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Yu Guan, Daisuke Nakano, Zhang Yifan, Akira Nishiyama
OBJECTIVE: Previous studies have indicated the beneficial effects of N-type calcium channel blocker, cilnidipine, on protecting renal podocyte injury in metabolic syndrome model rats. In the present study, we examined the effects of cilnidipine (L/N-type calcium channel blocker) and nifedipine (L-type calcium channel blocker) on the glomerular filtration barrier damage in the doxorubicin-induced nephropathy mice model. DESIGN AND METHOD: Balb/c mice (male, 5 week-old) were treated with vehicle (n = 5), doxorubicin (20 mg/kg, i...
September 2016: Journal of Hypertension
Mukesh Madhukar Shete
Hypertension is one of the most common conditions seen in primary care and a major public health problem in India. It can lead to various complications if not detected early and treated appropriately. As per the latest Eighth Joint National Committee (JNC 8) the goal BP in most hypertensive patients age <60 years should be <140/90 mmHg and treatment can be started by selecting drugs from among 4 specific medication classes i.e. angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), calcium channel blocker (CCB) or diuretics...
April 2016: Journal of the Association of Physicians of India
J Tamargo, Luis Miguel Ruilope
Voltage-gated Ca(2+) channels are the primary route of Ca(2+) entry in vascular smooth muscle cells, playing a key role in the regulation of arterial tone and blood pressure. Since the 60´s, L-type Ca(2+) channel blockers (CCBs) have been widely used for the treatment of hypertension. Areas covered. T-type Ca(2+) channels regulate vascular tone in small-resistance vessels and aldosterone secretion, and N-type channels expressed in sympathetic nerve terminals regulate the release of neurotransmitters. We performed a literature search in MEDLINE, PubMed and ClinicalTrials...
October 4, 2016: Expert Opinion on Investigational Drugs
Yu Guan, Daisuke Nakano, Zhang Yifan, Akira Nishiyama
OBJECTIVE: Previous studies have indicated the beneficial effects of N-type calcium channel blocker, cilnidipine, on protecting renal podocyte injury in metabolic syndrome model rats. In the present study, we examined the effects of cilnidipine (L/N-type calcium channel blocker) and nifedipine (L-type calcium channel blocker) on the glomerular filtration barrier damage in the doxorubicin-induced nephropathy mice model. DESIGN AND METHOD: Balb/c mice (male, 5 week-old) were treated with vehicle (n = 5), doxorubicin (20 mg/kg, i...
September 2016: Journal of Hypertension
Tadashi Konoshita, Saori Kaeriyama, Machi Urabe, Takahiro Nakaya, Mika Yamada, Mai Ichikawa, Katsushi Yamamoto, Satsuki Sato, Michiko Imagawa, Miki Fujii, Yasukazu Makino, Yasuo Zenimaru, Shigeyuki Wakahara, Jinya Suzuki, Tamotsu Ishizuka, Hiroyuki Nakamura
The activation of the renin-angiotensin system (RAS) is one of the unfavourable characteristics of calcium channel blocker (CCB). N type calcium channel is thought to be involved in renin gene transcription and adrenal aldosterone release. Accordingly, N/L type CCB has a possibility of less elevation of plasma aldosterone concentrations (PAC) among CCBs. In a monotherapy study, we had already demonstrated that N/L type CCB leads to less activation of the RAS compared with L type CCB. The objective of this study is to substantiate the hypothesis that at the condition of additive administration on the top of an angiotensin receptor blocker (ARB), still N/L type CCB leads to less elevation of PAC compared with L type one...
October 2016: Bioscience Reports
Hongxia Zeng, Fan Wang, Bingqi Zhu, Weihui Zhong, Weiguang Shan, Jian Wang
RATIONALE: The structures of photodegradation impurities in cilnidipine were studied by liquid chromatography/Q-Orbitrap mass spectrometry (LC/Q-Orbitrap MS) for the further improvement of the official monographs in Pharmacopoeias. The complete fragmentation patterns of impurities were investigated to obtain their structural information. Two pathways of photodegradation of cilnidipine were also explored to clarify the source of impurities in cilnidipine. METHODS: Chromatographic separation was performed on a Boston Group C18 column (250 mm × 4...
August 15, 2016: Rapid Communications in Mass Spectrometry: RCM
Xin Cao, Yuji Nakamura, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsushi Sugiyama
A 53-year-old woman with end-stage renal disease and hypertension, who had received regular artificial hemodialysis for 10 years, has been treated with candesartan in a dose of 8 mg/day against her hypertension, but premature ventricular contractions were often observed during the hemodialysis. QT interval was 445 ms before hemodialysis, which was prolonged to 515 ms immediately after it, possibly reflecting the presence of reduced repolarization reserve in her heart. Since the blood pressure was often elevated to >160 mmHg before the hemodialysis, a daily dose of an L/N-type Ca(2+) channels blocker cilnidipine of 5 mg/day was added...
June 20, 2016: Heart and Vessels
Shoko Ohno, Hideki Yokoi, Kiyoshi Mori, Masato Kasahara, Koichiro Kuwahara, Junji Fujikura, Masaki Naito, Takashige Kuwabara, Hirotaka Imamaki, Akira Ishii, Moin A Saleem, Tomohiro Numata, Yasuo Mori, Kazuwa Nakao, Motoko Yanagita, Masashi Mukoyama
Pharmacological blockade of the N- and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of α1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2(-/-) mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2(-/-) mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2...
2016: Scientific Reports
Xin Cao, Yuji Nakamura, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Bingmei Zhu, Bin Xu, Akira Takahara, Masaki Saitoh, Atsushi Sugiyama
We assessed the anti-anginal effects of cilnidipine in comparison with those of nicardipine and nifedipine (1 and 10 µg/kg, n = 6 for each drug) or vehicle (n = 6) by using the vasopressin-induced angina model of rats. The administration of vasopressin (0.5 IU/kg, i.v.) to the rats depressed the S-wave level of the electrocardiogram reflecting the presence of subendocardial ischemia, whereas it significantly increased the mean blood pressure, resulting in the decrease of the heart rate and the prolongation of the PR interval possibly through a reflex-mediated increase in vagal tone...
May 18, 2016: Heart and Vessels
Man Liu, Ming Deng, Dan Zhang, Xiaolin Wang, Jingyi Ma, Hongna Zhao, Lina Zhang, Yang Tong, Huichen Liu
Efonidipine hydrochloride is a new generation dihydropyridine Ca(2+) channel blocker designed to inhibit both T-type and L-type Ca(2+) channels. Efonidipine possesses a chiral carbon and is clinically administered as a racemate. In the present study, an enantioselective and sensitive LC-MS/MS method of determining efonidipine enantiomers in human plasma was developed and validated to characterize the stereoselective pharmacokinetics. Plasma samples were processed by liquid-liquid extraction (LLE). Chiral separation was optimized on a CHIRALPAK(®) ID column using an isocratic mobile phase of acetonitrile/water (60:40, v/v)...
April 15, 2016: Journal of Pharmaceutical and Biomedical Analysis
Shoji Fukuda, Yuji Nakamura, Koso Egi, Shunichiro Fujioka, Satoshi Nagasaka, Pham Ngoc Minh, Koji Toguchi, Takeshi Wada, Hiroko Izumi-Nakaseko, Kentaro Ando, Tetsuya Mizoue, Kenji Takazawa, Shigeru Hosaka, Atsushi Sugiyama
Direct vasodilator effects of nitroglycerin, nifedipine, cilnidipine and diltiazem on human skeletonized internal mammary artery graft harvested with ultrasonic scalpel were assessed in the presence of 0.1 or 0.2 µM of noradrenaline. Ring preparations were made of distal end section of the bypass grafts, and those dilated by acetylcholine were used for assessment. Each drug dilated the artery in a concentration-related manner (0.01-10 µM, n = 6 for each drug) with a potency of nitroglycerin > nifedipine = cilnidipine > diltiazem...
October 2016: Heart and Vessels
Rama Mohan Pathapati, Sujith Tumkur Rajashekar, Madhavulu Buchineni, Rajesh Kumar Meriga, Chirra Bhakthavasthala Reddy, Kolla Praveen Kumar
INTRODUCTION: Hypertension is a major cardiovascular risk factor, which affects both large and small arteries. Because of the associated morbidity and mortality and the cost to society, it is an important public health challenge. Population based studies have reported that large artery stiffness is an important determinant of cardiovascular events and mortality in general population and in patients with hypertension. This study was designed to compare the effects of 8 weeks blood pressure control using Amlodepine and cilnidipine on haemodynamic parameters and vascular indices in mild to moderate hypertensive patients...
November 2015: Journal of Clinical and Diagnostic Research: JCDR
V K Singh, A Mishra, K K Gupta, R Misra, M L Patel, Shilpa
The aim of our study was to find out the antiproteinuric effect of enalapril angiotensin-converting enzyme (ACE inhibitor) alone or in combination with cilnidipine in patients with type-2 diabetes mellitus. The study was conducted on 71 patients with type-2 diabetes mellitus patients with hypertension and microalbuminuria. They were divided into two groups randomly as follows: Group I (enalaprilalone, n = 36) and Group II (enalapril with cilnidipine, n = 35). In both the groups, baseline 24 h urinary albumin was estimated and was repeated every 3 months upto 1-year...
November 2015: Indian Journal of Nephrology
Daniel Duda-Seiman, Corina Duda-Seiman, Florin Borcan, Livia-Cristina Borcan, Silvia Mancas, Speranta Avram
Calcium channel blockers (CCB) are widely used in cardiovascular medicine expressing high hopes upon decreasing cardiovascular risk, morbidity and mortality. Here, the potency of CCBs on 58 Romanian asymptomatic hypertensive patients, with no atherothrombotic cardiovascular disease, was studied by clinical and in silico methods. In our study, arterial elasticity/stiffness was assessed; anthropometric, metabolic (lipidic) parameters were quantified. We concluded that lercanidipine 10 mg once daily, during three weeks, is able to dramatically improve central aortic systolic blood pressure, aortic pulse wave velocity...
2015: Cardiovascular & Hematological Agents in Medicinal Chemistry
Jeong-Woo Son, Hojin Choi, Arum Yoo, Hyun-Hee Park, Young-Seo Kim, Kyu-Yong Lee, Young Joo Lee, Seong-Ho Koh
Cerebral infarction causes permanent neuronal loss inducing severe morbidity and mortality. Because hypertension is the main risk factor for cerebral infarction and most patients with hypertension take antihypertensive drugs daily, the neuroprotective effects and mechanisms of anti-hypertensive drugs need to be investigated. Cilnidipine, a long-acting, new generation 1,4-dihydropyridine inhibitor of both L- and N-type calcium channels, was reported to reduce oxidative stress. In this study, we investigated whether cilnidipine has therapeutic effects in an animal model of cerebral infarction...
October 2015: Journal of Neurochemistry
Jean Peters, Andrew Booth, Ruth Peters
BACKGROUND: There is some evidence to suggest a possible association between calcium channel blocker (CCB) use and a lower decline in cognitive function compared with use of other hypertensive treatments. In particular, there is an emerging interest in the potential for specific CCBs, particularly the dihydropyridine CCBs nitrendipine, nicardipine, cilnidipine, lercandipine, nimodipine, azelnidipine and nilvadipine. The aim of this review was to assess the evidence relating to these specific CCBs and incident cognitive decline or dementia in humans...
July 2015: Therapeutic Advances in Chronic Disease
Iulia Glovaci, C Andrew Chapman
The lateral entorhinal cortex receives strong inputs from midbrain dopamine neurons that can modulate its sensory and mnemonic function. We have previously demonstrated that 1 µM dopamine facilitates synaptic transmission in layer II entorhinal cortex cells via activation of D1-like receptors, increased cAMP-PKA activity, and a resulting enhancement of AMPA-receptor mediated currents. The present study assessed the contribution of phosphatidylinositol (PI)-linked D1 receptors to the dopaminergic facilitation of transmission in layer II of the rat entorhinal cortex, and the involvement of phospholipase C activity and release of calcium from internal stores...
2015: PloS One
Suparna Sacchit Bakhle, Jasmine Gev Avari
The present investigations highlight the development of solid self-emulsifying drug delivery system (solid-SEDDS) for improved oral delivery of the poorly water-soluble drug; cilnidipine. Liquid SEDDS of the drug were formulated using Capryol 90 as the oil phase, Tween 80 as the surfactant, and Transcutol HP as the co-surfactant after screening various vehicles. The prepared systems were characterized for self-emulsification time, robustness to dilution, % transmittance, globule size, drug release, and thermodynamic stability...
2015: Chemical & Pharmaceutical Bulletin
Ryoji Nishioka, Shunsuke Kinoshita, Michio Shiibashi, Tomokazu Shimazu, Yoshihiko Nakazato, Toshimasa Yamamoto, Naotoshi Tamura, Nobuo Araki
BACKGROUND: It has been suggested that antihypertensive drug therapy is attributable to the lower blood pressure variability, we investigated the effects of 4 classes of antihypertensives on the blood pressure variability; in addition, we also compared the effects among 4 calcium channel blockers. METHODS: We measured the 24-hour blood pressure variability in 309 patients with a history of cerebrovascular disease treated with angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, β blocker, or calcium channel blocker...
August 2015: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Yumi Koike, Tetsuya Kawabe, Kanami Nishihara, Naomi Iwane, Takuzo Hano
Pupillometry was used to evaluate the effects of the calcium channel blockers cilnidipine (CL) and amlodipine (AM) on changes in autonomic nervous activity induced by isometric exercise in patients with hypertension. After handgrip exercise, the velocity of miosis increased in both the CL and AM groups. However, the velocity of mydriasis increased in only the AM group. Velocity slopes of miosis and mydriasis were smaller in the CL group than in the AM group. The low-to-high frequency ratio obtained from pulse wave analysis increased in only the AM group...
2015: Clinical and Experimental Hypertension: CHE
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