The Protective Effect of Nimodipine,a Calcium Antagonist,and Its Influence on Soman Clearance in the Anaesthetized Rabbit

Abstract— The effect of pretreatment with a vasoactive compound, nimodipine, on soman intoxication in peripheral organs of rabbits was studied by measuring changes in the cholinesterase and acetylcholinesterase activity and by measuring clearance of soman in blood using gas chromatography/high resolution mass spectrometry. In animals receiving soman only, initial blood concentrations were approximately 100 ng mL^?1 and were still detectable after 5 min. The clearance rate of soman in blood markedly increased following nimodipine pretreatment such that soman was below the detection limit (0·002–0·003 ng mL^?1) in all samples. Soman injection caused a significant inhibition of the acetylcholinesterase activity in serum, and in brain. In rabbits pretreated with nimodipine, no significant inhibition of acetylcholinesterase activity occurred after soman injection. In view of the effects of nimodipine on soman clearance and on the acetylcholinesterase and cholinesterase inhibition during soman intoxication, we suggest that nimodipine has profound circulatory effects, which during soman intoxication, increase the vascular perfusion through the body and thereby increase the detoxifying capacity.     

钙离子拮抗剂尼莫地平治疗过敏性紫癜的临床初探

过敏性紫癜是多发于男性少儿的血管性疾病，可累及皮肤、胃肠和肾脏，出现相应的临床症状，临床上常给予抗组胺、安络血等治疗，而对于关节型、胃肠型和肾型过敏性紫癜则给予皮质类固醇治疗，但疗效欠佳。笔者探索采用钙离子拮抗剂尼莫地平协同治疗过敏性紫癜。     

The Effects of some Anticholinergic Compounds on the Infused Urinary Bladder of Anaesthetized Rabbits

Abstract The intravesical pressure and volume of the urinary bladder of anaesthetized rabbits were studied using a urinary bladder infusion technique. It was shown that the anticholinergic compounds used, atropine, emeprone, and PR 197, significantly increased the urinary bladder volume capacity, and that they decreased the micturition pressure. Atropine was the most potent compound in increasing the bladder volume capacity, followed by PR 197 and emeprone, mentioned in order of potency. Atropine and PR 197 increased the bladder volume capacity and the micturition threshold pressure significantly more than emeprone. There was no statistically significant difference between the effects of the different compounds on the residual volume or the micturition pressure. It is suggested that the effects of the compounds are confined mainly to the bladder and most probably to its cholinergic structures.     

家兔灌服磷化铝中毒的解毒方法研究

目的遴选具有阻止磷化氢生成的解毒型洗胃剂,寻找口服磷化铝中毒早期治疗的最佳方案。方法将48只家兔分为6组,分别灌服最低全数致死量的磷化铝,即刻再分别灌服1%硫酸铜、0.02%高锰酸钾、食用油、液体石蜡或持续进行胃肠减压,并分别于灌磷化铝粉前、灌磷化铝粉后0.5 h及死亡时抽取家兔动脉血2 mL进行血气分析,并记录家兔死亡时间。结果灌食用油洗胃组平均生存时间为(105.25±23.38)min,持续胃肠减压组平均生存时间为(4 200±63.22)min,均明显长于其他组(P<0.05或P<0.01)。结论口服磷化铝中毒后给予食用油洗胃以及持续进行胃肠减压,是提高解救存活率的关键。     

钙拮抗剂桂利嗪的合成

桂利嗪(1,曾名为脑益嗪),化学名1-二苯甲基-4-反式肉桂基哌嗪,是钙拮抗剂类周围血管扩张药,其合成已有多篇文献报道[1～4]。通过综合分析,设计了如下合成路线:收稿日期:2000-04-17作者简介:王国喜(1966),男,讲师,主要从事有机合成教学及科研。Tel:0372-3948618E-mail:guoxiw@371.net　　利用三聚甲醛代替甲醛溶液,使反式肉桂基氯(2)收率提高;同时用二苯甲烷直接进行溴化制得高收率的二苯溴甲烷。1的制备,以PEG400为相转移催化剂,无水碳酸钾为束酸剂,使收率提高到76.3%(文献[1]:55.3%)。本路线收率高,生产成本显著降低,所得产品符合中国药…     

心理疗法在戒毒者康复中的作用

目的:探讨强制戒毒所心理疗法对戒毒者的康复效果.方法:对30例戒毒者进行为期3个月的心理疗法(治疗组),与未使用心理疗法的30例戒毒者(对照组)比较,采用自制的社会功能康复治疗表和社会功能缺陷筛选量表(SDSS)进行效果评定.结果:治疗组经心理治疗后社会功能缺陷均分明显降低(P均＜0.01).两组学员治疗后社会功能各因子分均有显著改善,而且治疗组优于对照组(P均＜0.01).结论:心理疗法有助于戒毒者社会功能的恢复.     

麻醉开胸犬静脉注射EMD56431血液动力学研究

目的:研究ATP敏感钾通道开放剂EMD56431对麻醉开胸犬血流动力学的作用.方法:采用静注(i.v.)给药方式,动态监测麻醉开胸犬左心室收缩压(LVSP)、左室压上升和下降速率(±dp/dtmax),左室舒张末期压(LVEDP)、收缩压(SAP)、舒张压(DAP)、平均动脉压(MAP)、ECG等指标,并计算出心率(HR)、心脏指数(CI)和外周阻力(TPR).结果:静注EMD56431在一定范围内可使麻醉开胸犬呈时间和剂量依赖性的血压降低,尤以DAP下降为甚,在降压的同时,可见HR减慢.除大剂量EMD56431外,其余各剂量对心脏泵功能、血流量、ECG均无明显影响.结论:EMMD56431可显著降低血压,改善心脏供血.     

Atropine and Oxime Treatment in Lethal Soman Poisoning of Anaesthetized Guinea-pigs: HLö 7 Dimethanesulfonate Versus HI 6 Dichloride

Abstract: The oxime HI 6 is considered to be effective in soman poisoning and less effective in tabun poisoning. Recently, HLö 7 was shown to reactivate acetylcholinesterase (AChE) inhibited by soman and tabun. Therefore, the efficacy of HLö 7 and HI 6 was compared in soman poisoned guinea-pigs. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the a. carotis, v. jugularis and trachea were cannulated. After base line measurements soman 0.08 mg/kg (= 5 x LD50) or 0.16 mg/kg (= 10 x LD50) was injected intravenously, 2 min. later the antidotes were applied intravenously: HLö 7 0.03 or 0.1 mmol/kg, HI 6 0.03 or 0.1 mmol/kg, atropine 10 mg/kg, or a combination of atropine and an oxime. Respiratory and circulatory parameters were recorded for 60 min. or until the death of the animal. The injection of 5 x LD50 soman resulted in a rapid respiratory arrest followed by circulatory failure in the soman and soman plus oxime groups (survival time about 7 min). Atropine restored the circulatory parameters to base line but was unable to provide a sufficient respiratory function (survival time 26 min.). The combination therapy with atropine plus HLö 7 or HI 6 improved the respiration sufficiently, restored the circulation completely, and prolonged the survival time to about 50 min. Atropine treatment was insufficient in animals poisoned with 10 x LD50 soman. The combination of atropine and HLö 7 or HI 6 improved respiration, circulation, and survival time to various extent. Despite of the striking therapeutic effect no reactivation of erythrocyte AChE by the antidotes was observed. These results indicate, that the therapy with oximes or atropine alone is insufficient. The treatment with atropine plus HLö 7 or HI 6 proved to be efficient. HLö 7 is considered to be at least as effective as HI 6 in soman poisoning in this guinea-pig model.     

Relationship between Plasma Concentration and Antihypertensive Effect of the Dihydropyridine Calcium Antagonist,Benidipine, in Rats

Although benidipine hydrochloride, a hydrophobic and weakly cationic dihydropyridine calcium antagonist, has slow onset but long-lasting anti-hypertensive effect in experimental animals and man, after administration it rapidly disappears from the plasma. Correlation of the plasma concentration with reduction in blood pressure has been investigated in spontaneously hypertensive rats, and concentrations in the mesenteric artery were compared with those in plasma after oral and intravenous administration of benidipine to rats. After oral administration of benidipine to spontaneously hypertensive rats, the fall in blood pressure showed an anti-clock hysteresis phenomenon. Using concomitant analysis, plasma concentrations and anti-hypertensive activity could both be closely fitted to a one-compartment open model and the effect compartment for the pharmacological activity of benidipine could be described by a Hill equation. Concentrations in the mesenteric artery increased rapidly and then declined more slowly than in plasma. The mean residence time of benidipine in the mesenteric artery corresponded closely to the reciprocal of the rate constant for elimination of benidipine from the effect compartment. From these results it seems that benidipine is retained longer in the plasma membrane, an effective site, because of its physicochemical properties, and thus shows a more sustained anti-hypertensive effect than would be predicted from its disposition in plasma.     

浅谈尼莫地平治疗高血压脑出血患者的临床效果

目的:探讨尼莫地平治疗高血压脑出血患者的临床效果。方法:选取2013年7月~2014年7月在院住院或就诊的80例高血压脑出血患者作为研究对象,并分为实验组和对照组各40例,其中对照组给予常规治疗,实验组在常规药物的基础上给予尼莫地平治疗。结果:两组患者经过一个疗程的用药治疗后,实验组显效21例,有效17例,总有效率为95.00%;对照组显效13例,有效15例,总有效率70.00%。两组患者神经功能缺损评分和血肿量情况比较有显著差异(P0.05)。结论:尼莫地平治疗高血压脑出血总有效率高。     

Convulsive Effect of Theophylline in Conscious and Anaesthetized Guinea-pigs

Abstract: In urethane-anaesthetized guinea-pigs, the effect of theophylline (theo) on heart rate, arterial blood pressure, respiration rate and limb movements were recorded. Continuous intravenous infusion of theo initially increased the respiratory and heart rates and lowered the arterial blood pressure. After infusion of about 50 mg/kg of theo, the cardiovascular effects reached a maximum and were then only slightly changed until the terminal stage. A tonic stretching of the limbs (at 155 ± 15 mg/kg) preceded generalized seizures of clonic tonic convulsions which were recorded after infusion of 367 ± 25 mg/kg of theo. At this stage, respiration was highly irregular. PaO₂ started to fall and PaCO₂ to rise, while a plasma acidosis developed rapidly. The convulsions progressed in frequency and intensity and were terminally associated with respiratory and cardiovascular collapse. The convulsive effects of theophylline were similar to those observed in conscious guinea-pigs after 250 mg/kg of theo orally. The present findings agree with the view that the convulsive effect is a primary life-threatening action of theophylline. The method described may be of use in the search for new, less toxic xanthine drugs.     

Public Policy Statement on Opioid Antagonist Agent Detoxification Under Sedation or Anesthesia (Oadusa)

Abstract

The success of opioid agonist maintenance has stimulated efforts to make this form of treatment more available. Methadone medical maintenance, coordination of methadone services from a physician's office, has been offered as an alternative to narcotic treatment programs for stable, recovered and socially rehabilitated opioid dependent patients. Despite the successful implementation of methadone medical maintenance programs, a number of important questions regarding the appropriate guidelines for the use of this model of care remain. The current paper reviews the process and outcome of the Medical Maintenance Consensus Panel, which was convened for the federal Center for Substance Abuse Treatment. We outline the process and describe the two guidelines that were produced by this process that are targeted at physicians, narcotic treatment programs, and policy makers.     

速激肽受体拮抗剂在哮喘治疗中的作用

综述有关速激肽受体拮抗剂对哮喘的治疗作用研究进展。速激肽是一类存在于感觉神经的活性肽，目前已发现的速激肽包括P物质、神经肽A、神经肽B、神经肽K和神经肽γ。研究表明，速激肽与哮喘的关系密切，其受体拮抗剂可用于哮喘的防治。     

Effect of the H2-Receptor Antagonist Cimetidine,on the Pharmacokinetics and Pharmacodynamics of the H1-Receptor Antagonists Hydroxyzine and Cetirizine in Rabbits

The effects of coadministration of the H₂-receptor antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H₁ receptor antagonists hydroxyzine and cetirizine were studied in rabbits. A single dose of hydroxyzine, 10 mg (Experiment A), or cetirizine, 10 mg (Experiment B), was given intravenously on three occasions: 2 weeks before cimetidine administration, after cimetidine, 100 mg/kg, had been given every 12 hr for 1 week, and 2 weeks after the cimetidine was discontinued. Serum concentrations of hydroxyzine and cetirizine, the active metabolite of hydroxyzine arising in vivo (Experiment A), or cetirizine (Experiment B) were measured by HPLC. The pharmacologic effects of hydroxyzine and cetirizine were monitored by measuring the suppression of histamine-induced wheals, using an IBM-PC and digitizer. The hydroxyzine and cetrizine half-life and AUG₀ values were significantly increased and the systemic clearance rates were significantly decreased in the presence of cimetidine. Similar results were obtained when cetirizine was administered de novo. Wheal suppression produced by hydroxyzine or cetirizine was increased and prolonged in the presence of cimetidine. The synergism observed between hydroxyzine or cetirizine and cimetidine in suppression of the histamine-induced cutaneous response may be due to a pharmacokinetic interaction.     

纳洛酮对敌敌畏中毒家兔血浆β-内啡肽含量的影响

目的 研究纳洛酮对敌敌畏中毒家兔血浆β-内啡肽含量的影响.方法 将家免分为两组,均采用敌敌畏灌胃法使其中毒,常规治疗组予硫酸阿托品和碘解磷定治疗,纳洛酮预防组在中毒前予纳洛酮,中毒后予硫酸阿托品和碘解磷定治疗,分别测定两组动物敌敌畏中毒前和中毒治疗后不同时间血浆β-内啡肽含量.结果 与正常动物相比,常规治疗组血浆β-内啡肽水平在中毒治疗后1～20 h均显著升高(P<0.001);与常规治疗组相比,纳洛酮预防组血浆β-内啡肽水平在中毒治疗后1～20 h均显著降低(P<0.01).结论 家兔急性敌敌畏中毒可引起血浆β-内啡肤水平急剧升高,纳洛酮预防性应用则可明显降低中毒家兔血浆β-内啡肽水平.     

山蒟提取物对兔动脉粥样硬化的影响

目的:观察山蒟提取物对高脂喂养家兔动脉粥样硬化的影响,并初步探讨其作用机制。方法:将家兔随机分为高脂组和山蒟(高、低剂量)组,高脂食物饲养3wk后给予药物或生理盐水,12wk周后考察并测定其血脂、主动脉病变程度、冠状动脉病变情况、血清总超氧化物歧化酶(SOD)和丙二醛(MDA)活性,并设对照组。结果:与高脂组比较,山蒟高剂量组血胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL)显著降低(P<0.05),高、低剂量组主动脉及冠状动脉病变程度显著降低(P<0.05),血清SOD活性升高,血清MDA活性降低(P<0.05)。结论:山蒟提取物能够明显降低兔动脉粥样硬化病理病变程度,具有良好的抗氧化能力,并且对血脂具有一定的调节作用。     

壳聚糖对尼莫地平的控释作用

研究不同脱乙酸度的壳聚精对尼莫地平（nimodiPin,ND）释放性能的影响。结果表明,壳聚精是一种很好的药物辅料,它对ND具有一定的援释作用,其脱乙酸度越高,缓释作用越强。     

氟桂利嗪与尼莫地平治疗偏头痛疗效对比

目的：对氟桂利嗪与尼莫地平治疗偏头痛进行疗效对比。方法：将101例偏头痛患者,随机分为治疗组51例,用氟桂利嗪5mg,bid;对照组50例,用尼莫地平30mg,tid。评价服药后头痛情况,并选取有效病例针对症状控制所需时间再次进行对比。结果：氟桂利嗪与尼莫地平治疗偏头痛有效率分别为82．4％和80．0％,治疗组用药后2周内头痛控制率40．5％,高于对照组15．0％,结论：氟桂利嗪治疗偏头痛起效快,能迅速减轻症状,并减轻患者的经济负担。     

Concentration of Tricyclic Antidepressants in Plasma,Heart and Skeletal Muscle after their Intravenous Infusion to Anaesthetized Rabbits

Abstract: In order to compare the toxic concentrations of four different tricyclic antidepressants in the heart and plasma, 5 mg/kg of amitriptyline, doxepin, nortriptyline or protriptyline were infused intravenously over 5 min. into anaesthetized rabbits. The concentrations of the antidepressants five minutes after the termination of the infusion were measured by gas chromatography in the plasma, heart ventricles, and femoral muscle. On average, the concentrations in the heart were 40 to 200 times higher than those measured in plasma, the concentration of protriptyline being highest. The heart/plasma concentration ratios were higher for protriptyline and amitriptyline than for nortriptyline and doxepin. The toxicity of the antidepressants correlated neither to their heart concentrations nor to their heart/plasma concentration ratios. It seems that the different acute cardiotoxicity of tricyclic antidepressants cannot be explained by their different concentrations in the plasma or in the heart muscle only, but they seem to have different toxic potencies.