Cilnidipine Group Research Articles

A Prospective, Randomized Open-Label Study for Assessment of Antihypertensive Effect of Telmisartan Versus Cilnidipine Using Ambulatory Blood Pressure Monitoring (START ABPM Study).

The antihypertensive agent telmisartan is an angiotensin II receptor blocker with a terminal elimination half-life of 24 h and has a high lipophilicity, thereby enhancing its bioavailability. Another antihypertensive agent, cilnidipine is a calcium antagonist and has dual mode of action on the calcium channels. This study aimed at determining effect of these drugs on ambulatory blood pressure (BP) levels. A randomized, open-label, single-center study was conducted during 2021 - 2022 on newly diagnosed adult patients with stage-I hypertension, in a mega city of India. Forty eligible patients were randomized to telmisartan (40 mg) and cilnidipine (10 mg) groups, with once daily dose administered for 56 consecutive days. Ambulatory blood pressure monitoring (ABPM) (24 h) was performed pre- and post-treatment, and the ABPM-derived parameters were compared statistically. Statistically significant mean reductions were observed in all BP endpoints in telmisartan group but only in 24-h systolic blood pressure (SBP), daytime and nighttime SBP, and manual SBP and diastolic blood pressure (DBP) in cilnidipine group. The mean change from baseline to day 56 between two treatment groups showed statistical significance in last 6-h SBP (P = 0.01) and DBP (P = 0.014), and morning SBP (P = 0.019) and DBP (P = 0.028). The percent nocturnal drop within and between groups was statistically nonsignificant. Also, the between group mean SBP and DBP smoothness index differed nonsignificantly. Telmisartan and cilnidipine once daily were effective and well tolerated in the treatment of newly diagnosed stage-I hypertension. Telmisartan provided sustained 24-h BP control and may offer advantages over cilnidipine in terms of BP reductions, particularly over the 18- to 24-h post-dose period or critical early morning hours.

A Retrospective, Observational, EMR-Based Real-World Evidence Study to Assess the Incidence of Pedal Edema in Essential Hypertensive Patients on Amlodipine or Cilnidipine.

Introduction Calcium channel blockers have pedal edema as one of the confining factors of treatment. A real-world study may help evident reality of the situation in regular Indian clinical practice. The aim of the study is to assess effectiveness and incidence of pedal edema in essential hypertensive patients treated with amlodipine or cilnidipine monotherapy. Methods Retrospective EMR data of adult essential hypertensive patients, prescribed amlodipine (n = 800) or cilnidipine (n = 800) as monotherapy, were analyzed. Incidence of pedal edema from baseline visit was analyzed in terms of dose and duration of treatment. The changes in systolic (SBP) and diastolic blood pressure (DBP) from baseline and proportion of patients achieving target BP goals were assessed. Results In amlodipine and cilnidipine groups, mean changes in SBP and DBP from baseline to end of the study period were 28.4 and 15.1 mmHg and 24.3 and 13.5 mmHg, respectively (p value <0.05). More than 50% of patients in both groups achieved BP goal at the end of the study (p value 0.266). In amlodipine group, total 23.9% reported pedal edema, while in cilnidipine, 27.6% (p value 0.0863). At the end of the study, 3.5% and 8.2% of patients remain with pedal edema, respectively, in both groups (pvalue <0.005). Conclusion Amlodipine demonstrated greater BP reduction at a lower average dose, better efficacy, and tolerability in terms of pedal edema count as a lesser number of patients reported edema at the end of the study and a higher percentage of patients continued the prescribed baseline dosage regimen as compared to cilnidipine. Thus, the study established amlodipine as an effective and well-tolerated antihypertensive for Indians.

Effects of the L/N-Type Ca2+ Channel Blocker Cilnidipine on the Cardiac Histological Remodelling and Inducibility of Atrial Fibrillation in High-Salt-Fed Rats.

High salt intake has been shown to induce hypertrophy and fibrosis in the atria and ventricles, which could result in the development of atrial fibrillation (AF). Whereas the development of AF is suggested to be prevented by renin-angiotensin system (RAS) inhibitors, recent findings have indicated that this prevention is closely associated with their antihypertensive effects. In this study, we investigated whether the L/N-type Ca2+ channel blocker cilnidipine counteracts salt-induced atrial and ventricular remodelling and the inducibility of AF. Cilnidipine was orally administered to Dahl salt-sensitive rats fed with an 8% NaCl diet at 10 mg/kg for 5 weeks, and then electrophysiological evaluation and histological analyses were performed. The effects were compared with those of the L-type Ca2+ channel blocker amlodipine at 3 mg/kg. Following the intake of the 8% NaCl diet, the blood pressure (BP) increased, and fibrosis was induced in the atria and ventricles. Cilnidipine decreased BP, and the extent of the decrease in the cilnidipine group was similar to those in the amlodipine group. Cilnidipine produced a greater decrease in the fibrotic area in the atria and ventricles than amlodipine. The cilnidipine group shortened the AF duration from 7.43 ± 3.16 to 2.95 ± 1.73 s, which had been increased by NaCl intake. Plasma noradrenaline levels in the cilnidipine group were lower than those in the amlodipine group. Thus, the suppressive effects of cilnidipine on the salt-induced atrial and ventricular remodelling, fibrosis, and AF sustainability might be closely associated with its N-type Ca2+ channel-blocking actions.

Effects of L-/N-Type Calcium Channel Blockers on Angiotensin II-Renin Feedback in Hypertensive Patients.

Objectives Cilnidipine, an L-/N-type calcium channel blocker (CCB), has unique organ-protective properties due to suppression of hyperactivity in the sympathetic nervous system and renin-angiotensin system (RAS). In this study, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing the RAS. Methods A total of 25 hypertensive patients receiving a RAS inhibitor were randomly assigned to a cilnidipine (n = 12) or amlodipine (n = 13) group. The effects of cilnidipine on proteinuria and angiotensin II–renin feedback were assessed. Results After 6 months of treatment, both systolic and diastolic blood pressures were significantly reduced to a similar extent in both groups. The urine albumin-to-creatinine ratio was significantly lower in the cilnidipine group (p < 0.05) than in the amlodipine group. Amlodipine increased plasma angiotensin I and angiotensin II levels (p < 0.05), whereas cilnidipine did not. Interestingly, the cilnidipine group had a higher ratio of angiotensin-(1–7) (Ang-(1–7)) to angiotensin II in plasma than the amlodipine group (p < 0.05). Conclusions The L-/N-type CCB cilnidipine, but not amlodipine, decreased urinary albumin excretion in hypertensive patients. Cilnidipine also increased the ratio of Ang-(1–7) to angiotensin II in plasma, which might be one factor underlying its beneficial effects.

A comparative study between cilnidipine and amlodipine on learning and memory in albino mice

Background: Alzheimer’s disease (AD) is the leading cause of dementia, followed by vascular dementia (VaD). Animal studies have shown that amlodipine improves learning and memory. Since, cilnidipine produces lesser side effects than amlodipine, and animal studies have shown that it has neuroprotective action, this study was conducted to evaluate the effect of cilnidipine on learning and memory and its comparison with amlodipine in alprazolam induced amnesic albino mice.Methods: This study was carried out on albino mice, divided into three groups of six animals each. Amnesia was induced by intraperitoneal injection of alprazolam in all the three groups from day 1 to 14. In addition, group 1, 2 and 3 received normal saline as a control, amlodipine and cilnidipine as test drugs respectively, by same route for the same duration. Then, learning and memory of the animals was assessed using elevated plus maze and cook’s pole climbing models. Results were compared among the groups using one-way ANOVA followed by post hoc Tukey’s test.Results: In both the model’s amlodipine and cilnidipine groups showed statistically significant reduction in transfer latency and conditioned avoidance response duration in comparison with normal saline. But no difference was found between amlodipine and cilnidipine groups.Conclusions: Cilnidipine and amlodipine showed a non-inferiority response on learning and memory enhancing effect in this study. Since, cilnidipine has lesser side effects than amlodipine, it can be taken up for evaluating its effect on cognitive improvement in dementia patients.

An N-/L-type calcium channel blocker, cilnidipine, suppresses autonomic, electrical, and structural remodelling associated with atrial fibrillation

Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC inhibition on such remodelling is unknown. Here, we investigated the ability of a clinically available Ca2+-channel blocker (CCB) with NTCC-blocking activity to suppress the arrhythmogenic effects of AF-promoting remodelling in dogs. Mongrel dogs were kept in AF by right atrial tachypacing at 600 bpm. Four groups were studied under short-term AF (7 days): (i) Shams, instrumented but without tachypacing (n = 5); (ii) a placebo group, tachypaced while receiving placebo (n = 6); (iii) a control tachypacing group receiving nifedipine (10 mg orally twice-daily; n = 5), an L-type CCB; and (iv) a cilnidipine group, subjected to tachypacing and treatment with cilnidipine (10 mg orally twice-daily; n = 7), an N-/L-type CCB. With cilnidipine therapy, dogs with 1-week AF showed significantly reduced autonomic changes reflected by heart rate variability (decreases in RMSSD and pNN50) and plasma norepinephrine concentrations. In addition, cilnidipine-treated dogs had decreased extracellular matrix gene expression vs. nifedipine-dogs. As in previous work, atrial fibrosis had not yet developed after 1-week AF, so three additional groups were studied under longer-term AF (21 days): (i) Shams, instrumented without tachypacing or drug therapy (n = 8); (ii) a placebo group, tachypaced while receiving placebo (n = 8); (iii) a cilnidipine group, subjected to tachypacing during treatment with cilnidipine (10 mg twice-daily; n = 8). Cilnidipine attenuated 3-week AF effects on AF duration and atrial conduction, and suppressed AF-induced increases in fibrous-tissue content, decreases in connexin-43 expression and reductions in sodium-channel expression. Cilnidipine, a commercially available NTCC-blocking drug, prevents AF-induced autonomic, electrical and structural remodelling, along with associated AF promotion.

A comparative study of the efficacy of cilnidipine and amlodipine used for the treatment of hypertension at tertiary health-care center

Background: One of the major problems in treatment patients of hypertension (HTN) is controlling their systolic blood pressure (SBP) and diastolic BP (DBP). Aims and Objectives: This study aims to study the efficacy of cilnidipine and amlodipine used for the treatment of HTN at tertiary health-care center. Materials and Methods: The present study was undertaken by the Department of Pharmacology in collaboration with the Department of Medicine on newly diagnosed patients of HTN attending medicine outpatient department of Bidar Institute of Medical Sciences, Bidar, for a period of 9 months from May 2018 to January 2019. 100 patients aged 18–60 years of either sex were included in the study. Data were analyzed using the SPSS version 22.0. Quantitative data are presented as means and standard deviation (SD) (mean ± SD). Results: After 8 weeks of treatment, a gradual decline in SBP from 149.2 ± 12.57 at baseline to 131.04 ± 6.02 and DBP from 94.22 ± 6.76 at baseline to 84.36 ± 1.79 was noted in cilnidipine group. Gradual decline in SBP from 151.56 ± 10.21 at baseline to 132.72 ± 4.91 and DBP from 95.4 ± 5.70 at baseline to 82 ± 2.55 was noted with amlodipine group. Statistical analysis using paired t-test was obtained which is statistically significant, P = 0.00001. Conclusion: It can be concluded that both the drugs significantly reduced BP, but cilnidipine found superior to amlodipine for reducing systolic BP and equally efficacious in reducing DBP.

A13716 Impacts of cilnidipine on blood pressure elevation during hemodialysis in patients with intradialytic hypertension

Objectives: Intradialytic hypertension (HTN) is one of the poor prognostic markers and may be associated with sympathetic overactivity. L/N-type calcium channel blocker cilnidipine was reported to suppress sympathetic nerves activity and lower blood pressure (BP). Methods: Fifty-one patients with end-stage renal disease on chronic hemodialysis who had intradialytic HTN (systolic BP elevation > 10 mmHg during hemodialysis) and no fluid overload were randomized into 2 groups: control and cilnidipine groups. Patients in cilnidipine group took cilnidipine (10 mg/day) for 12 weeks. The primary endpoint was the change in intradialytic systolic BP elevation before and after the 12 weeks of the intervention. Results: Before the intervention, no differences were observed in age, gender or pre-dialytic systolic BP (148.5 ± 12.9 vs. 148.3 ± 19.3 mmHg) between the 2 groups. Intradialytic systolic BP elevation was unchanged in control group. Cilnidipine significantly lowered post-dialytic systolic BP and thus appeared to attenuate intradialytic SBP elevation from 12.0 ± 15.4 mmHg to 4.8 ± 10.1 mmHg. However, this observed difference in intradialytic systolic BP elevation by cilnidipine did not reach a statistical significance. Catecholamine was unaffected in either group. Conclusion: Although cilnidipine failed to attenuate intradialytic systolic BP elevation in patients with intradialytic HTN, cilnidipine decreased both pre- and post-dialytic BP. Therefore, cilnidipine may be effective to lower systolic BP during HD in patients with intradialytic HTN.

The effect of an L/N-type calcium channel blocker on intradialytic blood pressure in intradialytic hypertensive patients

ABSTRACTBackground: Intradialytic hypertension (HTN), which is one of the poor prognostic markers in patients undergoing hemodialysis, may be associated with sympathetic overactivity. The L/N-type calcium channel blocker, cilnidipine, has been reported to suppress sympathetic nerves activity in vivo. Therefore, we hypothesized that cilnidipine could attenuate intradialytic systolic blood pressure (SBP) elevation. Methods: Fifty-one patients on chronic hemodialysis who had intradialytic-HTN (SBP elevation ≥10 mmHg during hemodialysis) and no fluid overload were prospectively randomized into two groups: control and cilnidipine groups. Cilnidipine group patients took cilnidipine (10 mg/day) for 12 weeks. The primary endpoint was the change in the intradialytic SBP elevation before and after the 12-week intervention. Results: Before the intervention, no differences were observed in age, sex or pre-dialytic SBP (148.5 ± 12.9 vs. 148.3 ± 19.3 mmHg) between the two groups. Intradialytic SBP elevation was unchanged in the control group. Cilnidipine significantly lowered the post-dialytic SBP with an attenuation of the intradialytic SBP elevation from 12.0 ± 15.4 mmHg to 4.8 ± 10.1 mmHg. However, the observed difference in the intradialytic SBP elevation by cilnidipine did not reach statistical significance (group×time interaction effect p = 0.25). Cathecolamine levels were unaffected by the intervention in both groups. Conclusion: Cilnidipine lowers both the pre- and post-dialytic SBP and might attenuate intradialytic SBP elevation. Therefore, cilnidipine may be effective in lowering SBP during HD in patients with intradialytic-HTN.

A randomized open-label study to compare the effects of amlodipine and cilnidipine on heart rate and proteinuria in subjects with hypertension with proteinuria

Background: Calcium channel blockers (CCBs) are a commonly used class of drugs for the treatment of hypertension. Cilnidipine is a novel CCB with a dual L/N-type CCB property, thus favoring additional renal and cardiovascular protection. Aims and Objectives: The aims of this study were to evaluate the effects and their linearity across the time frame of amlodipine and cilnidipine in hypertensive subjects with proteinuria on heart rate and proteinuria. Materials and Methods: A prospective, randomized, open-label study was carried out on hypertensive subjects with proteinuria attending the General Medicine OPD in K.R Hospital, Mysore. 60 subjects satisfying the inclusion and exclusion criteria were included in the study. Heart rate and urine protein-to-creatinine ratio (UPCR) were measured at baseline and at 12 weeks along with weekly heart rate monitoring. The dose of amlodipine and cilnidipine was titrated depending on the blood pressure control. Descriptive statistics, independent sample t-test, repeated measure ANOVA, and Cramer’s V-test were used to analyze the results. Results: Demographic profile was well matched in both the groups. The heart rate was significantly higher at 12 weeks in subjects treated with amlodipine, while subjects in the cilnidipine group showed a significantly higher heart rate compared to baseline (P < 0.05). Furthermore, while the UPCR was significantly decreased in the cilnidipine group, a significant increase was seen in the amlodipine group, thereby resulting in a significant intergroup difference (P < 0.05). Conclusion: Cilnidipine is, thus, a better alternative in hypertensive patients with proteinuria due to its cardioprotective and renoprotective actions.

Antiproteinuric effects of cilnidipine and amlodipine as add on therapy in hypertensive patients with chronic renal disease: a comparative study

Background: Cilnidipine is a dual blocker of L type and N type calcium channel and dilates both afferent and efferent arterioles. Hence it increases renal blood flow and reduces glomerular pressure ultimately reducing proteinuria. Thus, it may exert renoprotective effects. The present study was designed to compare the antiproteinuric effects of cilnidipine and amlodipine in hypertensive patients with chronic kidney disease as add on therapy to patients on losartan.Methods: This is a randomized, open label, prospective, parallel group study conducted in the out patient Department of Nephrology. The trial enrolled Diabetic CKD patients with hypertension and with spot urine protein creatinine ratio (PCR) ≥0.2 who were being treated with T. Losartan 50mg/day for &gt;2 months. The subjects were then randomly assigned to 2 groups to receive either cilnidipine 10-20mg/day (Group A-46) or amlodipine 5-10mg/day (Group B- 50). The drugs were given for a duration of 6 months for each patient. The dose of losartan (50mg/day) was not adjusted throughout the study.Results: After 6 months, a significant reduction in systolic and diastolic blood pressure was seen in both the groups. The decrease in urinary protein creatinine ratio was significantly higher in cilnidipine group rather than amlodipine group. Thus, cilnidipine exerted greater antiproteinuric effect than amlodipine.Conclusions: Cilnidipine has antihypertensive effect equivalent to amlodipine but addition of cilnidipine rather than amlodipine to losartan decreased urine protein excretion in diabetic chronic kidney disease patients.

Comparison of efficacy and safety of cilnidipine and losartan in patients of hypertension with or without diabetes from Gwalior, India

Background: Hypertension (HTN) is the most common cardiovascular disease. The objectives of present study are to investigate the comparison between cilnidipine and losartan with respect to changes in blood pressure (BP) and heart rate (HR) in hypertensive patients with or without type 2 diabetes mellitus (DM).Methods: We conducted a longitudinal, prospective, open labelled, comparative clinical study of hypertensive patients with or without type 2 DM. Of 161 enrolled hypertensives, 130 completed the study with follow up over a period of one year. Group I (n=34); and Group III (n = 32) patients with type 2 DM received cilnidipine 10-20mg orally OD. Group II (n =33); and Group IV (n = 31) patients with type 2 DM received losartan 50-100mg orally OD. The dosages were adjusted if the magnitude of reduction was insufficient. The parameters were monitored during follow – up at 4, 8 and 12 weeks.Results: Levels of systolic and diastolic BP and HR significantly decreased with both drugs. However, magnitude of HR reduction was greater with cilnidipine groups as compared to losartan groups with statistically significant difference (group I 70.79±9.21 versus group II 79.42±8.25, p = 0.000 and group III 76.25±7.08 versus group IV 81±7.15, p = 0.010). Of 161 patients, only 1 patient experienced hot flushes from group I.Conclusions: The present study demonstrated that therapy with cilnidipine can be used safely and effectively in hypertensive patients with or without diabetes. Cilnidipine was equally efficacious in lowering BP, while it more effectively reduced HR as compared to losartan. Cilnidipine can, therefore, be recommended as an alternative especially when there is associated tachycardia.

A Comparative study to assess the effectiveness and safety of cilnidipine versus amlodipine in patients with newly diagnosed essential hypertension: insights from a single centre prospective observational study

Background: Calcium channel blockers (CCBs) are proposed to play a pivotal role for the management and control of hypertension. Dihydropyridine-type calcium channel blockers (CCBs) like Amlodipine are frequently used because for their strong antihypertensive and minimal adverse side effects. However, it is commonly associated with the causation of pedal edema among the patients. Cilnidipine, which is a novel new generation calcium channel blocker, is presumed to cause lesser pedal edema with a satisfactory clinical control of hypertension along with negligible side effects. This study was carried out to compare clinical effectiveness and safety profile between Amlodipine and Cilnidipine.Methods: A prospective, randomized, open label study of 12 weeks’ duration was conducted amongst 60 patients with newly diagnosed essential hypertension. 30 patients of one group received Tab. Amlodipine 5 mg and 30 patients of same age groups received Tab. Cilnidipine 10mg.Results: There was a highly statistically significant decrease in the level of blood pressure in the Cilnidipine group compared to the Amlodipine group mainly at day 90 (P&lt;0.001). Cilnidipine treated group had a fall in blood pressure of 23 ± 8 mmHg and the Amlodipine group had a decrease in the blood pressure of 12±7mmHg. Additionally, there was also significant reduction in pulse rate in the cilnidipine group. Only 4 patients in the Cilnidipine group developed ankle edema which completely disappeared at the end of 12 weeks of therapy compared to 9 patients in the Amlodipine group which persistently worsened at the completion of the study.Conclusions: Our study concluded that cilnidipine was a well-tolerated anti-hypertensive drug amongst patients with newly diagnosed essential hypertension and associated with minor adverse effects.

A Comparative Study on Clinical and Biochemical Parameters in Amlodipine and Cilnidipine Treated Hypertensive Patients.

Hypertension is a major health issue worldwide. Calcium Channel Blockers (CCBs) are the most commonly used antihypertensive agents. CCBs act on voltage-dependent calcium channels and they were categorized into two subclasses, Dihydropyridine (DHP) and non-Dihydropyridine (non-DHP) derivative. Amlodipine is a third generation L-type of DHP and Cilnidipine is a novel L/N-type of DHP CCB, both drugs have excellent pharmacological profiles with the unique actions. To study the clinical and biochemical profile in Amlodipine and Cilnidipine treated mild to moderate hypertensive patients. The present study was a cross-sectional study. A total of 140 mild to moderate hypertensive patients (HTN classified according to Joint National Committee-8 (JNC-8) HTN guideline), 70 were in Amlodipine group (Group-A), and other 70 patients were in Cilnidipine group (Group-B). Group-A receiving Tab Amlodac 5 mg/day and Group-B receiving Tab Cilacar 10 mg/day, and both the group receiving respective medications since more than six months. Patients enrolled into the study with due consideration of eligibility criteria. Demographic, clinical and biochemical parameters were noted and compared. Demographic parameters are matched, there was no significant difference seen between two study groups. Systolic and Diastolic Blood Pressure (SBP and DBP) showed a significant difference (p<0.001). There was no significant difference in pulse rate between the two groups, both QT/QTc showed statistically significant difference (p<0.001). The biochemical parameters like serum creatinine, albumin, globulin, total protein, serum Na+, fractional excretion of Na+, serum osmolality, vanillyl mandelic acid, were compared between two study groups, there was no significant difference seen between the two groups. The Amlodipine and Cilnidipine both are equally effective antihypertensive drugs. Cilnidipine treated group showed more reduction in blood pressure than the Amlodipine treated group and there was no significant change in heart rate between the two groups. Cilnidipine group showed comparatively shortened QT/QTc interval than the Amlodipine group.

Comparison of the effects of L-type calcium channel antagonist Amlodipine with L/N-type calcium channel antagonist Cilnidipine on blood pressure, heart rate, proteinuria and lipid profile in hypertensive patients

Background: Cilnidipine is a novel and unique 1,4-dydropyridine derivative calcium antagonist that exerts potent inhibitory actions not only on L-type but also on N-type voltage dependent calcium channels. Blockade of the neural N-type calcium channel inhibits the secretion of norepinephrine from peripheral neural terminals and depresses sympathetic nervous system activity.Objective and methods: The purpose of this study was to assess the effect of Cilnidipine and Amlodipine on blood pressure (BP) levels. We did BP monitoring before and after once-daily use of Cilnidipine and Amlodipine in 100 hypertensive patients.Results: Both drugs significantly reduced systolic BP (SBP) and diastolic BP (DBP). However, the reductions in pulse rate (PR) were significantly greater in the Cilnidipine group than the Amlodipine group. N-type calcium channel blockade by Cilnidipine may not cause reflex tachycardia, and may be useful for hypertensive treatment.Conclusion: There was significant reduction in proteinuria with Clindipine as compared to Amlodipine. However, there were no significant change in total cholesterol level in diabetes and non-diabetics in both the group.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.460-465

A clinical study of the effects of cilnidipine and amlodipine in hypertensive patient focusing on pedal edema

Introduction: Many Calcium channel blocker drugs for control of hypertension are available. New drug Cilinidipine is available and approved for treatment of hypertension. It acts by blocking both L-type and N-type voltage-dependent calcium channels. The neural N-type blockade leads to stoppage of the secretion of norepinephrine and it also depresses sympathetic nervous system activity. The aim of the study is to assess the effect of cilnidipine and amlodipine on hypertensive patient. Method: Clinidipine (n=50) and Amolodipine (n=50) were given once daily and BP was measured daily before and after the medicine in 100 hypertensive patients on OPD basis in GDMC, Dehradun. Result: Only 4 patients (n=50; 8%) in cilnidipine group developed edema within 10 days of therapy, while 32 patients (n=50, 64%) developed with edema within 10 days of treatment in amlodipine group. Conclusion: Cilnidipine is also associated with less incidences of pedal edema which is main complaint of patient. It controls BP better with less reflex tachycardia and decrease in morning surge.

Abstract TP103: Activation of the Pi3k Pathway Plays Important Roles in Reduction of Cerebral Infarction by Cilnidipine

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 daily antihypertensive drugs, the neuroprotective effects and mechanisms of anti-hypertensive drugs need to be investigated. Cilnidipine, a long-acting, second-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. After determination of the most effective dose of cilnidipine, a total of 128 rats were subjected to middle cerebral artery occlusion (MCAO). Neurobehavioral function test and brain MRI were performed, and rats with similar sized infarcts were randomized to either the cilnidipine group or the control group. Cilnidipine treatment was performed with reperfusion after 2-hr occlusion. Western blots and immunohistochemistry were also performed after 24-hr occlusion. Initial infarct volume on DWI was not different between the cilnidipine group and the control group; however, FLAIR MRI at 24 hr showed significantly reduced infarct volume in the cilnidipine group compared with the control group. Cilnidipine treatment significantly decreased the number of TUNEL-positive cells compared to the control group. Western blot and immunohistochemistry showed increased expression of phosphorylated Akt (Ser473), phosphorylated GSK-3β, and Bcl-2 and decreased expression of Bax and cleaved caspase-3. These results suggest that cilnidipine, which is used for the treatment of hypertension, has neuroprotective effects in the ischemic brain through activation of the PI3K pathway.

Effects of Cilnidipine on Heart Rate and Uric Acid Metabolism in Patients With Essential Hypertension.

BackgroundThe relation between hypertension and hyperuricemia has been established by epidemiological studies. Calcium channel blockers are one of the first-line drugs for newly diagnosed patients with essential hypertension. Cilnidipine is a new calcium channel blocker acting by blocking both L- and N-type calcium channels. The aim of this study was to compare the effectiveness of amlodipine and cilnidipine in patients with essential hypertension and their effects on heart rate and serum uric acid levels.MethodsOut of 100 enrolled patients, 92 completed the study. They were randomly assigned to amlodipine (N = 47) and cilnidipine (N = 45) groups. Cilnidipine was started at 10 mg/day and then adjusted to 5 - 20 mg/day, and amlodipine was started at 5 mg/day and then adjusted to 2.5 - 10 mg/day.ResultsAfter 24 weeks of study, patients in cilnidipine groups showed significant reduction in heart rate and serum uric acid levels from baseline (P = 0.00).ConclusionIn clinical setting where both hypertension and hyperuricemia exist, cilnidipine can be a promising drug of choice.

Activation of the phosphatidylinositol 3-kinase pathway plays important roles in reduction of cerebral infarction by cilnidipine.

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. After determination of the most effective dose of cilnidipine, a total of 128 rats were subjected to middle cerebral artery occlusion. Neurobehavioral function test and brain MRI were performed, and rats with similar sized infarcts were randomized to either the cilnidipine group or the control group. Cilnidipine treatment was performed with reperfusion after 2-h occlusion. Western blots and immunohistochemistry were also performed after 24-h occlusion. Initial infarct volume on diffusion-weighted MRI was not different between the cilnidipine group and the control group; however, fluid-attenuated inversion recovery MRI at 24h showed significantly reduced infarct volume in the cilnidipine group compared with the control group. Cilnidipine treatment significantly decreased the number of triphosphate nick end labeling-positive cells compared to the control group. Western blot and immunohistochemistry showed increased expression of phosphorylated Akt (Ser473), phosphorylated glycogen synthase kinase-3β, and Bcl-2 and decreased expression of Bax and cleaved caspase-3. These results suggest that cilnidipine, which is used for the treatment of hypertension, has neuroprotective effects in the ischemic brain through activation of the PI3K pathway. We investigated whether cilnidipine has neuroprotective effects on ischemic stroke in an animal model. We have demonstrated that the neuroprotective effect of cilnidipine is associated with the activation of the PI3K pathway. Considering the daily use of antihypertensive drugs for patients with hypertension, cilnidipine could be beneficial for patients with ischemic stroke.

Cilnidipine but not amlodipine suppresses sympathetic activation elicited by isometric exercise in hypertensive patients

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. Sympathetic activation elicited by isometric exercise was suppressed more effectively by CL than by AM.