The effects of chemically and electrically-induced convulsions on [H]Nitrendipine binding in mouse brain

The effects of chemically and electrically-evoked seizures on [³H]nitrendipine binding to voltage-dependent calcium channels in mouse brain were determined 30 and 60 min following the initiation of convulsions. While maximal electroconvulsive shock, pentylenetetrazol and strychnine exhibited either no or marginal effects, Ro 5-4864 produced a decrease (14%) in the B_max of [³H]nitrendipine at 30 min but not 60 min. The convulsant dihydropyridine calcium channel activator, BAY K 8644, produced a significant increase in the K_d (31%) of [³H]nitrendipine at 30 min, and a significant increase in both the B_max (21%) and K_d (28%) of [³H]nitrendipine 60 min following the initiation of convulsions. While maximal electroconvulsive shock, pentylenetetrazol and strychnine exhibited either no or marginal effects, Ro 5-4864 produced a decrease (14%) in the B_max of [³H]nitrendipine at 30 min but not 60 min following the initiation of convulsions. These findings indicate that modulation of voltage-dependent calcium channels by certain convulsants may be important in the genesis of seizures or in post-ictal compensatory processes.     

家兔血浆中尼群地平的气相色谱测定法

尼群地平是一种新型的钙拮抗剂,临床上用于治疗高血压。在碱性条件下用乙醚/环己烷(3/7)混合溶剂从血浆中提取尼群地平,在气相色谱上直接进样(OV—17柱,电子捕获检测器)。在3—30ng/ml浓度范围内,标准曲线呈线性。对家兔的药代动力学参数一并报道。     

Application of a self-modeling curve resolution method for studying the photodegradation kinetics of nitrendipine and felodipine

Dihydropyridine (DHP) derivatives, as calcium channel blockers with cardiovascular activity, are highly photosensitive and converted in the presence of light to compounds that are inactive. In this work, a self-modeling curve resolution method was applied to study the photodegradation kinetics of nitrendipine and felodipine by spectrophotometric method. The methanolic solutions of drugs were separately exposed to UV and daylight, respectively. A fully soft-modeling multivariate curve resolution method based on the combination of iterative target transformation and Kubista methods were used to analyze the recorded absorbance data, extracting the concentration profiles and pure spectra of the drugs and their photodegradation products. By fitting the concentration profiles of the studied DHP drugs to different kinetic equations, it was found that at the beginning of lighting, the reaction is zero-order and in the case of nitrendipine it changes to a first-order kinetic when the concentration of products exceeded than that of the initial compounds.     

Treatment of hypertensive emergency

Objective To present the efficacy and tolerability of a new oral dosage form of the calcium antagonist nitrendipine compared to nifedipine capsules in patients with hypertensive emergency.Design Multicenter randomized double blind clinical study.Setting 23 study centres (hospitals) in Germany.Patients 161 patients between 20 and 70 years with acutely elevated blood pressure (systolic 200–250 mmHg, diastolic between 110–140 mmHg) with and without concomitant clinical symptoms.Interventions Double blind treatment with 10 mg nifedipine or 5 mg nitrendipine. Nifedipine was administered as capsules, nitrendipine was given from a small plastic tube (vial), containing 1 ml alcoholic solution. Every patient received in addition to the test medication a placebo corresponding to the other product. Patients with insufficient treatment after 45 min were given either an additional capsule of 10 mg nifedipine or a further vial containing 5 mg nitrendipine according to their group and maintaining the double dummy procedure.Measurements and results Blood pressure and heart rate were measured repeatedly during 4 h, before and 90 min after beginning of the treatment a 12 channel resting ECG was recorded. At 45 min after administration the blood pressure had fallen significantly from 216.0/117.4 mmHg to 170.0/93.3 mmHg under nifedipine and from 216.9/117.3 mmHg to 177.4/94.4 mmHg under nitrendipine. 61.6% of the nifedipine patients and 58.8% of the nitrendipine patients had already reached blood pressure values <180/100 mmHg after 45 min and in both groups 83% of these patients were still in this limit at the end of the observation period after 4 h. Tolerability was very good in both groups.Conclusion The new dosage form of nitrendipine (vial with 1 ml of alcoholic solution) represents an alternative in the treatment of hypertensive emergency.     

Effect of calcium channel blockers on paraoxonase-1 (PON1) activity and oxidative stress

BackgroundIn this study, we investigated the in vitro effects of calcium channel blockers (nifedipine, nitrendipine, isradipine, and amlodipine besylate) on the activity of paraoxonase-1 (PON1).MethodsPON1 was purified from human serum using simple chromatographic methods, including DEAE-Sephadex anion-exchange and Sephadex G-200 gel filtration chromatography.ResultsThe calcium channel blockers decreased the in vitro PON1 activity. The inhibition mechanism of amlodipine besylate was noncompetitive, whereas nifedipine, nitrendipine, and isradipine were competitive inhibitors.ConclusionsOur results showed that calcium channel blockers exhibit inhibitory effects on PON1 at low concentrations. The IC₅₀ values for nifedipine, nitrendipine, isradipine, and amlodipine besylate were determined to be 0.121 mM, 0.130 mM, 0.255 mM, and 0.304 mM, respectively, and the K_i constants were calculated to be 0.222 ± 0.049 mM, 0.151 ± 0.067 mM, 0.286 ± 0.137 mM, and 0.321 ± 0.002 mM, respectively.     

西尼地平与尼群地平治疗高血压病的疗效比较

目的:比较西尼地平与尼群地平治疗高血压病的疗效及安全性。方法:86例原发性高血压病患者随机均分为西尼地平组和尼群地平组,西尼地平组给予西尼地平,起始剂量为5mg,qd,根据血压可调整至10mg,qd;尼群地平组给予尼群地平,起始剂量为10mg,qd,根据血压可调整至20mg,bid。比较2组的降压疗效及药品不良反应。结果:西尼地平组与尼群地平组的总有效率分别为90.7%和88.4%,2组比较差异无统计学意义(P>0.05);西尼地平组和尼群地平组收缩压的最大降幅分别为(34.2±3.8)和(29.2±2.2)mmHg,舒张压最大降幅分别为(23.8±2.6)和(19.4±2.3)mmHg,差异有统计学意义(P<0.05)。尼群地平组治疗后心率明显快于治疗前及西尼地平组治疗后(P<0.05),但西尼地平组患者心率治疗前、后无显著变化(P>0.05)。治疗过程中2组均未见明显不良反应发生。结论:西尼地平用于治疗高血压疗效与尼群地平相近,但其对患者的心率影响较小。     

美托洛尔联合尼群地平治疗原发性高血压的临床观察

目的:观察美托洛尔联合尼群地平治疗原发性高血压的临床效果。方法:将我院2008年1月-2010年6月收治的120例原发性高血压患者随机均分为对照组和观察组。对照组口服美托洛尔50mg,bid;观察组口服美托洛尔12.5mg,tid+尼群地平10mg,tid。治疗后,将2组患者的总有效率、不良反应发生率及治疗前后的心肌肥厚情况、血脂水平进行统计、比较。结果:观察组的治疗总有效率高于对照组(100.0%vs.93.3%,P<0.05),不良反应发生率低于对照组(5.0%vs.15.0%,P<0.05),治疗后观察组的心肌肥厚改善程度及血清甘油三酯(TG)、载脂蛋白B100(APO-B100)及低密度脂蛋白胆固醇(LDL-C)均低于对照组(P<0.05),而总胆固醇(TC)及高密度脂蛋白胆固醇(HDL-C)比较,则差异均无统计学意义(P>0.05)。结论:美托洛尔联合尼群地平可有效治疗原发性高血压,不良反应少,并能有效改善心肌肥厚程度及TG、APO-B100、LDL-C水平。     

尼群地平联用倍他乐克治疗原发性高血压46例疗效观察

目的：了解尼群地平联用倍他乐克治疗原发性高血压的疗效.方法：76例患者分为两组,尼群地平联用倍他乐克治疗组和单用尼群地平对照组,比较两组的疗效.结果：治疗组的显效率和总有效率分别为91.3%和97.8%,对照组的显效率和总有效率分别为73.3%和83.3%.结论：尼群地平联用倍他克治疗原发性高血压明显优于单用尼群地平.     

尼群地平对高血压病患者动脉和血液动力学的影响

本文用二维一脉冲多普勒超声心动图观察尼群地平对高血压患者动脉的效应。结果表明,尼群地平不仅扩张小动脉,降低外周阻力,使血压明显下降;增加动脉顺应性;直接扩张外周大动脉,改善外周循环;降低外周大动脉壁切线张力;而且不影响外周大动脉壁切应力。总之,尼群地平在高血压病患者,可产生良好的动脉效应。     

Prevention of Doca-Salt Hypertension with the Calcium Blocker Nitrendipine

Mononephrectomized female rats on a high sodium intake developed hypertension, hypokalemia, enlarged hearts and kidneys and slight adrenal involution under deoxycorticosterone treatment. Simultaneous administration of nitrendipine (5 mg/kg twice daily) completely prevented hypertension and reduced but did not abolish cardiac enlargement. There was no effect of the calcium slow-channel inhibitor on kidney enlargement, adrenal atrophy or hypokalemia. The ability of the steroid to produce cardiomegaly in the absence of an elevated blood pressure to account for it, tends to confirm the suggestion of other investigators that the steroid may have that effect by a mechanism not involving blood pressure elevation.