细辛与verapamil镇痛协同作用的实验研究

目的 研究细辛与verapamil的镇痛协同作用 ,为临床联合用药提供理论依据。方法 采用醋酸扭体实验及热板法致痛实验观测其镇痛作用 ,并用神经盒、多媒体MS 30 2系统观察其对蟾蜍坐骨神经动作电位的影响。结果 细辛及A V复方制剂对醋酸致小鼠腹痛、热板法致小鼠足痛均有明显的镇痛作用并能抑制蟾蜍坐骨神经动作电位的传导。verapamil有弱的镇痛作用 ,无坐骨神经动作电位阻滞作用。A V复方制剂的镇痛及抑制神经动作电位传导作用均大于其组分细辛和维拉帕米。

Na^(+)/Ca^(2+)交换体抑制剂SN-6和维拉帕米降低肾上腺皮质癌细胞系NCI-H295R醛固酮合成酶表达

目的研究Na^(+)/Ca^(2+)交换体(NCX)抑制剂SN-6和钙通道阻滞剂(CCB)维拉帕米对钾离子(K^(+))刺激的肾上腺皮质癌细胞系NCI-H295R(H295R)醛固酮合成酶表达的影响。方法H295R细胞分为对照组、K^(+)(15 mmol/L)处理组、钙通道阻滞剂维拉帕米(verapamil)(10μmol/L)处理组、SN-6(10μmol/L)处理组、K^(+)+维拉帕米处理组、K^(+)+SN-6处理组、维拉帕米+SN-6处理组和K^(+)+维拉帕米+SN-6处理组,用实时荧光定量PCR检测醛固酮合成酶(CYP11B2)的mRNA表达,用FLIPR Calcium6检测细胞内钙离子水平。结果与对照组相比,K^(+)刺激醛固酮合成酶CYP11B2的mRNA表达(P<0.001);SN-6和维拉帕米均抑制K^(+)刺激的CYP11B2的mRNA表达(P<0.01);与K^(+)+SN-6组相比,K^(+)+SN-6+维拉帕米组更能显著抑制CYP11B2的mRNA表达(P<0.001)。SN-6和维拉帕米显著降低K^(+)刺激的细胞内钙离子水平(P<0.0001)。结论SN-6和维拉帕米均抑制K^(+)诱导的H295R细胞的醛固酮合成酶的表达;SN-6联合维拉帕米处理,抑制作用更显著。

顺铂及增敏剂Verapamil、SDZ PSC 833诱导卵巢癌细胞凋亡的研究

目的 探讨顺铂及 Verapam il、SDZ PSC 833作用机制 ,探讨获得性耐药机制。方法 以人卵巢癌亲代细胞株COC1 及其耐药亚株 COC1 /DDP为材料 ,计算细胞生长抑制率、细胞凋亡率及进行细胞周期分析。结果 顺铂联用Verapamil或 SDZ PSC833可提高细胞生长抑制率 ;顺铂引起 S期细胞比例增高 ,大剂量顺铂造成 S期细胞大量凋亡 ;COC1 、COC1 /DDP凋亡率不同 ,PSC833能明显增强顺铂诱导 COC1 /DDP细胞凋亡。结论 Verapamil、PSC833有增敏作用 ,PSC833能增强顺铂诱导 COC1 /DDP细胞凋亡 ;诱导细胞凋亡是顺铂作用机制之一 ,获得性耐药与凋亡耐受有关 ;顺铂引起 S期细胞增多 ,凋亡细胞为

CP-154,526和verapamil对促肾上腺皮质激素释放因子分泌水平的影响

目的探讨促肾上腺皮质激素释放因子Ⅰ型受体(CRF-R1)拮抗剂CP-154,526(CP)和钙离子通道拮抗剂vera-pamil(VP)对幼年大鼠在缺氧缺血(HI)后并放置1天后血浆中促肾上腺皮质激素释放因子分泌水平的影响。方法 80只幼年大鼠随机分成8组,即对照组、假手术组、CP对照组、VP对照组、模型组(HI组)、HI+CP组、HI+VP组和HI+CP+VP组。用放射免疫法测定各组幼年大鼠血浆中CRF水平。结果与对照组比较,HI组、HI+CP组和HI+CP+VP组血浆CRF水平都显著降低(P<0.001、P<0.001、P<0.001);与假手术组比较,HI组、HI+CP组和HI+CP+VP组血浆CRF水平都显著降低(P<0.001、P<0.001、P<0.001);与CP对照组比较,HI组、HI+CP组和HI+CP+VP组血浆CRF水平都显著降低(P<0.001、P<0.001、P<0.001);与VP对照组比较,HI组、HI+CP组和HI+CP+VP血浆CRF水平都显著降低(P<0.001、P<0.001、P<0.001);与HI组比较,HI+CP组和HI+VP组血浆CRF水平显著增加(P<0.05、P<0.001);与HI+CP比较,HI+VP组血浆CRF水平显著增加(P<0.001);与HI+VP组比较,HI+CP+VP组血浆CRF水平显著降低(P<0.001)。结论幼年大鼠在HI后并放置1天后血浆CRF水平都显著减少;可是,当幼年大鼠用CP或者VP预处理后,血浆CRF分泌水平在缺氧缺血下的减少能被逆转;当用CP和VP同时预处理后,血浆CRF分泌水平在缺氧缺血下的减少没有被改变。

Verapamil和Mn^（2＋）对缺氧及缺氧复氧心肌细胞内pH的影响

采用荧光探针ＢＣＥＣＦ／ＡＭ结合计算机图像处理技术测定不同时间的缺氧和缺氧复氧单心肌细胞内ｐＨ的变化以及Ｃａ２＋通道阻滞剂Ｖｅｒａｐａｍｉｌ和Ｎａ＋－Ｃａ２＋交换抑制剂Ｍｎ２＋对其的影响。结果显示随着缺氧时间的延长，细胞内ｐＨ也逐渐降低。复氧开始４０ｍｉｎ内，细胞内ｐＨ并未恢复正常。Ｖｅｒａｐａｍｉｌ能减轻缺氧细胞内酸化程度并使其接近正常水平（Ｐ＞０．０５），却未能减轻缺氧复氧细胞内的酸化。无论是缺氧或缺氧复氧心肌细胞，Ｍｎ２＋均未能减轻细胞内的酸化程度。本实验结果提示缺氧和缺氧复氧时细胞内酸化途径并非完全一致。ＶｅｒａＰａｍｉｌ抑制缺氧细胞内ｐＨ下降是其保护缺氧心肌作用的机制之一。

HTK液与Verapamil配伍对供心保存效果的实验研究

目的通过建立Langendorff离体鼠心灌流模型,研究HTK液与Verapamil配伍对供心的保护效果。方法30只SD大鼠(200～400g/只),随机分为实验组与对照组,实验组予以HTK液与Verapamil(5mg/L)配伍、对照组予以单纯HTK液作为停搏液,建立标准的Langendorff离体心脏灌注模型,4℃低温下保存大鼠心脏6h,予以37℃K-H液复灌,心脏复跳,生理仪记录缺血前、复灌20min、40min、60min、80min时血流动力学标值,检测心脏复灌45min时冠脉流出液中心肌酶学指标,实验结束后各组留取样本以行常规病理切片及电镜切片观察微观结构变化。结果实验组LVSP平均恢复率高于对照组,对照组LVEDP持续上升,实验组LVEDP相对稳定;对照组心肌酶均明显高于实验组(P<0.05);病理切片显示对照组损伤较实验组明显。结论 HTK液联合Verapamil较单独使用HTK液作为心肌保护液,对心肌具有更明显的保护作用。

硫氮酮(diltlazem)和异扑定(Verapamil)治疗高血压时的血脂变化

本文对53例原发性高血压患者,用随机、双盲法分为两组,分别用硫氮酮和异扑定治疗,疗程4周。两组均显示明显的降压效果,前者的降压幅度又明显大于后者,治疗后的血脂改变为:（1）HDL-C,（HDL-C）/TC比值和（HDL-C）/（LDL-C）比值升高。（2）APOA1升高。这些改变均有利于防止动脉粥样硬化。从而认为。

Verapamil和Propranolol对非胰岛素依赖型糖尿病透析患者物质代谢的影响

比较Ｖｅｒａｐａｍｉｌ和Ｐｒｏｐｒａｎｏｌｏｌ对患有胰岛素非依赖型糖尿病及轻度至中度高血压的透析患者的血糖和物质代谢的影响。方法：４６例患有非胰岛素依赖型糖尿病及轻度至中度高血压的透析患者，为德国福尔达市ＫｆＨ血透中心和柏林ＫｆＨ血透中心的透析病人。分别经Ｖｅｒａｐａｍｉｌ和Ｐｒｏｐｒａｎｏｌｏｌ治疗三个月后测空腹血糖、血红蛋白Ａ１ｃ、果酸、胰岛素、胆固醇和甘油三脂，同时记录透析前心率和血压。结果：Ｖｅｒａｐａｍｉｌ对血糖及物质代谢无不良影响，Ｐｒｏｐｒａｎｏｌｏｌ可引起血糖、果酸和血红蛋白Ａ１ｃ升高。结论：在糖尿病透析患者。

Antineoplastic Effect of Calcium Channel Blocker-Verapamil and 5-Fluorouracil Intraperitoneal Chemotherapy on Hepatocarcinoma-Bearing Rats

Objective To study the antineoplastic effect of the calcium channel blocker verapamil and 5-fluorouracil intraperitoneal chemotherapy onhepatocarcinoma-bearing rats, and examine the action between calcium channel blockers and cytotoxic drugs.Methods We adopted the method of subcapsular implantation of carcinoma tissues of walker-256 in the left liver lobe as a model of livercarcinoma-bearing rats. All experimental animals were divided into four groups. On the sixth day post implantation, in group A (controlgroup) 6 ml of saline was injected intraperitoneally once a day for 3 days. In group B (single chemotherapy group) 6 ml of 5-Fu 75 mg/kg was injected intraperitoneally once a day for 3 days. In group C (combination of treatment group) both 5-Fu (75 mg/kg) and verapamil(25 mg/kg) were administered simultaneously as in A and B. In group D (simple verapamil group) only 6 ml of verapamil (25 mg/kg)was administered as above.Results Compared with groups A, B and D, The volume of cancer and the contents of liver cancer DNA and protein were significantlyreduced. The rates of inhibiting cancer (89.9% in group C and 35.4% in group B) were significantly increased in group C. Group C hadsignificantly long survival time compared to groups A, B and D ( P < 0.05) . By light microscopy, a number of focal necroses were foundin cancer tissue in group C.Conclusion Calcium channel blockers can enhance the antineoplastic effect of 5-Fu intraperitoneal chemotherapy to liver cancer ; Theuse of verapamil can not increase the toxicity of 5-Fu.

异搏定(verapamil)对急性缺氧复合失血性休克狗的心泵功能的影响

本文观察了Ca2+通道阻断剂——异搏定（verapamil）对急性缺氧复合失血性休克狗,回输血后心泵功能的影响。健康雄性家犬13只,体重8.5～16kg,戊巴比妥钠麻醉,在低压舱内（模拟高度4000m,大气压460mmHg）按wigger法自股动脉快速放血,在5min内使平均动脉压降至5.

In vitro growth inhibition of human colonic tumor cells by Verapamil

AIM: To investigate the effects and mechanisms of Verapamil on cultured human colonic tumor (HCT) cells.METHODS: HCT cells were treated with different concentrations of Verapamil, and their proliferation was examined by MTT assay. The areas of sub-diploid peak were measured by flow cytometry, and the DNA ladder was found by agarose gel electrophoresis. The characteristic changes in morphology were observed under light microscopy. The cell nuclei (propidium iodide labeled, PI-labeled) and cellular distribution and concentration of calcium (Fluo-3-labeled) were studied by using laser confocal scanning microscope.RESULTS: The proliferation of HCT cells was inhibited by different concentrations of Verapamil. With the increase in concentration of Verapamil, the percent of G0-G1 phase cells in HCT cells increased and that of S phase cells decreased. After treating with different concentrations of Verapamil, flow cytometry showed that HCT cells were enlarged in areas of sub-diploid in a dose-dependent manner. Gel electrophoresis results displayed a typical DNA ladder. On staining with Wrights-Giemsa, the typical cellular apoptosis morphologic changes were also observed. PI-labeled cell nuclei were found markedly changed. In addition, we inspected that the 100 μmol/L Verapamil could increase the intracellular calcium ion concentration [Ca2+]i in HCT cells.CONCLUSION: Verapamil can inhibit proliferation of HCT cells via inducing cell apoptosis.

Protective effects of verapamil on myocardial mitochondrial respiratory function after combined radiation－burn injury in rats

The effects of verapamil, a calcium antagonist, on arterial blood pressure and myocardial mitochondrial respiratory function were studied in rats after they were inflicted with 6 Gy irradiation and 30% TBSA full thickness burns. The preventive or therapeutic administration of verapamil exerted little effects on the arterial blood pressure but could effectively protect the myocardial mitochondrial respiratory function after combined radiation-burn injury in rats.The protective effects of verapamil might exercise through the reduction of calcium content in the mitochondria.

Verapamil inhibits scar formation after peripheral nerve repair in vivo

The calcium channel blocker,verapamil,has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro.It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue.In this study,the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No.10-0 suture.The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks.Compared with the control group（stoma wrapped with gelfoam soaked with physiological saline）,the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo,suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons.These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair.

Repurposing verapamil for prevention of cognitive decline in sporadic Alzheimer's disease

Dementia is currently the only leading cause of death that is still on the rise,with its overall costs already surpassing those of cancer and heart disease combined,it has developed into a worldwide crisis.In response to its serious and far-reaching effects,the US government has established the"National Alzheimer's Project Act"(Public Law 111-375).

Verapamil and vasospastic angina： underuse in the elderly population

The first case of Prinzmetal angina was described in 1959 by Prinzmetal, et al. Since this description, several triggering factors have been associated with vasospastic angina （VA） and included： illicit drugs such as cocaine, amphetamine or marijuana, but also bitter-orange, alcohol, butane, chemotherapy drugs, over-the-counter medication and different antibiotics. Smoking is also a major risk factor for developing VA.t21 Thus, except for smoking, many of conventional atherosclerosis risk factors do not appear to be applicable to VA.t21 However, vasospastic angina can also occur without any triggering factor.

稀土离子的跨膜内流及Verapamil影响的研究

用放射性核素１４１Ｃｅ作示踪剂，通过对稀土Ｃｅ３＋在大鼠主动脉上的跨膜内流的研究表明，去甲肾上腺素（１．２μｍｏｌ／Ｌ）和ＫＣｌ（１００ｍｏｌ／Ｌ）都可引起Ｃｅ３＋跨膜内流量的增加，并以ＫＣｌ（１００ｍｏｌ／Ｌ）引起的增加量较多．钙拮抗剂Ｖｅｒａｐａｍｉｌ（１μｍｏｌ／Ｌ）对去甲肾上腺素（１．２μｍｏｌ／Ｌ）和ＫＣｌ（１００ｍｏｌ／Ｌ）引起的Ｃｅ３＋跨膜内流无明显的阻滞作用．

Verapamil modulating arsenic trioxide-induced QT interval prolongation in guinea pig

Objective To investigate therapeutic action of verapamil on QT prolongation induced by arsenic trioxide (As2O3) in guinea pig and to further explore its possible mechanism. Methods Different doses of As2O3 was infused intravenously to observe the changes of QT interval on the electrocardiogram (ECG) at different times in guinea pig.Patch clamp technique and laser scanning confocal microscopy were utilized to study the action of As2O3 on action potential duration (APD),L-type calcium current (ICa-L), rapid delayed rectifier potassium current (IKr) and intracellular calcium concentration ([Ca2+]i) of guinea pig myocytes. At the same time, verapamil was applied preliminarily to evaluate effects of verapamil on changes of the above index induced by AS2O3 . Results Intravenous administration of As2O3 at the dose of 1.6mg/kg and 0.8mg/kg prolonged QT interval on ECG obviously in guinea pig hearts dose dependently and time de pendently. QTc (corrected QT interval) was progressively prolonged in the 2-hour period of intravenous infusion of 1.6mg/ kg As2O3 from (328 .5±30.9)ms of control to (388 .4±31. 3)ms at 2h following As2O3 (P < 0.01). When verapamil was pretreated for 5min,then 1.6mg/kg As2O3 was added,the results showed that QTc was shorter in verapamil-treatment group (357 .3±21 .4)ms than that in As2O3 group (388 .4±31.3)ms (P<0.05) at 2h.Confocal experiments showed that in normal Tyrode solution, As2O3 (1μmol/L and 10/μmol/L) had no obvious effects on resting [Ca2+ ]i( P > 0 .05) in guinea pig cardiomyoeytes,however, 10μmol/L As2O3 could markedly enhance [Ca2+ ]. increase induced by KCl 60mmol/ L and the peak value increased from 903 .4±369.4 to 1674. 6±563 .2 ( P < 0.05 ) . The action of elevating [ Ca2+ ]i could be blocked by 10μmol/L verapamil incompletely. The patch-clamp studies indicated that As2O3 at concentration of 10μmol/L prolonged APD50 from (263 .6±75 .2)ms to (523.9±47 .8)ms (P<0.01) and APD90 from (277.5±77.5) ms to (536.3±49.6)ms (P<0.01),and increased ICa-L from ( -6.0±1.5)pA/pF to ( -8.7±2.0)pA/pF (P < 0.01) at 0mV and also reduced IKr from (6.7±1.8)pA/pF to (4.5±1 .8)pA/pF ( P < 0.05) .However,10μmol/L verapamil could modulate prolonging APD50 from (523 . 9±47 . 8 ) ms to (340.4±83 . 8 ) ms ( P < 0.01) and APD90 from (536.3±49.6) ms to (348.9±85.5)ms (P < 0.01) and correct increasing ICa-L induced by 10μmol/L As2O3 from ( - 8 .7±2.0) pA/pF to ( - 6.6±1.4) pA/pF ( P < 0.05) at 0mV. Conclusion As2O3 could induce prolongation of the QT interval on the ECG in guinea pig hearts and the ionic mechanism is associated with increasing ICa-L and inhibiting IKr/HERG. Verapamil may be useful in normalizing QT prolongation during As2O3 therapy by decreasing ICa-L and [Ca2+]i of ventricular myocytes in guinea pig.

Dose calcium channel blocker verapamil decrease urinary VMA levels in sympathoadrenal hyperactive patients with posttraumatic stress disorder?

Objective:The majority of the patients with posttraumatic stress disorders(PTSD) embrace augmented urinary flow of Vanillylmandelic Acid(VMA) than normal subjects owing to superior sympathetic doings,which steer to cardiovascular catastrophe.Urinary flow of VMA was evaluated as sympathoadrenal bustle marker in patients with posttraumatic stress disorder.Calcium ion shows a noteworthy dependability in nervousness owing to its special effects on brain synaptosomes.So this study was conducted to explore the effects of Verapamil on sympathoadrenal motion in patients with PTSD.Methods:Placebo controlled clinical tryout was conducted. At first hundred(100) PTSD patients were chosen and enrolled in the study,from department of Psychological Medicine Dow University of Health Sciences,Karachi.Verapamil 120 mg/day was specified in divided doses to group-Ⅰ(n=50)patients and group-Ⅱ(n =50) patients received placebo therapy on a daily basis for nine weeks.Each and every patient was monitored weekly,all the way through extent of study.Results:Underneath the posttraumatic stress disorder,urinary excretion of VMA was greater.Calcium channel blocker verapamil additionally abolished the embellished retort in urinary flow of VMA appreciably in patients with PTSD. Conclusion:Verapamil was experiential to be exceedingly effectual treatment.It reduces VMA levels in urine, and on the whole cardiovascular threat in PTSD patients.

Experimental study of verapamil on the relaxation of isolated human corpus cavernosum tissues

Aim： To evaluate the relaxant effect of verapamil on human corpus cavernosum in vitro and to assess the drug＇s potential as a treatment for erectile dysfunction （ED）. Methods： Preparations of the human corpus cavernosum were obtained from recently deceased young men who had had normal erectile function. The isometric tension and detailed curves were recorded when contractions induced by 10 mmol/L phenylephrine were reduced by different doses of verapamil or the vehicle control （sterile water）. The tension of human corpus cavernosum preparations are described as a percentage of their top tension before adding verapamil or the vehicle. ANOVA and least significant difference tests were used for statistical analysis. Results： Doses of 1μmol/L, 10 μmol/L and 100 μmol/L verapamil resulted in relaxation of （35.28 ± 7.96）%, （55.91 ± 6.41）%, （85.68 ± 4.16）% after 30 min, respectively. The vehicle control at the same time point produced relaxation of （-0.06 ± 10.57）% （P 〈 0.05）. Conclusion： Verapamil is significantly effective in relaxing normal human corpus cavernous smooth muscle induced by phenylephrine in vitro and the relaxant effect depends on the concentration of verapamil. （Asian J Androl 2006 Mar; 8： 195-198）