Identification

Name
Cyclothiazide
Accession Number
DB00606  (APRD00895, EXPT01082)
Type
Small Molecule
Groups
Approved
Description

As a diuretic, cyclothiazide 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 cyclothiazide 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 cyclothiazide 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. Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.

Structure
Thumb
Synonyms
  • 6-chloro-3-(2-Norbornen-5-yl)-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide
  • 6-chloro-3,4-dihydro-3-(2-Norbornen-5-yl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
  • 6-chloro-3,4-dihydro-3-(2-Norbornen-5-yl)-7-sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide
  • 6-chloro-3,4-dihydro-3-(5-Norbornen-2-yl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide
  • Ciclotiazida
  • Ciclotiazide
  • Cyclothiazide
  • Cyclothiazidum
International/Other Brands
Acquirel / Anhydron (Lilly) / Doburil (Boehringer Ingelheim) / Fluidil / Renazide / Tensodiural / Valmiran (Boehringer Ingelheim)
Categories
UNII
P71U09G5BW
CAS number
2259-96-3
Weight
Average: 389.878
Monoisotopic: 389.027075102
Chemical Formula
C14H16ClN3O4S2
InChI Key
BOCUKUHCLICSIY-UHFFFAOYSA-N
InChI
InChI=1S/C14H16ClN3O4S2/c15-10-5-11-13(6-12(10)23(16,19)20)24(21,22)18-14(17-11)9-4-7-1-2-8(9)3-7/h1-2,5-9,14,17-18H,3-4H2,(H2,16,19,20)
IUPAC Name
3-{bicyclo[2.2.1]hept-5-en-2-yl}-6-chloro-1,1-dioxo-3,4-dihydro-2H-1λ⁶,2,4-benzothiadiazine-7-sulfonamide
SMILES
NS(=O)(=O)C1=C(Cl)C=C2NC(NS(=O)(=O)C2=C1)C1CC2CC1C=C2

Pharmacology

Indication

Cyclothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. It is also indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.

Structured Indications
Not Available
Pharmacodynamics

Like other thiazides, cyclothiazide promotes water loss from the body (diuretics). It inhibits Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue. Cyclothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy. Cyclothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.

Mechanism of action

Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.

TargetActionsOrganism
ASodium/potassium-transporting ATPase subunit gamma
inhibitor
Human
UCarbonic anhydrase 1
inhibitor
Human
UCarbonic anhydrase 2
inhibitor
Human
UCarbonic anhydrase 4
inhibitor
Human
USecreted frizzled-related protein 4
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

Oral LD50 in mouse is > 10000 mg/kg, and > 4000 mg/kg in rat. Signs of overdose include those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered hypokalemia may accentuate cardiac arrhythmias.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Cyclothiazide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Cyclothiazide.Experimental
AcebutololCyclothiazide may increase the hypotensive activities of Acebutolol.Approved
AlfentanilThe risk or severity of adverse effects can be increased when Alfentanil is combined with Cyclothiazide.Approved, Illicit
AlfuzosinAlfuzosin may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
AliskirenCyclothiazide may increase the hypotensive activities of Aliskiren.Approved, Investigational
AlphacetylmethadolThe risk or severity of adverse effects can be increased when Alphacetylmethadol is combined with Cyclothiazide.Experimental, Illicit
AlphaprodineThe risk or severity of adverse effects can be increased when Alphaprodine is combined with Cyclothiazide.Illicit
AlprenololCyclothiazide may increase the hypotensive activities of Alprenolol.Approved, Withdrawn
AmbrisentanCyclothiazide may increase the hypotensive activities of Ambrisentan.Approved, Investigational
AmifostineCyclothiazide may increase the hypotensive activities of Amifostine.Approved, Investigational
AmlodipineAmlodipine may increase the hypotensive activities of Cyclothiazide.Approved
AmphetamineAmphetamine may increase the hypotensive activities of Cyclothiazide.Approved, Illicit
AtenololAtenolol may increase the hypotensive activities of Cyclothiazide.Approved
AvanafilAvanafil may increase the antihypertensive activities of Cyclothiazide.Approved
BenazeprilBenazepril may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
BendroflumethiazideBendroflumethiazide may increase the hypotensive activities of Cyclothiazide.Approved
BenmoxinBenmoxin may increase the hypotensive activities of Cyclothiazide.Withdrawn
BepridilCyclothiazide may increase the hypotensive activities of Bepridil.Approved, Withdrawn
BetaxololBetaxolol may increase the hypotensive activities of Cyclothiazide.Approved
BethanidineBethanidine may increase the hypotensive activities of Cyclothiazide.Approved
BezitramideThe risk or severity of adverse effects can be increased when Bezitramide is combined with Cyclothiazide.Experimental, Illicit, Withdrawn
BietaserpineBietaserpine may increase the hypotensive activities of Cyclothiazide.Experimental
BimatoprostCyclothiazide may increase the hypotensive activities of Bimatoprost.Approved, Investigational
BisoprololCyclothiazide may increase the hypotensive activities of Bisoprolol.Approved
BosentanBosentan may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
BQ-123Cyclothiazide may increase the hypotensive activities of BQ-123.Investigational
BretyliumCyclothiazide may increase the hypotensive activities of Bretylium.Approved
BrimonidineBrimonidine may increase the antihypertensive activities of Cyclothiazide.Approved
BrofaromineBrofaromine may increase the hypotensive activities of Cyclothiazide.Experimental
BupranololCyclothiazide may increase the hypotensive activities of Bupranolol.Approved
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Cyclothiazide.Approved, Illicit, Investigational, Vet Approved
ButorphanolThe risk or severity of adverse effects can be increased when Butorphanol is combined with Cyclothiazide.Approved, Illicit, Vet Approved
CadralazineCadralazine may increase the hypotensive activities of Cyclothiazide.Experimental
CafedrineCyclothiazide may increase the hypotensive activities of Cafedrine.Investigational
CandesartanCyclothiazide may increase the hypotensive activities of Candesartan.Experimental
Candesartan cilexetilCyclothiazide may increase the hypotensive activities of Candesartan cilexetil.Approved
CandoxatrilCyclothiazide may increase the hypotensive activities of Candoxatril.Experimental
CaptoprilCyclothiazide may increase the hypotensive activities of Captopril.Approved
CarfentanilThe risk or severity of adverse effects can be increased when Carfentanil is combined with Cyclothiazide.Illicit, Investigational, Vet Approved
CaroxazoneCaroxazone may increase the hypotensive activities of Cyclothiazide.Withdrawn
CarteololCarteolol may increase the hypotensive activities of Cyclothiazide.Approved
CarvedilolCyclothiazide may increase the hypotensive activities of Carvedilol.Approved, Investigational
CeliprololCyclothiazide may increase the hypotensive activities of Celiprolol.Approved, Investigational
ChlorothiazideCyclothiazide may increase the hypotensive activities of Chlorothiazide.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypotensive activities of Cyclothiazide.Approved
CicletanineCyclothiazide may increase the hypotensive activities of Cicletanine.Investigational
CilazaprilCyclothiazide may increase the hypotensive activities of Cilazapril.Approved
ClonidineClonidine may increase the hypotensive activities of Cyclothiazide.Approved
CloranololCyclothiazide may increase the hypotensive activities of Cloranolol.Experimental
CodeineThe risk or severity of adverse effects can be increased when Codeine is combined with Cyclothiazide.Approved, Illicit
CryptenamineCyclothiazide may increase the hypotensive activities of Cryptenamine.Approved
CyclopenthiazideCyclothiazide may increase the hypotensive activities of Cyclopenthiazide.Experimental
DebrisoquinDebrisoquin may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
DelaprilCyclothiazide may increase the hypotensive activities of Delapril.Experimental
DeserpidineCyclothiazide may increase the hypotensive activities of Deserpidine.Approved
DexketoprofenThe risk or severity of adverse effects can be increased when Dexketoprofen is combined with Cyclothiazide.Approved, Investigational
DextromoramideThe risk or severity of adverse effects can be increased when Dextromoramide is combined with Cyclothiazide.Experimental, Illicit
DextropropoxypheneThe risk or severity of adverse effects can be increased when Dextropropoxyphene is combined with Cyclothiazide.Approved, Illicit, Investigational, Withdrawn
DezocineThe risk or severity of adverse effects can be increased when Dezocine is combined with Cyclothiazide.Approved, Investigational
DiazoxideDiazoxide may increase the hypotensive activities of Cyclothiazide.Approved
diethylnorspermineCyclothiazide may increase the hypotensive activities of diethylnorspermine.Investigational
DihydralazineDihydralazine may increase the hypotensive activities of Cyclothiazide.Investigational
DihydrocodeineThe risk or severity of adverse effects can be increased when Dihydrocodeine is combined with Cyclothiazide.Approved, Illicit
DihydroetorphineThe risk or severity of adverse effects can be increased when Dihydroetorphine is combined with Cyclothiazide.Experimental, Illicit
DihydromorphineThe risk or severity of adverse effects can be increased when Dihydromorphine is combined with Cyclothiazide.Experimental, Illicit
DiltiazemDiltiazem may increase the hypotensive activities of Cyclothiazide.Approved
DiphenoxylateThe risk or severity of adverse effects can be increased when Diphenoxylate is combined with Cyclothiazide.Approved, Illicit
DorzolamideCyclothiazide may increase the hypotensive activities of Dorzolamide.Approved
DoxazosinDoxazosin may increase the hypotensive activities of Cyclothiazide.Approved
DPDPEThe risk or severity of adverse effects can be increased when DPDPE is combined with Cyclothiazide.Experimental
EfonidipineCyclothiazide may increase the hypotensive activities of Efonidipine.Approved, Investigational
EnalaprilEnalapril may increase the hypotensive activities of Cyclothiazide.Approved, Vet Approved
EnalaprilatCyclothiazide may increase the hypotensive activities of Enalaprilat.Approved
EndralazineEndralazine may increase the hypotensive activities of Cyclothiazide.Experimental
EpanololCyclothiazide may increase the hypotensive activities of Epanolol.Experimental
EpoprostenolCyclothiazide may increase the hypotensive activities of Epoprostenol.Approved
EprosartanCyclothiazide may increase the hypotensive activities of Eprosartan.Approved
EthylmorphineThe risk or severity of adverse effects can be increased when Ethylmorphine is combined with Cyclothiazide.Approved, Illicit
EtorphineThe risk or severity of adverse effects can be increased when Etorphine is combined with Cyclothiazide.Illicit, Vet Approved
FelodipineCyclothiazide may increase the hypotensive activities of Felodipine.Approved, Investigational
FenoldopamCyclothiazide may increase the hypotensive activities of Fenoldopam.Approved
FentanylThe risk or severity of adverse effects can be increased when Fentanyl is combined with Cyclothiazide.Approved, Illicit, Investigational, Vet Approved
Ferulic acidCyclothiazide may increase the hypotensive activities of Ferulic acid.Experimental
FosinoprilFosinopril may increase the hypotensive activities of Cyclothiazide.Approved
FurazolidoneFurazolidone may increase the hypotensive activities of Cyclothiazide.Approved, Investigational, Vet Approved
GuanabenzCyclothiazide may increase the hypotensive activities of Guanabenz.Approved, Investigational
GuanadrelGuanadrel may increase the hypotensive activities of Cyclothiazide.Approved
GuanazodineCyclothiazide may increase the hypotensive activities of Guanazodine.Experimental
GuanethidineCyclothiazide may increase the hypotensive activities of Guanethidine.Approved
GuanfacineGuanfacine may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
GuanoclorCyclothiazide may increase the hypotensive activities of Guanoclor.Experimental
GuanoxabenzCyclothiazide may increase the hypotensive activities of Guanoxabenz.Experimental
GuanoxanCyclothiazide may increase the hypotensive activities of Guanoxan.Experimental
HarmalineHarmaline may increase the hypotensive activities of Cyclothiazide.Experimental
HeroinThe risk or severity of adverse effects can be increased when Heroin is combined with Cyclothiazide.Approved, Illicit, Investigational
HexamethoniumCyclothiazide may increase the hypotensive activities of Hexamethonium.Experimental
HydracarbazineHydracarbazine may increase the hypotensive activities of Cyclothiazide.Experimental
HydralazineHydralazine may increase the hypotensive activities of Cyclothiazide.Approved
HydrochlorothiazideCyclothiazide may increase the hypotensive activities of Hydrochlorothiazide.Approved, Vet Approved
HydrocodoneThe risk or severity of adverse effects can be increased when Hydrocodone is combined with Cyclothiazide.Approved, Illicit
HydroflumethiazideCyclothiazide may increase the hypotensive activities of Hydroflumethiazide.Approved, Investigational
HydromorphoneThe risk or severity of adverse effects can be increased when Hydromorphone is combined with Cyclothiazide.Approved, Illicit
IloprostIloprost may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
ImidaprilCyclothiazide may increase the hypotensive activities of Imidapril.Investigational
IndapamideCyclothiazide may increase the hypotensive activities of Indapamide.Approved
IndenololCyclothiazide may increase the hypotensive activities of Indenolol.Withdrawn
IndoraminIndoramin may increase the hypotensive activities of Cyclothiazide.Withdrawn
IproclozideIproclozide may increase the hypotensive activities of Cyclothiazide.Withdrawn
IproniazidIproniazid may increase the hypotensive activities of Cyclothiazide.Withdrawn
IrbesartanCyclothiazide may increase the hypotensive activities of Irbesartan.Approved, Investigational
IsocarboxazidIsocarboxazid may increase the hypotensive activities of Cyclothiazide.Approved
IsradipineIsradipine may increase the hypotensive activities of Cyclothiazide.Approved
KetanserinKetanserin may increase the hypotensive activities of Cyclothiazide.Investigational
KetobemidoneThe risk or severity of adverse effects can be increased when Ketobemidone is combined with Cyclothiazide.Approved, Investigational
LabetalolLabetalol may increase the hypotensive activities of Cyclothiazide.Approved
LacidipineCyclothiazide may increase the hypotensive activities of Lacidipine.Approved, Investigational
LatanoprostCyclothiazide may increase the hypotensive activities of Latanoprost.Approved, Investigational
LercanidipineLercanidipine may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
Levomethadyl AcetateThe risk or severity of adverse effects can be increased when Levomethadyl Acetate is combined with Cyclothiazide.Approved, Investigational
LevorphanolThe risk or severity of adverse effects can be increased when Levorphanol is combined with Cyclothiazide.Approved
LinsidomineCyclothiazide may increase the hypotensive activities of Linsidomine.Experimental
LisinoprilCyclothiazide may increase the hypotensive activities of Lisinopril.Approved, Investigational
LofentanilThe risk or severity of adverse effects can be increased when Lofentanil is combined with Cyclothiazide.Illicit
LofexidineCyclothiazide may increase the hypotensive activities of Lofexidine.Approved, Investigational
LosartanCyclothiazide may increase the hypotensive activities of Losartan.Approved
MacitentanCyclothiazide may increase the hypotensive activities of Macitentan.Approved
ManidipineCyclothiazide may increase the hypotensive activities of Manidipine.Approved, Investigational
MebanazineMebanazine may increase the hypotensive activities of Cyclothiazide.Withdrawn
MecamylamineThe risk or severity of adverse effects can be increased when Cyclothiazide is combined with Mecamylamine.Approved
MeptazinolThe risk or severity of adverse effects can be increased when Meptazinol is combined with Cyclothiazide.Experimental
MethadoneThe risk or severity of adverse effects can be increased when Methadone is combined with Cyclothiazide.Approved
Methadyl AcetateThe risk or severity of adverse effects can be increased when Methadyl Acetate is combined with Cyclothiazide.Approved, Illicit
MethoserpidineCyclothiazide may increase the hypotensive activities of Methoserpidine.Experimental
MethyldopaCyclothiazide may increase the hypotensive activities of Methyldopa.Approved
Methylene blueMethylene blue may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
MethylphenidateMethylphenidate may decrease the antihypertensive activities of Cyclothiazide.Approved, Investigational
MetipranololCyclothiazide may increase the hypotensive activities of Metipranolol.Approved
MetolazoneMetolazone may increase the hypotensive activities of Cyclothiazide.Approved
MetoprololMetoprolol may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
MetyrosineCyclothiazide may increase the hypotensive activities of Metyrosine.Approved
MibefradilCyclothiazide may increase the hypotensive activities of Mibefradil.Investigational, Withdrawn
MinaprineMinaprine may increase the hypotensive activities of Cyclothiazide.Approved
MinoxidilMinoxidil may increase the hypotensive activities of Cyclothiazide.Approved
MirodenafilMirodenafil may increase the antihypertensive activities of Cyclothiazide.Investigational
MoclobemideMoclobemide may increase the hypotensive activities of Cyclothiazide.Approved
MoexiprilCyclothiazide may increase the hypotensive activities of Moexipril.Approved
MolsidomineMolsidomine may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
MorphineThe risk or severity of adverse effects can be increased when Morphine is combined with Cyclothiazide.Approved, Investigational
MoxonidineMoxonidine may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
MuzolimineCyclothiazide may increase the hypotensive activities of Muzolimine.Experimental
NadololCyclothiazide may increase the hypotensive activities of Nadolol.Approved
NaftopidilCyclothiazide may increase the hypotensive activities of Naftopidil.Investigational
NalbuphineThe risk or severity of adverse effects can be increased when Nalbuphine is combined with Cyclothiazide.Approved
NebivololCyclothiazide may increase the hypotensive activities of Nebivolol.Approved, Investigational
NialamideNialamide may increase the hypotensive activities of Cyclothiazide.Withdrawn
NicardipineCyclothiazide may increase the hypotensive activities of Nicardipine.Approved
NicomorphineThe risk or severity of adverse effects can be increased when Nicomorphine is combined with Cyclothiazide.Experimental
NicorandilCyclothiazide may increase the hypotensive activities of Nicorandil.Approved, Investigational
NiguldipineCyclothiazide may increase the hypotensive activities of Niguldipine.Experimental
NilvadipineCyclothiazide may increase the hypotensive activities of Nilvadipine.Approved, Investigational
NimodipineNimodipine may increase the hypotensive activities of Cyclothiazide.Approved
NisoldipineNisoldipine may increase the hypotensive activities of Cyclothiazide.Approved
NitrendipineCyclothiazide may increase the hypotensive activities of Nitrendipine.Approved, Investigational
NitroprussideNitroprusside may increase the hypotensive activities of Cyclothiazide.Approved
NormethadoneThe risk or severity of adverse effects can be increased when Normethadone is combined with Cyclothiazide.Approved, Illicit
ObinutuzumabCyclothiazide may increase the hypotensive activities of Obinutuzumab.Approved
OctamoxinOctamoxin may increase the hypotensive activities of Cyclothiazide.Withdrawn
OlmesartanOlmesartan may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
OmapatrilatCyclothiazide may increase the hypotensive activities of Omapatrilat.Investigational
OpiumThe risk or severity of adverse effects can be increased when Opium is combined with Cyclothiazide.Approved, Illicit
OxprenololCyclothiazide may increase the hypotensive activities of Oxprenolol.Approved
OxycodoneThe risk or severity of adverse effects can be increased when Oxycodone is combined with Cyclothiazide.Approved, Illicit, Investigational
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Cyclothiazide.Approved, Investigational, Vet Approved
PargylinePargyline may increase the hypotensive activities of Cyclothiazide.Approved
PenbutololCyclothiazide may increase the hypotensive activities of Penbutolol.Approved, Investigational
PentazocineThe risk or severity of adverse effects can be increased when Pentazocine is combined with Cyclothiazide.Approved, Vet Approved
PentoliniumCyclothiazide may increase the hypotensive activities of Pentolinium.Approved
PentoxifyllinePentoxifylline may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
PerindoprilCyclothiazide may increase the hypotensive activities of Perindopril.Approved
PethidineThe risk or severity of adverse effects can be increased when Pethidine is combined with Cyclothiazide.Approved
PhenazocineThe risk or severity of adverse effects can be increased when Phenazocine is combined with Cyclothiazide.Experimental
PhenelzinePhenelzine may increase the hypotensive activities of Cyclothiazide.Approved
PheniprazinePheniprazine may increase the hypotensive activities of Cyclothiazide.Withdrawn
PhenoperidineThe risk or severity of adverse effects can be increased when Phenoperidine is combined with Cyclothiazide.Experimental
PhenoxybenzamineCyclothiazide may increase the hypotensive activities of Phenoxybenzamine.Approved
PhenoxypropazinePhenoxypropazine may increase the hypotensive activities of Cyclothiazide.Withdrawn
PhentolamineCyclothiazide may increase the hypotensive activities of Phentolamine.Approved
PinacidilPinacidil may increase the hypotensive activities of Cyclothiazide.Withdrawn
PindololCyclothiazide may increase the hypotensive activities of Pindolol.Approved
PiritramideThe risk or severity of adverse effects can be increased when Piritramide is combined with Cyclothiazide.Investigational
PirlindolePirlindole may increase the hypotensive activities of Cyclothiazide.Approved
PivhydrazinePivhydrazine may increase the hypotensive activities of Cyclothiazide.Withdrawn
Platelet Activating FactorCyclothiazide may increase the hypotensive activities of Platelet Activating Factor.Experimental
PolythiazideCyclothiazide may increase the hypotensive activities of Polythiazide.Approved
PrazosinPrazosin may increase the hypotensive activities of Cyclothiazide.Approved
ProcarbazineProcarbazine may increase the hypotensive activities of Cyclothiazide.Approved
PropranololPropranolol may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
QuinaprilCyclothiazide may increase the hypotensive activities of Quinapril.Approved, Investigational
QuinineQuinine may increase the hypotensive activities of Cyclothiazide.Approved
RamiprilRamipril may increase the hypotensive activities of Cyclothiazide.Approved
RasagilineRasagiline may increase the hypotensive activities of Cyclothiazide.Approved
RemifentanilThe risk or severity of adverse effects can be increased when Remifentanil is combined with Cyclothiazide.Approved
RemikirenRemikiren may increase the hypotensive activities of Cyclothiazide.Approved
RescinnamineCyclothiazide may increase the hypotensive activities of Rescinnamine.Approved
ReserpineReserpine may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
RilmenidineRilmenidine may increase the hypotensive activities of Cyclothiazide.Investigational
RiociguatCyclothiazide may increase the hypotensive activities of Riociguat.Approved
RituximabCyclothiazide may increase the hypotensive activities of Rituximab.Approved
SafrazineSafrazine may increase the hypotensive activities of Cyclothiazide.Withdrawn
SaprisartanCyclothiazide may increase the hypotensive activities of Saprisartan.Experimental
SelegilineSelegiline may increase the hypotensive activities of Cyclothiazide.Approved, Investigational, Vet Approved
SelexipagCyclothiazide may increase the hypotensive activities of Selexipag.Approved
SildenafilSildenafil may increase the antihypertensive activities of Cyclothiazide.Approved, Investigational
SitaxentanCyclothiazide may increase the hypotensive activities of Sitaxentan.Approved, Investigational, Withdrawn
Sodium phosphateCyclothiazide may increase the nephrotoxic activities of Sodium phosphate.Approved
SpiraprilCyclothiazide may increase the hypotensive activities of Spirapril.Approved
SufentanilThe risk or severity of adverse effects can be increased when Sufentanil is combined with Cyclothiazide.Approved, Investigational
TadalafilTadalafil may increase the antihypertensive activities of Cyclothiazide.Approved, Investigational
TalinololCyclothiazide may increase the hypotensive activities of Talinolol.Investigational
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Cyclothiazide.Approved
TelmisartanCyclothiazide may increase the hypotensive activities of Telmisartan.Approved, Investigational
TemocaprilCyclothiazide may increase the hypotensive activities of Temocapril.Experimental, Investigational
TerlipressinCyclothiazide may increase the hypotensive activities of Terlipressin.Approved, Investigational
TetrahydropalmatineCyclothiazide may increase the hypotensive activities of Tetrahydropalmatine.Investigational
TheodrenalineCyclothiazide may increase the hypotensive activities of Theodrenaline.Investigational
TiboloneCyclothiazide may increase the hypotensive activities of Tibolone.Approved, Investigational
TicrynafenCyclothiazide may increase the hypotensive activities of Ticrynafen.Withdrawn
TilidineThe risk or severity of adverse effects can be increased when Tilidine is combined with Cyclothiazide.Experimental
TimololTimolol may increase the hypotensive activities of Cyclothiazide.Approved
TolazolineCyclothiazide may increase the hypotensive activities of Tolazoline.Approved, Vet Approved
TolonidineCyclothiazide may increase the hypotensive activities of Tolonidine.Experimental
ToloxatoneToloxatone may increase the hypotensive activities of Cyclothiazide.Approved
TorasemideTorasemide may increase the hypotensive activities of Cyclothiazide.Approved
TramadolThe risk or severity of adverse effects can be increased when Tramadol is combined with Cyclothiazide.Approved, Investigational
TrandolaprilTrandolapril may increase the hypotensive activities of Cyclothiazide.Approved
Trans-2-PhenylcyclopropylamineTrans-2-Phenylcyclopropylamine may increase the hypotensive activities of Cyclothiazide.Experimental
TranylcypromineTranylcypromine may increase the hypotensive activities of Cyclothiazide.Approved
TravoprostTravoprost may increase the hypotensive activities of Cyclothiazide.Approved
TreprostinilTreprostinil may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
TrichlormethiazideCyclothiazide may increase the hypotensive activities of Trichlormethiazide.Approved, Vet Approved
TrimazosinTrimazosin may increase the hypotensive activities of Cyclothiazide.Experimental
TrimethaphanTrimethaphan may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
UdenafilUdenafil may increase the antihypertensive activities of Cyclothiazide.Approved, Investigational
UnoprostoneCyclothiazide may increase the hypotensive activities of Unoprostone.Approved
UrapidilUrapidil may increase the hypotensive activities of Cyclothiazide.Investigational
ValsartanValsartan may increase the hypotensive activities of Cyclothiazide.Approved, Investigational
VardenafilVardenafil may increase the antihypertensive activities of Cyclothiazide.Approved
VincamineCyclothiazide may increase the hypotensive activities of Vincamine.Experimental
VinpocetineCyclothiazide may increase the hypotensive activities of Vinpocetine.Investigational
XipamideCyclothiazide may increase the hypotensive activities of Xipamide.Experimental
XylometazolineCyclothiazide may increase the hypotensive activities of Xylometazoline.Approved
YohimbineYohimbine may decrease the antihypertensive activities of Cyclothiazide.Approved, Vet Approved
ZofenoprilCyclothiazide may increase the hypotensive activities of Zofenopril.Experimental
Food Interactions
Not Available

References

Synthesis Reference

Muller, E. and Hasspacher, K.; US. Patent 3,275,625; September 27,1966; assigned to Boehringer lngelheim GmbH, Germany.

General References
Not Available
External Links
Human Metabolome Database
HMDB14744
KEGG Drug
D01256
KEGG Compound
C12685
PubChem Compound
2910
PubChem Substance
46508269
ChemSpider
2807
BindingDB
50192229
ChEBI
31448
ChEMBL
CHEMBL61593
Therapeutic Targets Database
DAP000604
PharmGKB
PA449168
HET
CYZ
ATC Codes
C03AA09 — CyclothiazideC03AB09 — Cyclothiazide and potassiumG01AE10 — Combinations of sulfonamides
MSDS
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Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
  • Pharmacia and upjohn co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)229-230Muller, E. and Hasspacher, K.; US. Patent 3,275,625; September 27,1966; assigned to Boehringer lngelheim GmbH, Germany.
logP1.95YAMAZAKI,M ET AL. (1984)
Predicted Properties
PropertyValueSource
Water Solubility0.279 mg/mLALOGPS
logP1.32ALOGPS
logP0.94ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)9.06ChemAxon
pKa (Strongest Basic)-2.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.36 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity92.65 m3·mol-1ChemAxon
Polarizability37.1 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9936
Blood Brain Barrier-0.8102
Caco-2 permeable-0.7087
P-glycoprotein substrateNon-substrate0.6003
P-glycoprotein inhibitor INon-inhibitor0.8315
P-glycoprotein inhibitor IINon-inhibitor0.9504
Renal organic cation transporterNon-inhibitor0.894
CYP450 2C9 substrateNon-substrate0.6644
CYP450 2D6 substrateNon-substrate0.8212
CYP450 3A4 substrateNon-substrate0.6385
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorInhibitor0.7478
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.8015
CarcinogenicityNon-carcinogens0.813
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.9232 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9813
hERG inhibition (predictor II)Non-inhibitor0.8693
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
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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 / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives
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 / Aminosulfonyl compound / Sulfonyl
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
benzothiadiazine (CHEBI:31448)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transporter activity
Specific Function
May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
Gene Name
FXYD2
Uniprot ID
P54710
Uniprot Name
Sodium/potassium-transporting ATPase subunit gamma
Molecular Weight
7283.265 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. [PubMed:17139284]
  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:17016423]
Kind
Protein
Organism
Human
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. Rammes G, Zeilhofer HU, Collingridge GL, Parsons CG, Swandulla D: Expression of early hippocampal CA1 LTP does not lead to changes in AMPA-EPSC kinetics or sensitivity to cyclothiazide. Pflugers Arch. 1999 Jan;437(2):191-6. [PubMed:9929558]
  2. Rammes G, Swandulla D, Collingridge GL, Hartmann S, Parsons CG: Interactions of 2,3-benzodiazepines and cyclothiazide at AMPA receptors: patch clamp recordings in cultured neurones and area CA1 in hippocampal slices. Br J Pharmacol. 1996 Mar;117(6):1209-21. [PubMed:8882618]
  3. Fleck MW, Bahring R, Patneau DK, Mayer ML: AMPA receptor heterogeneity in rat hippocampal neurons revealed by differential sensitivity to cyclothiazide. J Neurophysiol. 1996 Jun;75(6):2322-33. [PubMed:8793745]
  4. Pirotte B, Podona T, Diouf O, de Tullio P, Lebrun P, Dupont L, Somers F, Delarge J, Morain P, Lestage P, Lepagnol J, Spedding M: 4H-1,2,4-Pyridothiadiazine 1,1-dioxides and 2,3-dihydro-4H-1,2, 4-pyridothiadiazine 1,1-dioxides chemically related to diazoxide and cyclothiazide as powerful positive allosteric modulators of (R/S)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid receptors: design, synthesis, pharmacology, and structure-activity relationships. J Med Chem. 1998 Jul 30;41(16):2946-59. [PubMed:9685234]
  5. Larson J, Le TT, Hall RA, Lynch G: Effects of cyclothiazide on synaptic responses in slices of adult and neonatal rat hippocampus. Neuroreport. 1994 Jan 12;5(4):389-92. [PubMed:8003661]
Kind
Protein
Organism
Human
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. Liljequist S, Cebers G, Kalda A: Effects of decahydroisoquinoline-3-carboxylic acid monohydrate, a novel AMPA receptor antagonist, on glutamate-induced CA2+ responses and neurotoxicity in rat cortical and cerebellar granule neurons. Biochem Pharmacol. 1995 Nov 27;50(11):1761-74. [PubMed:8615854]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927).
Specific Function
Wnt-protein binding
Gene Name
SFRP4
Uniprot ID
Q6FHJ7
Uniprot Name
Secreted frizzled-related protein 4
Molecular Weight
39826.305 Da
References
  1. Bukhari SA, Shamshari WA, Ur-Rahman M, Zia-Ul-Haq M, Jaafar HZ: Computer aided screening of secreted frizzled-related protein 4 (SFRP4): a potential control for diabetes mellitus. Molecules. 2014 Jul 11;19(7):10129-36. doi: 10.3390/molecules190710129. [PubMed:25019556]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. [PubMed:10991988]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:40