青藤碱的药理作用 Ⅱ.毒性及一般药理

青藤碱(sinomenine)对小白鼠口服半数致死量为580±51毫克/公斤;大白鼠一次口服694毫克/公斤无不良反应;犬及猴分别口服45及95毫克/公斤有显著镇静作用及轻度胃肠反应;但静脉给药于犬及猴(5—13.5毫克/公斤)立即出现高度衰弱、血压下降、心率增速、呼吸困难,此种严重反应于一小时许恢复(猴);犬及猴无论口服或静脉给药后,肝、肾功能均无变化;大白鼠亚急性毒性试验表明,该药40及80毫克/公斤/日腹腔注射,连续二周,对动物体重、食欲、血象、内脏病理切片均无明显改变.青藤碱静脉给药可使麻醉兔、犬的血压显著降低,剂量愈大,作用愈显著,其降压作用与M-胆碱反应系统无关,亦无直接扩张血管作用;高浓度抑制离体蛙心的收缩,此外,该药抑制离体肠肌,并对抗毛果芸香碱、组织胺及乙酰胆碱对离体肠肌的作用;本药不延长硫喷妥钠的作用时间.     

华山参对中枢神经系统的药理作用

作者研究了华山参(Physochlaina infundibularis Kuang)对中枢神经系统的药理作用.华山参煎剂腹腔注射对小白鼠的LD₅₀为43(28.7-64.5)克/公斤;腹腔注射1克/公斤使大白鼠防御运动性条件反射潜伏期延长,部分动物条件反射破坏及分化抑制有解除现象;灌胃给药(2克/公斤)仅使条件反射潜伏期延长.腹腔注射1-4克/公斤显著降低大、小白鼠和家兔的自由活动,维持3-6小时,但不降低小白鼠的被动活动.腹腔注射4克/公斤,能协同硫喷妥钠及水合氯醛对小白鼠的催眠、麻醉作用;降低苯丙胺、咖啡因对小白鼠的兴奋活动,但在10克/公斤时对本丙胺的毒性作用及士的宁,戊四唑性惊厥无影响.给狗灌胃2-5克/公斤,有明显的镇静作用,但不能对抗去水吗啡的催吐效果.     

清风藤硷甲的药理作用 Ⅰ.镇痛、消炎作用及急性毒性实验

一、清风藤硷甲50及100毫克/公斤给小白鼠腹腔注射能显著提高动物对热刺激的痛阈,其作用强度与吗啡比较约为1:2.5.二、清风藤硷甲60毫克/公斤腹腔注射对大白鼠甲醛性及蛋清性“关节炎”,无论预先给药或与产生”关节炎”同时给药,不但可使关节肿胀程度较对照组显著为少,且消退亦速.三、清风藤硷甲腹腔注射对小白鼠之半数致死量为285±29毫克/公斤.     

青藤碱的药理作用Ⅳ.青藤碱降压机制的研究

给麻醉狗、大白鼠和兔静脉注射青藤碱盐酸盐后,皆可产生肯定的降压作用.(?)只狗注射青藤碱(1毫克/公斤)后,平均降压面积为-40±3%.应用同量的药物反复注射三种动物都能出现快速耐受现象;以狗最为明显.在位狗心实验中发现青藤碱在降压同时并不抑制心脏,抗组织胺药不能影响其降压效果,对于M-胆碱反应系统并无影响.本药具抗肾上腺素作用和神经节阻断作用,且能抑制多种中枢性加压反射,故其降压机制可能系抗肾上腺素、阻断神经节和中枢作用的结果.     

黄耆的利尿与降压作用

给大白鼠皮下注射及麻醉狗静脉注射黄耆0.5克/公斤后,均可产生显著的利尿作用;给正常人口服0.2克/公斤后亦可产生显著的利尿作用.黄耆的利尿作用持续时间较长,给大白鼠皮下注射后,利尿作用可持续7天,连续给药7天后无耐受性.大白鼠皮下注射0.5克/公斤的利尿效价与氨茶碱0.05克/公斤及双氢氯噻嗪0.2毫克/公斤者相当.给麻醉狗静脉注射或灌胃黄耆0.5克/公斤后,均可引起明显的降压作用,重复静脉注射时出现快速耐受性.黄耆的毒性很小,给小白鼠灌胃75克/公斤无异常症状,小白鼠的半数致死量(腹腔注射)为40±5克/公斤,大白鼠慢性毒性试验未出现不良反应.     

抗肿瘤药物的研究 ⅩⅩ.樟州水仙总碱的疗效及其毒性

本文介绍的AC-445系自樟州水仙分离的总生物碱,具有一定的抗癌作用。以20-30毫克/公斤腹腔注射对大白鼠Jensen肉瘤,小白鼠Crocker肉瘤及Ehrlich腹水癌均有明显的疗效.小白鼠腹腔注射的念性LD₅₀为182毫克/公斤,小白鼠及大白鼠的亚急性LD₅₀分别为59及23毫克/公斤.在狗的急性毒性实验中,本药在注射初期能产生呕吐,但动物很快即可耐受.本药在1,4和16毫克/公斤时可使狗周围血中的白血球总数增加,且可维持较长时间.     

土青木香降压成分——广玉兰碱的药理作用

自土青木香中提出的广玉兰碱具有如下的药理作用:(1)麻醉猫静脉注射2毫克/公斤,降压达50—60%,持续90—120分钟;口服20—40毫克/公斤,也可得到与静脉注射相近的降压效果,不过作用发生较慢,而持续较久。(2)不麻醉动物:大白鼠腹腔注射20—40毫克/公斤,平均降压30%,持续达90分钟左右;口服100毫克/公斤,降压平均24%,持续时间120分钟;口服200毫克/公斤降压34.6%,持续135分钟,对肾性高血压犬,6毫克/公斤静脉注射,也有明显的降压作用,对舒张压的作用尤为明显。(3)广玉兰碱不具M-胆碱样作用,对N-胆碱反应系统尤以神经节有显著的阻断作用,但较C₆为弱;有微弱的箭毒样作用;对肾上腺素反应系统没有阻断作用,所以广玉兰碱的降压作用与神经节阻断作用有密切关系。此外,对颈总动脉阻断,电刺激坐骨神经向中端的加压反应均有抑制现象。(4)小白鼠一次静脉注射的LD₅₀为0.02克/公斤;长期口服其10倍剂量,并无明显的慢性毒性。根据家兔背部皮内试验,广玉兰碱用至10%的浓度,并无刺激现象。     

鱼腥草水溶性成分的药理研究

鱼腥草(Houttuynia cordata Thunb.)成分,据药典记载,其叶含槲皮甙,花穗含有异槲皮甙。本文将鱼腥草的水溶性成分(简称HC)和槲皮甙进行比较研究。对动物自发活动量研究表明,皮下注射20毫克/公斤槲皮甙与对照组无显著差异,而皮下注射200毫克/公斤HC则可抑制动物自发活动量38％。HC和槲皮甙分别延长己巴比妥钠(100毫克/公斤,腹腔注射)睡眠时间50～60分钟和30～40分钟。腹腔注射200毫克/公斤HC能完全抑制土的宁所致惊厥,但腹腔注射20毫克/公斤槲皮甙仅延长士的宁(1     

猪毛菜(茨蓬)浸膏对实验动物的药理研究

猪毛菜浸膏对麻醉动物有明显持久降压作用,无明显快速耐受現象。猪毛菜对乙酰胆碱及刺激迷走神經离中端所致降压作用无影响,阿託品不阻断猪毛菜的降压作用。双側迷走神經切断后,猪毛菜降压作用略減弱。猪毛菜不阻断頸上交感神經传导,亦无明显抗腎上腺素作用。猪毛菜抑制因压迫頸总动脉及刺激坐骨神經向中端所致的升压反射,二側竇神經切除亦不影响其降压作用。在猪毛菜引起降压作用时,带神經离体兔耳血管反射性扩张,因此推测猪毛菜对血管运动中枢或交感中枢有抑制作用。猪毛菜5,10克/公斤皮下注射能显著减少小白鼠自由活动。20克/公斤延长戊巴比妥鈉(35毫克/公斤)催眠作用的时間,并使非催眠剂量的水合氯醛(200毫克/公斤)产生催眠作用。但不能对抗中枢惊厥药(戊四氮及士的宁)的惊厥及致死作用。在小白鼠防御运动条件反射实驗中,皮下注射猪毛菜3克/公斤,对条件反射活动无明显影响。5克/公斤,10克/公斤时能使条件反射时延长,強化次数增加,分化相无变化。20克/公斤时条件反射显著抑制。5,10克/公斤皮下注射均能加速阳性条件反射消褪过程。小白鼠皮下注射猪毛菜LD₅₀为56克/公斤,大白鼠腹腔注射8克/公斤卽死亡。家兔口服(灌胃)40克/公斤未見毒性反应,80克/公斤时可見死亡。     

N-双(2-氯乙基)-N′-N″-二乙撑基磷酰胺对动物肿瘤的疗效及毒性

本文研究了17种磷酰胺氮芥类化合物,发現N-双(2-氯乙基)-N'-N"-二乙撐基磷酰胺(以下均簡称AT-222)具有較强的抗癌作用。主要結果如下:(1)腹腔注射AT-2221—2.5毫克/公斤对小白鼠肉瘤180,网織細胞肉瘤,AK肉瘤,梭形細胞肉瘤,大白鼠Jensen肉瘤和Walker癌肉瘤都有明显的抑制作用,口服給药时对Jensen肉瘤也有一定的疗效。但对Ehrlish癌固体型和腹水型則无明显的影响。(2)AT-222对小白鼠的急性和亚急性LD_(50)分別为19和4.7毫克/公斤,大白鼠的亚急性LD_(50)为2.7毫克/公斤(停药后观察3天)和1.9毫克/公斤(停药后观察10天)。(3)給狗靜脉注射AT-222 0.1毫克/公斤,其血象、大小便和体重均无明显改变。在0.3毫克/公斤組,給药第5天时白血球稍有下降,停药后逐渐恢复,解剖发現腸粘膜有出血点,脾淋巴細胞核和卵巢顆粒細胞核有固縮現象。0.9毫克/公斤組,于給药后第5天时白血球卽明显下降,停药后2—4天动物相继死亡,解剖检查发现各脏器均有弥蔓性出血,腸、胃腺体、腎上腺和睾丸均有明显萎縮。     

青藤碱的药理作用——Ⅴ.对防御性条件反射活动的影响

青藤碱具有多种中枢作用,研究青藤碱对条件反射活动的影响,对进一步分析青藤碱的中枢作用机制是有意义的.因此本文就青藤碱对小白鼠和猫的防御性条件反射的影响进行观察.(一)对小白鼠防御运动性条件反射的影响仿胥彬防御运动性条件反射木箱,以强风鸣声作阳性条件刺激,弱风鸣声作分化条件刺激.从给予强风鸣声至跑到木箱对侧的间隔时间,称为条件反射潜伏期.给药后给阳性条件刺激10秒钟动物不跑到木箱对侧称为条件反射消失,从弱风鸣声响后10秒内跑到木箱对侧称为分化抑制解除;当条件反射消失后接着给直流电作非条件刺激,刺激持续时间不超过10秒,如动物不跑到木箱对侧称为非条件反射消失.当条件反射形成后再进行分化,阳性和分化抑制性条件反射巩固和反射潜伏期基本稳定后进行实验.     

影响三价葡萄糖酸锑铵毒性的因素

动物实验已经证明三价葡萄糖酸锑铵(以后简称锑铵)的毒性约为酒石酸锑钾(以后简称吐酒石)的三分之一。用等毒性的剂量治疗动物感染血吸虫病时,锑铵的疗效优于吐酒石。临床实验的报告指出,锑铵的毒性反应较吐酒石轻,而疗效则最少和吐酒石相等。可见锑铵是治疗血吸虫病很有前途的药物。一般认为很多因素能影响含锑化合物的毒性。本文报告一些可能影响锑铵毒性的因素研究。     

The effect of benzodiazepines and atropine on exploratory behaviour and motor activity of mice

1. Male albino mice were watched in red light on a tunnel board to test exploration and their motor activity was assessed in an open cage, 30 min after intraperitoneal injection of drugs.

2. Atropine and methylatropine 5 or 10 mg/kg did not alter the motor activity of the mice, while chlordiazepoxide 25 or 50 mg/kg and diazepam 10 or 20 mg/kg increased the activity, especially at the lower of the two doses used.

3. All the compounds used except methylatropine adversely affected the exploratory behaviour.

4. When atropine 10 mg/kg was given with the benzodiazepines, the activity of the mice was reduced and exploratory behaviour was further impaired. Methylatropine did not have this effect.

     

Delta-9-tetrahydrocannabinol differentially suppresses emesis versus enhanced locomotor activity produced by chemically diverse dopamine D2/D3 receptor agonists in the least shrew (Cryptotis parva)

The principal psychoactive component of marijuana, delta-9-tetrahydrocannabinol (Delta9-THC), suppresses nausea and vomiting in cancer patients caused by chemotherapeutics such as cisplatin. Cisplatin induces vomiting via a number of emetic stimuli, including dopamine. Currently, there is controversy as to whether Delta9-THC can prevent emesis produced by dopaminergic agonists such as apomorphine. The present investigation utilizes the least shrew to evaluate the antiemetic potential and the cannabinoid receptor by which Delta9-THC may prevent emesis produced by four dopamine receptor agonists with differing selectivity for D2 and D3 receptors, i.e., a nonselective dopamine receptor agonist (apomorphine), a D2-preferring receptor agonist (quinpirole), and two D3-preferring receptor agonists (quinelorane and 7-OH DPAT). In addition, relative to its antiemetic doses, the motor suppressive doses of Delta9-THC in dopamine D2/D3-receptor-agonist-treated shrews were also evaluated. Thus, different groups of shrews were injected with either vehicle (V) or varying doses of Delta9-THC [0.5, 1, 2.5, 5, or 10 mg/kg, intraperitoneal (i.p.)] 10 min prior to administration of a 2 mg/kg dose of one of the four cited D2/D3 agonists. Immediately after the last injection, the frequency of vomiting for each shrew was recorded for the next 30 min. To investigate which cannabinoid receptor is involved in the antiemetic action of Delta9-THC, various doses of the CB1 receptor antagonist SR 141716A [0, 5, 10, and 20 mg/kg, subcutaneous (s.c.)] were administered to shrews 10 min prior to an injection of a fully effective antiemetic dose of Delta9-THC (5 mg/kg, i.p.). Ten minutes later, each treated shrew was administered with a 2 mg/kg dose of apomorphine. The emesis frequency was recorded for the next 30 min. For locomotor studies, different groups of shrews received either vehicle or various doses of Delta9-THC (0, 5, 10, 20, or 30 mg/kg) 10 min prior to an injection of vehicle or a 2 mg/kg dose of one of the four D2/D3 receptor agonists. The triad of motor behaviors (spontaneous locomotor activity, total duration of movement, and rearing frequency) were recorded for the next 30 min by a computerized video tracking system. Delta9-THC dose-dependently attenuated the frequency of emesis as well as fully protecting shrews from vomiting produced by each one of the four cited dopamine D2/D3 receptor agonists with ID50s ranging from 1 to 4 mg/kg. SR 141716A reversed the antiemetic activity of Delta9-THC against apomorphine-induced emesis. Delta9-THC also differentially suppressed the triad of motor activities in dopamine D2/D3-receptor-agonist-treated shrews with ID50s ranging from 7 to 21 mg/kg. The results suggest that Delta9-THC prevents emesis via cannabinoid CB1 receptors in a potent and dose-dependent manner in D2/D3-receptor-agonist-treated shrews at doses well below those which cause significant motor depression.     

Ascorbic acid antagonizes nicotine-induced place preference and behavioral sensitization in mice

In the present study, the influence of ascorbic acid on the nicotine-induced behavioral sensitization and conditioned place preference was investigated in mice. In the place preference paradigm, intraperitoneal (i.p.) nicotine (1 and 1.5 mg/kg, three drug sessions) but not ascorbic acid (1, 10, 100 and 1000 mg/kg) administration induced place preference. Ascorbic acid administration (10, 100 and 1000 mg/kg, i.p.) reduced both the acquisition and expression of nicotine-induced place conditioning. Locomotor sensitization in mice was produced by intraperitoneal injection of nicotine (0.25 mg/kg) for 7 consecutive days. On the 9th day of the experiments, activity of the mice was recorded after challenge with nicotine (0.1 mg/kg, i.p.). Ascorbic acid (10, 100 and 1000 mg/kg, i.p.) was injected 20 min before each injection of nicotine (acquisition of sensitization) or acutely 20 min before a challenge nicotine injection (expression of sensitization). It was shown that ascorbic acid attenuated the acquisition of nicotine sensitization in a dose-independent manner but the expression of nicotine-induced sensitization was not affected by ascorbic acid. In conclusion, it seems that ascorbic acid may interfere with nicotine-induced place preference and behavioral sensitization in mice.     

两面针结晶8的解痉和镇痛作用研究

结晶-8,是从两面针提出的一种单体。当浓度为1×10^-6～1×10^-4g/ml对正常离体豚鼠回肠活动无影响,但对乙酰胆硷、匹鲁卡品、氯化钡及组织胺所致肠肌收缩有明显的松弛作用;结晶-8腹腔注射10 mg/kg有明显抑制小鼠扭体反应;8～20 mg/kg明显提高家兔及大鼠痛阈,200μg/kg脑室注射亦有明显提高大鼠痛阈。其镇痛作用不被丙烯吗啡(5 mg/kg)所拮抗,而被利血平(4 mg/kg)所对抗。表明结晶-8的解痉作用直接作用于肠平滑肌。而镇痛作用具有中枢性,与吗啡受体无直接关系,但与脑内单胺类介质有关。     

刺乌头碱氢溴酸盐的药理作用研究

用热板,扭体反应(小鼠)和光热甩尾法测试表明,刺乌头碱均有镇痛作用。小鼠多次注射刺乌头碱后,再给予烯丙吗啡,不出现跳跃反应。对依赖吗啡大鼠或猴停药后的戒断症状无替代取消作用。猴长期注射刺乌头碱后停药不出现戒断综合症,表明刺乌头碱是一种不成瘾的止痛剂。刺乌头碱有较强的局部麻醉作用。对三联疫苗发热小鼠有解热作用。对大鼠甲醛性“关节炎”有消炎作用。     

Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB(1) receptor antagonist/inverse agonist SR 141716A.

There is substantial clinical evidence that Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and its synthetic analogs (nabilone and levonantradol) can prevent emesis in cancer patients receiving chemotherapy. Limited available animal studies also support the antiemetic potential of these cannabinoids. The present study investigates the mechanism of antiemetic action of cannabinoids in an established animal model of emesis, the least shew (Cryptotis parva). Since cannabinoid agonists prevent emesis, it was hypothesized that blockade of either the cannabinoid CB(1) receptor or the cannabinoid CB(2) receptor would induce vomiting. Thus, the emetic potential of SR 141716A (CB(1) receptor antagonist) or SR 144528 (CB(2) receptor antagonist) was investigated. Both intraperitoneal (0, 1, 2.5, 5, 10 and 20 mg/kg, n = 7-15 per group) and subcutaneous (0, 10, 20 and 40 mg/kg, n = 6-9 per group) administration of SR 141716A caused emesis (ED(50) = 5.52 +/- 1.23 and 20.2 +/- 1.02 mg/kg, respectively) in the least shrew in a dose-dependent manner. Indeed, both the frequency of emesis and the percentage of animals vomiting increased with increasing doses of SR 141716A. Significant effects were seen at the 10- and 20-mg/kg doses for the IP route, while only the 40-mg/kg dose produced significant emesis via the SC route. The CB(2) antagonist failed to produce emesis via either route of administration. SR 141716A at an IP dose of 20 mg/kg was used to induce emesis for drug interaction studies. Thus, varying doses of three different classes of cannabinoid agonists [CP 55, 940 (0, 0.1, 0.5 and 1 mg/kg), WIN 55, 212-2 (0, 1, 5 and 10 mg/kg), and Delta(9)-THC (0, 5, 10 and 20 mg/kg)], were administered IP to different groups of shrews 10 min prior to SR 141716A injection. The frequency of emesis was recorded for 30 min following the administration of SR 141716A. The order of potency for redcing both the frequency of emesis and the percentage of shrews vomiting was CP 55, 940 > WIN 55, 212-2 > Delta(9)-THC which is consistent with an action on the CB(1) receptor. These results suggest that the antiemetic activity of Delta(9)-THC and its synthetic analogs reside in their ability to stimulate the cannabinoid CB(1) receptor. Furthermore, the antiemetic potency of CP 55, 940 is 45 times greater than Delta(9)-THC. On the other hand, blockade of CB(1) receptors can induce vomiting, which implicates an important role for endogenous cannabinoids in emetic circuits.