西氯他宁(Cicletanine) - 药物靶点：α-adrenergic receptor x β-adrenoceptors_在研适应症：高血压_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Cicletanine (USAN/INN)、cycletanide

+ [5]

靶点

α-adrenergic receptor x β-adrenoceptors

作用机制

α-adrenergic receptor激动剂(α-肾上腺素能受体家族激动剂)、β-adrenoceptors激动剂(β-肾上腺素能受体家族激动剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构

Gilead Sciences, Inc.Navitas Pharma, Inc.

最高研发阶段批准上市

首次获批日期

日本 (1988-01-01),

高血压

最高研发阶段(中国)-

特殊审评孤儿药 (美国)

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结构

分子式C14H12ClNO2

InChIKeyCVKNDPRBJVBDSS-UHFFFAOYSA-N

CAS号89943-82-8

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关联

2

项与西氯他宁相关的临床试验

NCT02709031 / Not yet recruiting临床1/2期

Cicletanine in Hypertension With Diabetes: Added Magnesium Preserves Potassium and Sodium

Cicletanine, which has been approved and launched for hypertension in France and Germany, has promise beyond hypertension in critically-unmet needs such as diabetes. It is evident from in vitro, animal and human studies that cicletanine's optimal dose in diabetes and other challenging, critically-unmet needs is likely to be higher than that for hypertension. Cicletanine's maximum tolerated dosage is not known, but the drug's dose-limiting effects are documented to be potassium loss and sodium loss from thiazide-type activity (one of the therapeutic mechanisms the drug is known to have); such thiazide-type losses are known to be reversed safely by magnesium. This trial explores the ability of magnesium to enhance cicletanine safety at higher doses in a trial involving patients with hypertension complicated by diabetes.

开始日期2022-06-01

申办/合作机构

Navitas Pharma, Inc.

[+1]

NCT00832507 / Terminated临床2期

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter, Dose-ranging Study of Cicletanine in Subjects With Pulmonary Arterial Hypertension

This Phase 2, randomized, double-blind, placebo-controlled, multicenter, dose-ranging study will compare the efficacy, safety, and tolerability of cicletanine hydrochloride (HCl) to placebo in subjects with PAH. Study drug will be administered alone, or on the background of stable PAH therapy. The study will consist of 3 periods: a screening period, a 12-week placebo-controlled treatment period, and a long-term, blinded extension period.

开始日期2009-01-01

申办/合作机构

Gilead Sciences, Inc.

100 项与西氯他宁相关的临床结果

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100 项与西氯他宁相关的转化医学

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100 项与西氯他宁相关的专利（医药）

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193

项与西氯他宁相关的文献（医药）

2016-09-01·Kidney Research and Clinical Practice3区 · 医学

Cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients

3区 · 医学

ArticleOA

作者: Choi, Eun Young ; Choi, Jong-Wook ; Kang, Chong Myung ; Ro, Youngouk ; Kim, Gheun-Ho

BACKGROUNDCicletanine is an antihypertensive agent with vasorelaxant and diuretic properties. It has been widely used in European countries; however, cicletanine-associated electrolyte disturbances have yet to be defined. We investigated cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients.METHODSData from a total of 68 kidney transplant recipients who were treated for hypertension with cicletanine were retrospectively analyzed. Cicletanine-induced hyponatremia and hypokalemia were defined as serum sodium < 135 mmol/L and potassium < 3.5 mmol/L, respectively, after the use of cicletanine.RESULTSThe average patient age was 50 (±11) years, and 44 (65%) were male. The daily dose of cicletanine was 171 ± 46 mg, and the duration of drug use was 215 ± 514 days. Hyponatremia occurred in 11 patients (16.2%), and hypokalemia occurred in 8 patients (11.8%). Three patients (4.4%) had hyponatremia and hypokalemia simultaneously. The duration of cicletanine administration was significantly longer in patients with hyponatremia than in those without hyponatremia (943 ± 958 vs. 74 ± 166 days, P < 0.05). The occurrence of hypokalemia was not affected by either daily dose or duration of drug use. Among 11 patients with hyponatremia, 10 were corrected within 2 weeks after withdrawal of the drug and 1 was spontaneously corrected. Among 8 cases of hypokalemia, 7 were corrected after withdrawal of the drug and 1 was spontaneously corrected.CONCLUSIONWe demonstrate that cicletanine may induce hyponatremia or hypokalemia in kidney transplant patients. Hyponatremia is more frequently associated with cicletanine than hypokalemia, and extended use of cicletanine may increase the risk of hyponatremia.

2013-07-15·American Journal of Physiology-Gastrointestinal and Liver Physiology3区 · 医学

Cicletanine stimulates eNOS phosphorylation and NO production via Akt and MAP kinase/Erk signaling in sinusoidal endothelial cells

3区 · 医学

Article

作者: Liu, Songling ; Rockey, Don C.

The function of the endothelial isoform of nitric oxide synthase (eNOS) and production of nitric oxide (NO) is altered in a number of disease states. Pharmacological approaches to enhancing NO synthesis and thus perhaps endothelial function could have substantial benefits in patients. We analyzed the effect of cicletanine, a synthetic pyridine with potent vasodilatory characteristics, on eNOS function and NO production in normal (liver) and injured rat sinusoidal endothelial cells, and we studied the effect of cicletanine-induced NO on stellate cell contraction and portal pressure in an in vivo model of liver injury. Sinusoidal endothelial cells were isolated from normal and injured rat livers. After exposure to cicletanine, eNOS phosphorylation, NO synthesis, and the signaling pathway regulating eNOS activation were measured. Cicletanine led to an increase in eNOS (Ser1177) phosphorylation, cytochrome c reductase activity, l-arginine conversion to l-citrulline, as well as NO production. The mechanism of the effect of cicletanine appeared to be via the protein kinase B (Akt) and MAP kinase/Erk signaling pathways. Additionally, cicletanine improved NO synthesis in injured sinusoidal endothelial cells. NO production induced by cicletanine in sinusoidal endothelial cells increased protein kinase G (PKG) activity as well as relaxation of stellate cells. Finally, administration of cicletanine to mice with portal hypertension induced by bile duct ligation led to reduction of portal pressure. The data indicate that cicletanine might improve eNOS activity in injured sinusoidal endothelial cells and likely activates hepatic stellate cell NO/PKG signaling. It raises the possibility that cicletanine could improve intrahepatic vascular function in portal hypertensive patients.

2012-08-01·Journal of Cardiovascular Pharmacology4区 · 医学

Beneficial Cardiac Effects of Cicletanine in Conscious Rabbits With Metabolic Syndrome

4区 · 医学

Article

作者: Réka Sári ; Di Yin ; László Drimba ; József Németh ; Barna Peitl ; Csaba Hegedüs ; Zoltán Szilvássy

BACKGROUND AND PURPOSEHigh-fat diet and consequent metabolic syndrome (MS) can lead to elevated risk for cardiac arrhythmias. This preclinical study was to investigate if cicletanine (CIC) could produce cardioprotective effects in conscious rabbits exhibiting the main symptoms of MS.METHODSNZW rabbits that had undergone an 8-week-long cholesterol-enriched diet (1.5%) were instrumented with a pacemaker electrode and randomly assigned into 3 groups according to the oral treatment of either CIC (50 mg·kg) or sotalol (25 mg·kg) and their placebo b.i.d. over 5 days. Study groups were subjected to either "arrhythmia challenge" by programmed electrical stimulation in the "Arrhythmogenesis" study (N = 54) or global myocardial ischemia by rapid pacing in the "Ventricular Overdrive Pacing-induced Myocardial Ischemia" study (N = 18). The antiarrhythmic effect was evaluated by the establishment of the incidence of programmed electrical stimulation-induced arrhythmias. Proarrhythmia indicators (eg, QTc, Tpeak-Tend) were also measured to assess the cardiac safety profile of CIC. To evaluate the background of antiarrhythmic effect, cardiac cyclic nucleotide (cyclic 3',5'-guanosine monophosphate [cGMP], cyclic 3',5'-adenosine monophosphate [cAMP]) and nitric oxide content were determined. The antiischemic effect was characterized by change of intracavital ST segment.RESULTSCicletanine treatment significantly decreased the incidence of ventricular arrhythmias, increased cardiac cGMP and nitric oxide content and reduced cardiac cAMP level. Cicletanine did not modify significantly QTc and Tpeak-Tend interval. The ST-segment change in response to rapid pacing was reduced significantly by CIC. (P < 0.05).CONCLUSIONSCicletanine exerts beneficial cardiac effects in rabbits with symptoms of MS, which may be of influence with regard to the clinical application of the drug.

100 项与西氯他宁相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D03487	西氯他宁	C03BX03	DB12766

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
高血压	日本	Ipsen SA	1988-01-01

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
肺动脉高压	临床前	德国	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	墨西哥	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	澳大利亚	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	美国	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	西班牙	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	奥地利	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	比利时	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	以色列	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	英国	Gilead Sciences, Inc.	2009-01-01
肺动脉高压	临床前	加拿大	Gilead Sciences, Inc.	2009-01-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ERS2012	临床2期	肺动脉高压	162	Cicletanine 150 mg qd	(獵淵繭積夢夢鬱餘範選) = 獵獵構網鹽餘積網積獵鑰齋憲鑰觸鑰淵繭艱鏇 (網築鑰網憲壓築簾衊鏇, -8.0 ~ 24.0)	不佳	2012-09-01
ERS2012	临床2期	肺动脉高压	162	Cicletanine 150 mg bid	(獵淵繭積夢夢鬱餘範選) = 築淵膚鹽窪艱艱築鹽簾鑰齋憲鑰觸鑰淵繭艱鏇 (網築鑰網憲壓築簾衊鏇, -8.0 ~ 24.0)	不佳	2012-09-01
FP321 (ERA2012)	N/A	低钾血症 \| 低钠血症	68	Cicletanine	膚範鬱願鹽繭齋糧齋膚(遞糧積網衊淵膚窪網選) = Cicletanine-induced hypokalemia occurred in 8 (11.8%) 鏇範淵選選獵鏇築膚糧 (蓋網鑰憲窪簾鑰遞壓淵 ) 更多	积极	2012-05-01