CICLETANINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C14H12ClNO2
Molecular Weight	261.704
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(O)C2=C(C=N1)C(OC2)C3=CC=C(Cl)C=C3

InChI

InChIKey=CVKNDPRBJVBDSS-UHFFFAOYSA-N

InChI=1S/C14H12ClNO2/c1-8-13(17)12-7-18-14(11(12)6-16-8)9-2-4-10(15)5-3-9/h2-6,14,17H,7H2,1H3

HIDE SMILES / InChI

Description
Sources: https://www.ipsen.com/websites/IPSENCOM-PROD/wp-content/uploads/2016/06/29140317/Ipsen_AR_2005_EN.pdf | https://www.ncbi.nlm.nih.gov/pubmed/10428010

Cicletanine is a diuretic, developed by Ipsen for the treatment of hypertension. The drug was marketed in France by Recordati under the name Tenstaten. The mechanism(s) by which cicletanine exerts its biological effects has not been definitely established. The salidiuretic activity appears to be the result of an action of the sulfoconjugated metabolite of cicletanine, which inhibits the apical Na+-dependent Cl-/HCO3- anion exchanger in the distal convoluted tubule. The mechanism of the vasodilating effect of cicletanine may include stimulation of vascular prostaglandin synthesis, inhibition of the low Km cyclic GMP phosphodiesterases, and blockade of Ca2+ channels either directly or indirectly. The drug has also been shown to interact with other proteins, including alpha-adrenergic, vascular histamine, and muscarinic receptors.

CNS Activity

Originator

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.has-sante.fr/portail/upload/docs/application/pdf/ct010354.pdf	Primary		Approved 8583	TENSTATEN Approved Use Hypertension. Launch Date 1986

C_max

Value	Dose	Analyte	Population
20 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
14 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
115 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
81 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
109 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
7.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
12.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
31 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/ \| https://link.springer.com/chapter/10.1007/978-1-4613-2067-8_27	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CICLETANINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
7% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3358898/			CICLETANINE plasma	Homo sapiens

Doses

Dose	Population	Adverse events
100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3323257/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/3323257/	Sources: https://pubmed.ncbi.nlm.nih.gov/3323257/
150 mg single, oral Studied dose Dose: 150 mg Route: oral Route: single Dose: 150 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22278145/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/22278145/	Sources: https://pubmed.ncbi.nlm.nih.gov/22278145/

PubMed

Title	Date	PubMed
Emerging therapies for the treatment of pulmonary hypertension.	2010-03	20216170
Blood pressure lowering efficacy of loop diuretics for primary hypertension.	2009-10-07	19821314
Update on pulmonary hypertension complicating chronic obstructive pulmonary disease.	2009	19802350
Cicletanine for the treatment of pulmonary arterial hypertension.	2008-10-27	18955648
Updated meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure.	2007	17914893
Insulin sensitization induced by oral cicletanine in conscious rabbits.	2006-09	16955283
Protective effect of cicletanine on renal function in diabetic spontaneously hypertensive rats.	2004-11	15672472
Myocardial PKC beta2 and the sensitivity of Na/K-ATPase to marinobufagenin are reduced by cicletanine in Dahl hypertension.	2003-03	12623951
Diuretics in the therapy of hypertension.	2002-03	11986901
Effect of cicletanine on the nitric oxide pathway in human umbilical vein endothelial cells.	2001-08	11483866
Cicletanine stimulates nitric oxide release and scavenges superoxide in endothelial cells.	2001-06	11392468
Nitric oxide, peroxynitrite and cGMP in atherosclerosis-induced hypertension in rabbits: beneficial effects of cicletanine.	2001-02-15	11173993
Renal-protective effect of nondepressor dose of cicletanine in diabetic rats with hypertension.	2000-03	10777035
[Comparison of the effects of cicletanine and captopril on kidney and heart lesions in spontaneously hypertensive rats (SHR-SP)].	1989-11	2514660

Patents

Sample Use Guides

In Vivo Use Guide

The treatment is initiated with 50 mg/day, but the effective dosage is usually 100 mg/day.

Route of Administration: Oral

In Vitro Use Guide

The effect of cicletanine on active tension was investigated in rat thoracic aortas. At concentrations from 3*10(-5) M to 3*10(-4) M the drug caused a concentration-related relaxation of noradrenaline, serotonin and prostaglandin F2alpha-induced contractions.

Name

Type

Language

(±)-BN-1270

Preferred Name

English

CICLETANINE

Official Name

English

CICLETANINE [USAN]

Common Name

English

CICLETANINE [MI]

Common Name

English

cicletanine [INN]

Common Name

English

Cicletanine [WHO-DD]

Common Name

English

CICLETANINE [MART.]

Common Name

English

WIN 90,000

Code

English

BN-1270

Code

English

CYCLETANIDE

Common Name

English

WIN-90000

Code

English

Classification Tree Code System Code

WHO-VATC

QC03BX03