Effects of baclofen on reserpine-induced vacuous chewing movements in mice

We have described that GABA mimetic drugs present the ability to inhibit the expression of reserpine-induced oral movements. In this respect, oral movements is associated with important neuropathologies. This study investigates the effects of an acute or a repeated treatment of different doses of the GABA(B) agonist baclofen, as well as withdrawal from these treatments, on the development and/or expression of reserpine-induced vacuous chewing movements (VCM). Male mice received two injections of vehicle or of 1mg/kg reserpine separated by 48 h. In the first experiment, 24h later, animals were acutely treated with vehicle or baclofen (1, 2 or 4 mg/kg). In the second experiment, animals were treated with vehicle or baclofen (1 or 4 mg/kg) for four consecutive days receiving a concomitant injection of 1mg/kg reserpine (or vehicle) on Days 2 and 4. Twenty-four hours later, animals received vehicle or baclofen. Thirty minutes after the last injection, they were observed for quantification of VCM and open-field general activity. The acute administration of all the doses of baclofen abolished the manifestation of reserpine-induced VCM. Repeated treatment with 1mg/kg baclofen induced tolerance to the ability of an acute injection of this dose to reduce VCM. Treatment with baclofen (4 mg/kg) did not modify spontaneous VCM. Acute administration of the highest dose induced a decrease in general motor activity and a potentiation of the reserpine-induced decrease in general activity. These results reinforce the involvement of GABAergic hypofunction in the expression of oral movements and suggest that a repeated treatment with baclofen induces compensatory changes in GABAergic transmission that can attenuate its acute property to decrease VCM.     

Reserpine and breast cancer in women in Germany

Summary Exposure to reserpine was compared in 181 women interviewed prior to biopsy and found to have breast cancer and 307 women found to have a benign disorder of the breast. The age-adjusted relative risk of breast cancer in those who had taken reserpine was 0.6 (95% confidence limits: 0.4 and 1.1). When the 181 breast cancer patients were compared with a second control group of 101 women with a benign condition requiring surgery, the relative risk was 0.9 (95% confidence limits: 0.4 and 1.7). Neither long-term exposure nor its timing, gave any evidence of an association with breast cancer. The findings in this study do not support the hypothesis that rauwolfia derivatives initiate or promote breast cancer.This study was financially supported by the Ministery of Youth, Family and Health of the Fed. Rep. of Germany     

Decrease in rat striatal acetylcholine levels by some direct- and indirect-acting dopaminergic antagonists.

Several direct- or indirect-acting dopamine receptor antagonists were found to decrease rat striatal acetylcholine levels. The maximum decrease of about 50% was produced by pimozide (0.5 mg/kg), by haloperidol (0.5 mg/kg) and by reserpine (2.5 mg/kg). The decreases in acetylcholine produced by pimozide and by haloperidol were found to be specific for the striatum and did not alter diencephalonic, mesencephalonic, cerebellar or hemispheric acetylcholine levels. Furthermore, these two drugs completely blocked the increase in striatal acetylcholine produced by the dopamine receptor agonist, apomorphine, and had no effect on striatal choline acetyltransferase and cholinesterase. These data suggest that haloperidol and pimozide act on the striatal cholinergic neurons through strong blockade of dopamine receptors. Reserpine presumably decreased striatal acetylcholine levels indirectly by depleting biogenic amines. Clozapine and 1-fenfluramine were unable to block the action of apomorphine, as was shown previously for chlorpromazine. It is thus suggested that these drugs are reversible dopamine receptor antagonists. Their weaker action in decreasing striatal acetylcholine may depend upon this property.     

利血平治疗重型肠道病毒71型感染导致高血压患儿疗效观察

目的：探讨利血平辅助治疗EV71感染重症患儿所致高血压的疗效。方法：选择我院2010年4～6月均为EV71病毒阳性30例儿科住院患儿。将患儿随机分为对照组和治疗组,均应用甲泼尼龙、静脉注射用人免疫球蛋白、利巴韦林、米力农和其他常规性治疗,其中对照组15例未用利血平,治疗组15例加用利血平。利血平每次剂量0.07 mg/kg,每次最大量〈1.00 mg,血压降至正常后渐减量停用。结果：治疗12 h后,治疗组血压降至（100±10）mm Hg,对照组为（140±13）mm Hg,治疗组降压效果较对照组显著（t=3.71,P〈0.05）。结论：利血平可以辅助治疗EV71感染所致危重患儿病程中所出现的高血压,在降血压的同时可以耗竭患儿体内的儿茶酚胺,可以降低死亡率。     

利血平对多巴胺所致PC12细胞程序性死亡的影响

目的 :探讨帕金森病黑质多巴胺神经元的死亡机制。　方法 :用MTT法及流式细胞仪检测和观察囊泡单胺类转运体 (VMAT)抑制剂利血平对多巴胺所致的毒性作用和细胞程序性死亡的影响。　结果 :利血平 ( 10 0 0nmol/L)作用于大鼠嗜铬细胞瘤 (PC12 )细胞 96h ,对细胞无毒性效应 ;多巴胺 ( 0 .4mmol/L)作用于PC12细胞 4 8h即出现毒性效应 ;利血平 ( 10 0 0nmol/L)与多巴胺能够明显增强多巴胺 ( 0 .4mmol/L)的毒性效应 (P <0 .0 1) ,二者的协同毒性效应还具有时间依赖性。当多巴胺浓度 ( 0 .2mmol/L)较低时 ,协同毒性效应在药物作用 96h才显现出来。同时毒性效应主要是通过诱导细胞程序性死亡来实现的。　结论 :VMAT功能下降加重或触发多巴胺的内源性毒性 ,诱导多巴胺神经元的程序性死亡 ,可能参与帕金森病的发病机制。     

艾司西酞普兰与西酞普兰对利血平致抑郁障碍的疗效与安全性评价

目的探讨艾司西酞普兰与西酞普兰对利血平致抑郁障碍的疗效及安全性。方法选取2011年6月－2013年7月收治的利血平所致抑郁障碍60例患者作为研究对象,随机分为研究组和对照组,每组30例。研究组采用艾司西酞普兰系统治疗,每天10 mg口服;对照组采用西酞普兰系统治疗,每天20 mg口服。分别于治疗前、治疗第1、2、4、6周末进行汉密尔顿抑郁量表（HAMD）和不良反应量表（TESS）评定两组患者临床治疗情况。结果两组于治疗第2周末,HAMD评分均较治疗前有显著性下降（P〈0.05）;其中研究组在治疗第1、2周末HAMD评分下降均较对照组更为显著（P〈0.05）。而在治疗第4、6周末时两组间的HAMD评分及总有效率比较,差异无统计学意义（P〉0.05）。两组治疗后不良反应均较轻微,且多出现在用药初期,随着时间的延长可减轻或消失。两组不良反应发生率差异无统计学意义（P〉0.05）。结论艾司西酞普兰与西酞普兰均可有效改善利血平引起的抑郁症状,而艾司西酞普兰起效更快,治疗初期效果更显著,治疗依从性更高。     

LC-MS/MS检测降压类中药制剂中非法添加的9种化学药物

目的 建立快速、准确、灵敏的检测降压类中药制剂中非法添加盐酸肼屈嗪、阿替洛尔、氨苯蝶啶、卡托普利、盐酸哌唑嗪、盐酸普萘洛尔、氯沙坦钾、利血平和螺内酯等9种化学药物的LC-MS/MS方法.方法 采用KINETEX 2.6 C18 100A(50.0×2.10mm)色谱柱,梯度洗脱:流动相A为乙腈-甲醇(4∶1),流动相B为5mmol·L -1甲酸铵缓冲液(用甲酸调节pH至3.0),流速为0.3mL· min -1,检测波长为230、272nm,柱温为50℃;离子源为ESI源,雾化气压力为40psi,干燥气流速为12L·min -1,干燥气温度为325℃,毛细管电压为3.5kV,正离子检测模式.通过与对照品的色谱和质谱行为比较,对样品中是否添加该9种化学药物进行定性鉴别.结果 上述色谱-质谱条件下,9种化学药物的检出限为0.2～2ng,符合鉴别要求.结论 该方法的专属性较强、灵敏度较高,适用于降压类中药制剂中添加该9种化学药物的定性分析.     

The contribution of adrenergic mechanisms to frequency potentiation and to paired stimulation in guinea pig isolated atrial tissue

Summary In order to establish whether adrenergic mechanisms are involved in frequency induced potentiation and in the positive inotropic response to paired stimulation, the effect of adrenergic drugs on both processes were studied in guineapig isolated left auricles. 1. Owing to the positive inotropic effect of noradrenaline and isoproterenol the relative increase in contractile force at rising frequencies proved less pronounced than in control experiments, although the absolute maximal force that developed was higher in presence of the sympathomimetic drugs. 2. Pretreatment of the guinea-pigs with high doses of reserpine did not impair both potentiation phenomena in the isolated organs. Surprisingly, frequency potentiation proved even slightly increased in the noradrenaline-depleted organs. 3. A low concentration of propranolol (10^–9 M) did not affect both potentiation phenomena. Propranolol, in such concentration (10^–6 M) that unspecific, quinidine-like effects occurred diminished both frequency potentiation and the response to paired stimulation. 4. The results suggest that adrenergic mechanisms do not play any significant role in both potentiation phenomena.     

X线头部照射对利血平处理雄性大鼠神经内分泌的影响

本研究试图观察10 GyX线头部照射后48小时对利血平处理雄性大鼠神经内分泌功能的影响。实验设正常对照、利血平处理和利血平处理加照射三组。结果证实,利血平处理组(动物每隔12小时注射一次利血平,0.5mg/kg BW,共注射6次)与正常对照组比较,神经内分泌功能发生明显改变;而利血平处理加照射组与利盥平处理组比较,血清LH、FSH、TSH、GH、T_3、T_4和睾丸酮水平只趋于降低,血清PRL和皮质酮(P<0.05)有不同程度增高,但这些结果尚无正常大鼠经10 GyX线头部照射后变化明显。提示,用利血平处理雄性大鼠神经内分泌系统功能发生复杂的改变,不能出现正常大鼠头部照射后48小时下丘脑—垂体—靶腺系统功能变化。     

复方降压胶囊中利血平溶出度测定方法的研究

目的：建立复方降压胶囊中利血平的溶出度测定方法。方法：依照《中国药典》2000年版二部附录溶出度项下第三法，以正丙醇-0．1mol／L盐酸(3：7)为溶出介质，转速为75r／min，高效液相色谱法检测，检测波长为268nm。结果：在0．064～0．256μg／ml范围内(r=0．9997)，浓度与峰面积呈良好的线性关系，平均回收率为100．3％，RSD=0．52％。结论：该法操作简便、准确可靠。