	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Renin (REN)	OT52GZR2	RENI_HUMAN	Gene/Protein Processing	[4]

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: 7147).
• [2] Chlorthalidone FDA Label
• [3] The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52.
• [4] Detection of low-renin hypertension; evaluation of out-patient renin-stimulating methods. Clin Sci Mol Med. 1975 Feb;48(2):91-6. doi: 10.1042/cs0480091.
• [5] Nongenomic effect of aldosterone on ion transport pathways of red blood cells. Cell Physiol Biochem. 2008;22(1-4):269-78.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Update of diuretics in the treatment of hypertension. Am J Ther. 2007 Mar-Apr;14(2):154-60.
• [8] Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37.
• [9] Na-K-Cl cotransport regulates intracellular volume and monolayer permeability of trabecular meshwork cells. Am J Physiol. 1995 Apr;268(4 Pt 1):C1067-74.
• [10] Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9.
• [11] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [12] Function and regulation of epithelial sodium transporters in the kidney of a salt-sensitive hypertensive rat model. J Hypertens. 2007 May;25(5):1065-72.
• [13] Effects of histamine H2-receptor blockade on the cardiovascular reflex response to lower-body negative pressure in man. Acta Physiol Scand. 1990 May;139(1):161-72. doi: 10.1111/j.1748-1716.1990.tb08909.x.
• [14] Addition of acebutolol to diuretics in hypertension. Clin Pharmacol Ther. 1981 Dec;30(6):739-44. doi: 10.1038/clpt.1981.232.
• [15] Relative potency of a beta-blocking and a calcium entry blocking agent as antihypertensive drugs in black patients. Eur J Clin Pharmacol. 1986;29(5):523-7. doi: 10.1007/BF00635887.
• [16] Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans. Hypertension. 2006 Jul;48(1):120-6. doi: 10.1161/01.HYP.0000225424.13138.5d. Epub 2006 May 22.
• [17] Effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis. Am J Med. 1990 Sep;89(3):313-21. doi: 10.1016/0002-9343(90)90344-d.
• [18] Effects of an angiotensin converting enzyme inhibitor, ramipril, on intracranial circulation in healthy volunteers. off. Br J Clin Pharmacol. 1992 Sep;34(3):224-30. doi: 10.1111/j.1365-2125.1992.tb04128.x.
• [19] Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites. Am J Physiol Renal Physiol. 2005 May;288(5):F1044-52. doi: 10.1152/ajprenal.00142.2004. Epub 2004 Dec 21.
• [20] beta-Endorphin and essential hypertension: importance of the clonidine-naloxone interaction. Acta Physiol Hung. 1985;65(2):217-26.
• [21] Hypokalemia from beta2-receptor stimulation by circulating epinephrine. N Engl J Med. 1983 Dec 8;309(23):1414-9. doi: 10.1056/NEJM198312083092303.
• [22] Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction. J Clin Pharm Ther. 2006 Apr;31(2):139-47. doi: 10.1111/j.1365-2710.2006.00606.x.