一类创新药苯胺洛芬注射液安全性药理研究

目的:研究一类创新药苯胺洛芬的安全性药理,为新药研发提供依据。方法:通过小鼠自发活动试验、协调力实验和戊巴比妥钠催眠实验来考察苯胺洛芬对中枢神经系统的影响;通过麻醉Bealge犬实验考察苯胺洛芬对呼吸系统和循环系统的影响;通过正常大鼠和胃溃疡大鼠来考察苯胺洛芬对胃黏膜的影响。结果:苯胺洛芬剂量为临床拟用剂量的18倍时(小鼠216 mg.kg-1、大鼠162 mg.kg-1、犬45 mg.kg-1)单次给药后会导致麻醉Beagle犬血压一过性升高、小鼠自主活动降低、协调能力降低、与戊巴比妥钠具有协同作用;其余各剂量组和各观察指标均未见异常。结论:苯胺洛芬在剂量为临床拟用剂量的18倍时对中枢神经系统和心血管系统具有明显的影响;苯胺洛芬在剂量为临床拟用剂量的6倍时对中枢神经系统、呼吸系统和心血管系统未见明显影响;各剂量组对大鼠胃黏膜均未见明显影响。     

右旋布洛芬注射液安全药理学研究

目的 评价右旋布洛芬注射液对动物中枢神经系统、心血管系统及呼吸系统的影响。方法 通过小鼠自主活动试验、运动协调试验和戊巴比妥钠催眠/睡眠试验,考察右旋布洛芬注射液对中枢神经系统的影响;通过对清醒Beagle犬遥测心电图、血压和呼吸指标的检测,考察右旋布洛芬注射液对心血管系统和呼吸系统的影响。结果 右旋布洛芬注射液20、40、80 mg/kg剂量时对小鼠自主活动、爬杆行为均无显著影响,剂量为80 mg/kg时与戊巴比妥钠诱导的小鼠催眠/睡眠具有协同作用;剂量为10、20、40 mg/kg时对Beagle犬中枢神经系统、心血管系统和呼吸系统均没有显著影响。相同剂量条件下,右旋布洛芬注射液与布洛芬注射液比较,不良反应未见增加。结论 右旋布洛芬注射液对自主活动、运动协调能力、心血管系统和呼吸系统没有显著影响,大剂量时与戊巴比妥钠诱导小鼠催眠/睡眠有协同作用。     

去氢骆驼蓬碱衍生物DH-330的一般药理学研究

摘要：目的:研究1-（2-氯）苯基-9-丁基-β-咔啉（DH-330）在药效学剂量或之上时对实验动物神经系统、呼吸系统和心血管系统的影响,为其进一步的开发和使用提供安全性评价数据。方法:采用灌胃给药方式观察DH-330 (50,250,500 mg·kg-1)对小鼠自主活动、协调功能和阈下睡眠剂量戊巴比妥钠协同作用的影响;通过测定呼吸幅度、呼吸频率、动脉收缩压、动脉舒张压、动脉平均压观察DH-330对大鼠呼吸系统及心血管系统的影响。结果:DH-330剂量为药效学有效剂量的10倍时(小鼠500 mg·kg-1、大鼠350 mg·kg-1)单次给药后会导致小鼠自主活动减少,协调能力降低,对戊巴比妥钠催眠阈下剂量的效果无协同作用,但该剂量下会使麻醉大鼠血压降低及心电图异常,其余各剂量组和各观察指标均未见异常。结论:DH-330在有效量的10倍时可能会诱发中枢神经和心血管系统毒性。DH-330在有效剂量的10倍以下时,对动物中枢神经系统、呼吸系统和心血管系统均未见有毒理学意义的影响,因此在药效学有效剂量范围内具有较高的安全性。     

热淋清颗粒的一般药理学研究

目的观察热淋清颗粒对麻醉犬心血管系统、呼吸系统及小鼠神经系统的影响。方法十二指肠给予热淋清颗粒,记录戊巴比妥钠麻醉后杂种犬生理、心电图;观察热淋清颗粒对小鼠自发活动、机能协调功能和阈下戊巴比妥钠催眠作用的影响。结果十二指肠给药热淋清颗粒(15.43、7.72 g原生药/kg)对麻醉犬心血管系统和呼吸系统无明显影响;灌胃热淋清颗粒(114.3、57.2 g原生药/kg)在给药30 min时对小鼠的自由活动有一定的抑制作用,对小鼠的机能协调功能和与阈下戊巴比妥钠协同催眠作用均无显著影响。结论热淋清颗粒对麻醉犬心血管系统、呼吸系统及小鼠神经系统无明显影响。     

三升金丹胶囊的一般药理实验

目的：：观察三升金丹胶囊的一般药理作用,为临床用药和安全用药提供信息。方法：采用一般行为观察实验、戊巴比妥钠阈下催眠实验、自发活动实验、转棒实验考察供试品对小鼠中枢神经系统的影响,三升金丹胶囊低中高剂量分别为90,180,360 mg·kg-1;通过检测麻醉状态下Beagle犬的血压、心电及呼吸参数来考察供试品对犬心血管系统及呼吸系统的影响,三升金丹胶囊低中高剂量分别为16,32,64 mg·kg-1。结果：小鼠给予供试品后无异常行为出现、供试品与戊巴比当钠无协同催眠作用、供试品对小鼠的自发活动及机体的协调能力没有影响(P>0.05),对麻醉状态下Beagle犬的血压、心电及呼吸也无明显影响(P>0.05)。结论：在所设计的剂量水平下,三升金丹胶囊对小鼠中枢神经系统、对犬呼吸系统和心血管系统无明显影响。     

苦苣菜药材细粉混悬液安全药理学研究

目的通过研究苦苣菜药材细粉混悬液对ICR小鼠、SD大鼠中枢神经系统和Beagle犬心血管系统的影响,观察药物潜在的对生理功能的不良影响,为临床实验提供依据及参考。方法 ICR小鼠单次灌胃给予苦苣菜细粉混悬液,进行小鼠自主活动和协同睡眠实验;SD大鼠单次灌胃给予苦苣菜细粉混悬液,进行大鼠转棒实验,评价苦苣菜对大、小鼠中枢神经系统的影响。Beagle犬单次灌胃给予苦苣菜细粉混悬液,采用DSI大动物生理信号遥测系统检测清醒Beagle犬心电、血压和体温,评价苦苣菜对Beagle犬心血管系统的影响。结果与溶媒对照组比较,单次灌胃给予苦苣菜细粉混悬液,大、小鼠各剂量组自主活动未见明显变化、未见与阈下剂量戊巴比妥钠协同睡眠作用、平衡运动能力未见明显影响;与溶媒对照组比较,Beagle犬单次灌胃给予苦苣菜细粉混悬液,各剂量组动物未见药物相关的心电、血压和体温指标的明显变化。结论本实验条件下,单次灌胃给予苦苣菜细粉混悬液对实验动物心血管系统和中枢神经系统无明显影响。     

对羟基苯甲酸钠的安全药理学研究

目的 观察对羟基苯甲酸钠对实验动物中枢神经系统和心血管系统的影响。方法 昆明小鼠单次灌胃给予20,50,100 mg·kg^-1对羟基苯甲酸钠溶液,通过小鼠甩尾试验、自主活动试验、爬杆试验、协调睡眠试验和Morris水迷宫试验,考察对羟基苯甲酸钠对中枢神经系统的影响。SD大鼠单次灌胃给予14,35,70 mg·kg^-1对羟基苯甲酸钠溶液,Beagle犬单次灌胃给予4.2,10.5,21 mg·kg^-1对羟基苯甲酸钠溶液,通过检测Beagle犬血压和体温以及SD大鼠的心电,考察对羟基苯甲酸钠对心血管系统和体温的影响。结果 对羟基苯甲酸钠对小鼠感觉-运动反射、自主活动行为、协调功能、戊巴比妥钠阈下睡眠剂量小鼠入睡率和学习记忆能力无明显影响;对Beagle犬血压、体温以及SD大鼠心电均无明显影响。结论 本实验条件下,单次灌胃给予对羟基苯甲酸钠溶液对实验动物中枢神经系统和心血管系统无明显影响。     

亚硫酸氢钠穿心莲内酯的一般药埋学研究

目的观察亚硫酸氢钠穿心莲内酯对动物的一般药理作用。方法用抖笼法、爬杆法、游泳耗竭法及麻醉家犬静脉滴注等方法,观察亚硫酸氢钠穿心莲内酯对动物中枢神经系统、心血管及呼吸系统的影响。结果给小鼠静脉推注亚硫酸氢钠穿心莲内酯250、500mg/kg后,小鼠的自发活动明显减少。爬杆试验等级数和游泳耗竭时间与对照组比较无明显差异。小鼠静脉推注亚硫酸氢钠穿心莲内酯后加腹腔注射戊巴比妥钠(40mg/kg),500mg/kg组可缩短戊巴比妥钠入睡时间,250、500mg/kg组可延长睡眠持续时间。麻醉家犬静脉滴注亚硫酸氢钠穿心莲内酯后,对血压、心率、心律及心电图各波形未见有临床意义的改变,呼吸频率和深度也未见明显影响。结论亚硫酸氢钠穿心莲内酯对小鼠中枢神经系统具有明显的镇静作用,对小鼠的协调运动无明显影响,与戊巴比妥钠催眠作用有协同作用,麻醉家犬静脉滴注亚硫酸氢钠穿心莲内酯对心血管及呼吸系统均无明显影响。     

沙棘提取物一般药理学实验研究

目的:为探讨沙棘提取物的安全性,观察沙棘提取物的一般药理作用,以供临床用药参考。方法:观察沙棘提取物对家犬血压、呼吸频率、呼吸振幅和心电图标准Ⅱ导联的影响,对小鼠自发活动的影响,对戊巴比妥钠阈剂量致小鼠睡眠时间的影响,对戊巴比妥钠阈下剂量致小鼠催眠有无明显协同作用,对小鼠的转棒运动有无明显的影响。结果:沙棘提取物在155 mg(原料药).kg~(-1)体重给药剂量内,对家犬心血管系统和呼吸系统均无明显影响;在754mg(原料药).kg~(-1)体重给药剂量范围内,对小鼠的中枢神经系统没有明显的抑制作用,对小鼠的机能协调运动也无明显影响。结论:一般药理作用研究表明,在上述剂量内沙棘提取物对动物心血管系统、呼吸系统及中枢神经系统均无明显影响,提示其不良反应小。     

金丝桃苷的一般药理学研究

目的 观察金丝桃苷对实验动物中枢神经系统、呼吸系统、心血管系统的影响。方法 以低、中、高剂量(12.5、60.0、300.0 mg/kg)金丝桃苷ig给予BALB/c小鼠,观察小鼠的一般行为、自主活动、入睡只数、入睡时间和协调运动,考察其对小鼠中枢神经系统的影响;以低、中、高剂量(2、12、65 mg/kg)金丝桃苷对麻醉Beagle犬十二指肠给药,观察给药前后麻醉犬的呼吸频率、呼吸幅度、收缩压(SBP)、舒张压(DBP)、平均血压(MBP)、心率(HR)、Ⅱ导联心电图QT间期、QRS波群时间、PR间期、ST段偏移幅度等相关指标的变化,考察其对Beagle犬呼吸系统及心血管系统的影响。结果 与对照组比较,用药后各组小鼠中枢神经系统,Beagle犬呼吸幅度、呼吸频率、血压、心率、心电图均无明显变化。结论 金丝桃苷对小鼠中枢神经系统、Beagle犬呼吸系统及心血管系统均无明显影响,提示其不良反应小。     

Fibrin glue: a review of its preparation, efficacy, and adverse effects as a topical hemostat

Fibrin glue is composed of two separate solutions of fibrinogen and thrombin. When mixed together, these agents mimic the last stages of the clotting cascade to form a fibrin clot. Fibrin glue is available in Europe but is not commercially available in the U.S.; therefore, investigators have extemporaneously compounded their own fibrin glue. Fibrinogen can be obtained from pooled, single-donor, and autologous blood donors and is usually isolated by the process of cryoprecipitation. The thrombin component is generally derived from commercial bovine sources. Some investigators have added calcium chloride and/or antifibrinolytics (i.e., aminocaproic acid, aprotinin) to their preparations. Fibrin glue can be applied using a double-barrel syringe or by spray application. Although fibrin glue has been used in a variety of surgical procedures, it has been especially useful in heparinized patients undergoing cardiovascular procedures requiring extracorporeal circulation, as it does not require an intact hemostatic system to be effective. Fibrin glue also has been evaluated in presealing woven or knitted Dacron vascular grafts. The major drawback to its use is the risk of transmitted serological disease from pooled and single-donor blood donors. The safest preparations use the patient's own blood to prepare fibrin glue. Overall, fibrin glue is a useful adjunct to other methods to control bleeding in selected surgical patients.     

Effects of Inhaled Rosemary Oil on Subjective Feelings and Activities of the Nervous System

Rosemary oil is one of the more famous essential oils widely used in aroma-therapy. However, the effects of rosemary oil on the human body, in particular the nervous system, have not been sufficiently studied. This study investigates the effects of the inhalation of rosemary oil on test subjects’ feelings, as well as its effects on various physiological parameters of the nervous system. Twenty healthy volunteers participated in the experiment. All subjects underwent autonomic nervous system (ANS) recording. This consisted of measurements of skin temperature; heart rate; respiratory rate; blood pressure; evaluations of the subjects’ mood states; and electroencephalography (EEG) recordings in the pre-, during treatment, and post-rosemary inhalation periods as compared with control conditions. Our results showed significant increases in blood pressure, heart rate, and respiratory rate after rosemary oil inhalation. After the inhalation treatments, subjects were found to have become more active and stated that they felt “fresher”. The analysis of EEGs showed a reduction in the power of alpha1 (8–10.99 Hz) and alpha2 (11–12.99 Hz) waves. Moreover, an increment in the beta wave (13–30 Hz) power was observed in the anterior region of the brain. These results confirm the stimulatory effects of rosemary oil and provide supporting evidence that brain wave activity, autonomic nervous system activity, as well as mood states are all affected by the inhalation of the rosemary oil.     

欧前胡素急性毒性和安全药理学研究

目的观察欧前胡素对大、小鼠的急性毒性,以及对小鼠神经系统和犬心血管系统、呼吸系统的影响。方法通过腹腔内注射给药（ip）和灌胃给药（培）研究欧前胡素对小鼠的急性毒性,以及培对大鼠的急性毒性实验。安全药理学实验中以50、100、200mg／kg分别单次培给予小鼠欧前胡素,观察对小鼠神经系统的影响（包括小鼠自发活动、爬杆能力、小鼠阈下剂量戊巴比妥钠催眠协同实验）;以25、50、100mg／kg分别单次口服给药（po）欧前胡素,观察对犬心血管系统和呼吸系统的影响（包括心电图、血压、心率,以及呼吸频率、幅度、节律等指标）。结果欧前胡素培对小鼠的LD50为988．5mg/kg;ip对小鼠的LD50为603．3mg／kg;ig对大鼠的LD50为3188．7mg／kg。欧前胡素单次ig对小鼠神经系统无明显影响;单次po对犬心血管系统指标和呼吸系统指标无明显影响。结论欧前胡素安全范围较大,毒性较容易控制,且对正常动物（包括小鼠、大鼠和犬）的降压作用不显著,因此具有较大的临床应用可能性。     

General pharmacological studies on N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate. 3rd communication: effect on cardiovascular system

In this general pharmacological study of N-[2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), its effects on the cardiovascular and respiratory systems were studied. SUN 1165, at doses of up to 1.0 mg/kg i.v., had almost no effect. SUN 1165, at doses of 3.0 and 6.0 mg/kg i.v., caused dose-dependent decreases in blood pressure, common carotid, vertebral, coronary, hepatic and femoral artery and portal vein blood flows, cardiac contractility, heart rate and myocardial oxygen consumption. SUN 1165 increased urine volume and urinary excretion of electrolytes in rats at a dose of 100 mg/kg p.o. SUN 1165 decreased renal plasma flow and urinary excretion of electrolytes in anesthetized dogs at 6.0 mg/kg i.v., but at the antiarrhythmic doses (1.0-3.0 mg/kg i.v. in dogs), it had almost no effects on renal function. SUN 1165 had almost no effect on the autonomic nervous systems in anesthetized dogs. These results suggest that SUN 1165 at the antiarrhythmic doses do not have any effects on the respiratory and cardiovascular systems, renal function and autonomic nervous systems in rats and dogs, but that when administered at high doses, it has inhibitory effects on respiratory and cardiovascular system and renal function. In conclusion, SUN 1165 seems to be a novel antiarrhythmic drug relatively free of cardiovascular, respiratory, renal and autonomic effects.     

General pharmacological properties of the new proton pump inhibitor (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulf inyl]- 1H-imidazo[4,5-b]pyridine.

The general pharmacological profiles of a novel proton pump inhibitor, (+/-)-5-methoxy-2-[[(4-methoxy-3,5-dimethylpyrid-2-yl)methyl]sulfi nyl]- 1H-imidazo[4,5-b]pyridine, TU-199) on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions were investigated. TU-199 had no effects on general signs and behavior in mice. TU-199 (300 mg/kg p.o.) decreased locomotor activity 3 h after administration in mice. TU-199 had no effect on pentobarbital-induced hypnosis, analgesic activity and electroshock-induced convulsion in mice, and on rectal temperature in rats. However, TU-199 (300 mg/kg p.o.) showed slight anticonvulsant activity on pentylenetetrazole-induced convulsion in mice. TU-199 had no effect on respiratory rate, blood pressure, heart rate, femoral blood flow and electrocardiogram in anesthetized dogs. TU-199 (10(4) M) caused the cumulative concentration-response curve obtained with acetylcholine in isolated guinea pig ileum to shift to the right. However, TU-199 showed no effect on contraction of isolated guinea pig ileum and had no effect on intestinal motility in mice, gastric emptying in rats, bile secretion in rats and carbachol-induced salivary secretion in mice. TU-199 had no effect on urinary volume and excretion of electrolytes in rats. These results suggest that TU-199 does not induce serious adverse effects on the central nervous system, cardiorespiratory system, autonomic nervous system, gastrointestinal system and renal functions with the exception of a decrease in spontaneous motor activity with high doses.     

冠心宁注射液安全药理学研究

目的 观察冠心宁注射液对中枢神经系统、心血管系统和呼吸系统的影响,为临床用药提供参考。方法 采用遥测技术,研究冠心宁注射液对清醒Beagle犬血压和心电的影响;采用全身体积描记系统,研究冠心宁注射液对SD大鼠呼吸系统的影响;采用小鼠自主活动、协调运动和阈下剂量戊巴比妥钠催眠试验,研究冠心宁注射液对中枢神经系统的影响。结果 遥测试验结果显示,与溶媒对照组比较,注射用冠心宁1、2、4 mL·kg^-1三个剂量组Beagle犬给药后30 min内心率减慢,血压下降,30 min后逐渐恢复,其他心电指标无明显变化。大鼠呼吸试验结果显示,与溶媒对照组比较,冠心宁注射液4、8、16 mL·kg^-1剂量组大鼠呼吸频率、潮气量和每分通气量无明显差异。小鼠中枢神经系统试验结果显示,与溶媒对照组比较,冠心宁注射液5、10、20 mL·kg^-1剂量组小鼠药后15 min和30 min自主活动次数降低;而协调运动等级和睡眠率无明显差异。结论 冠心宁注射液可短暂降低动物血压和心率,抑制自主活动,对呼吸系统无明显影响。     

General pharmacological action of tritoqualine (TRQ; (+/-)-(R*)-7-amino-4, 5, 6-triethoxy-3-[(R*)-5, 6, 7, 8-tetrahydro-4-methoxy-6-methyl-1, 3-dioxolo [4, 5-g] isoquinolin-5-yl] phthalide

The general pharmacological action of TRQ was investigated, and the following results were obtained: With regard to its influence on the central nervous system, TRQ moderately potentiated the actions of hexobarbital (sleeping time) and methamphetamine (stereotyped behavior) at doses above 100 mg/kg, p.o. TRQ, however, had little influence on behavioral changes, EEG and motor function. TRQ only had slight influence on the respiratory and cardiovascular system at doses ranging from 0.1 to 3 mg/kg, i.v. Significant decrease in SBP and increases of HR, FAF and respiratory rate were observed after high doses (10-30 mg/kg, i.v.) of TRQ. TRQ also had little influence on contractility and pacemaker in isolated hearts, but moderately increased the coronary flow. The inhibitory effect of TRQ on the isolated smooth muscle was observed at high concentration and was non-specific. Furthermore, TRQ exhibited little influence on the autonomic nervous system. Among the effects of TRQ on the gastrointestinal system, it was shown that TRQ moderately increased the outflow of bile after doses above 1 mg/kg, i.v. TRQ also showed no remarkable actions on other aspects of the gastrointestinal system and blood coagulation system. Considering the present results, it may be suggested that there should be no serious problems in the application of TRQ as a hepatoprotective agent.