伪石蒜硷的抗瘤及药理研究

伪石蒜硷是从石蒜科植物水仙及石蒜中提得的生物硷。其游离硷及盐酸盐在动物耐受剂量下,对大鼠W-256的生长有明显的抑制作用,抑制率在49～76％之间,统计学上差异非常显著。对小鼠肝癌、艾氏腹水癌皮下型、S-180的抑制作用不明显。已测得伪石蒜硷对大鼠一次腹腔注射的LD_(50)为110(92.4～131)mg/kg。对猫静脉滴注可致缓慢血压下降,滴注致死要求很大剂量(平均881mg/kg)。根据推算现在的病人试用剂量(～1mg/kg/日)是安全的。狗的亚急性毒性试验表明,此药可引起恶心、呕吐、厌食,但对骨髓无明显抑制作用。用药后曾见血中非蛋白氮值上升,考虑为肾前因素引起。病理解剖心、肝、脾、肺、肾、肠各脏器均未见明显病变。药物正开始进行Ⅰ期临床试用中。     

抗癌新药-乙双吗啉(AT-1727)的药理研究

乙双吗啉(AT-1727)是我国合成的一种抗癌新药。它是一种双内酰亚胺化合物,实验证明,乙双吗啉对小鼠肉瘤S₃₇、S₁₈₀有显著抗肿瘤作用,对ECS,HCS,脑瘤B₂₂及L₆₁₅等移植性肿瘤亦有明显抗肿瘤作用。它对S₃₇的50%抑制剂量(ID₅₀)为1.88 mg/kg(ip)及6.61 mg/kg(po)。其抗肿瘤作用与给药方案有一定关系。乙双吗啉对小白鼠毒性LD₅₀为372.8±27.mg/kg(ip)及243.8±26.1 mg/kg(po)。因此,乙双吗啉腹腔注射及口服时,对S₃₇的化疗指数分别为47.5及36.9。给健康犬肌肉注射乙双吗啉25及50 mg/kg/天,连用10天,除出现食量减少,白细胞轻度下降外,对红细胞,血小板、肝、肾功能均无明显影响。乙双吗啉对以溶血素反应为指标的体液免疫有抑制作用;对以移植物抗宿主反应为指标的细胞免疫则无抑制作用。     

烟浪丁的抗心律失常作用

NICO 100 mg/kg iv,可明显对抗乌头碱和BaCl₂诱发大鼠及氯仿-肾上腺素引起兔的心律失常;降低CaCl₂所致的大鼠室颤率;提高豚鼠心脏哇巴因中毒时的耐量。50 mg/kg iv,也可预防结扎大鼠左冠状动脉引起的心律失常。50～100 mg/kg ip,能降低氯仿或ACh—CaCl₂引起的小鼠室颤率或房颤(扑)率。NICO可减慢豚鼠心率,且可拮抗异丙肾上腺素的正性变率作用。     

抗疟新药咯萘啶对大鼠胚胎毒性的观察

抗疟新药咯萘啶以1100 mg/kg/d×1,330 mg/kg/d×3,165 mg/kg/d×3和84 mg/kg/d×3四个剂量组分别于母鼠妊娠第7天(D₇)开始每日灌胃一次。另设空白对照组及阳性对照组(敌枯双5 mg/kg/d×7)。妊娠D₂₀杀鼠检查胚胎。结果表明:咯萘啶各组均引起胚胎早期吸收率升高,并随剂量递增而增加。该药还能延迟大鼠胚胎胸骨与枕骨的骨化。各试验组中未见胎鼠外形、内脏及其它骨骼畸形。可见咯萘啶对大鼠有较明显的胚胎毒性。     

肾上腺素能神经阻滞剂二甲基哌啶乙胍的药理

麻醉猫静注二甲基哌啶乙胍(BD-38)1～5mg/kg或十二指肠内注入10mg/kg,麻醉狗静注5mg/kg,均引起血压显著下降,心电图无明显的改变。BD-38部分抑制电刺激离体豚鼠回肠壁的收缩;显著地阻断电刺激动脉周围神经引起的回肠抑制性(松弛)反应。BD-38可明显地抑制电刺激猫内脏神经离中端所引起的升压。清醒猫静脉注射胍乙啶和BD-38(5或10mg/kg)引起瞬膜松弛的作用强度相同。清醒猫灌胃给胍乙啶和BD-38(10mg/kg),胍乙啶的瞬膜松弛作用强度只有BD-38的一半,增加剂量至20mg/kg,才达到BD-38组的松弛程度,说明BD-38胃肠道吸收较胍乙啶为优。电刺激猫迷走神经外周端引起的降压和心率变慢,给BD-38后稍有阻断,1/2小时内恢复。对乙酰胆硷的作用无明显改变。BD-38也能抑制因阻断颈总动脉引起的加压反射。离体豚鼠心肺标本,血中BD-38浓度为0.25mg/ml,对心率、心输出量无改变,浓度增至2mg/ml,也不抑制心脏。BD-38不影响洋地黄毒甙的毒性。狗亚急性毒性试验,未发现对生长和肝功能的影响。BD-38具有持久的降压效果、胃肠道吸收良好、静注无急性拟交感反应、对心脏无直接抑制作用,值得临床试用。     

肾上腺素能神经阻滞剂二甲基哌啶乙胍的药理

麻醉猫静注二甲基哌啶乙胍(BD-38)1～5mg/kg或十二指肠内注入10mg/kg,麻醉狗静注5mg/kg,均引起血压显著下降,心电图无明显的改变。 BD-38部分抑制电刺激离体豚鼠回肠壁的收缩;显著地阻断电刺激动脉周围神经引起的回肠抑制性(松弛)反应。BD-38可明显地抑制电刺激猫内脏神经离中端所引起的升压。清醒猫静脉注射胍乙啶和BD-38(5或10mg/kg)引起瞬膜松弛的作用强度相同。清醒猫灌胃给胍乙啶和BD-38(10mg/kg),胍乙啶的瞬膜松弛作用强度只有BD-38的一半,增加剂量至20mg/kg,才达到BD-38组的松弛程度,说明BD-38胃肠道吸收较胍乙啶为优。 电刺激猫迷走神经外周端引起的降压和心率变慢,给BD-38后稍有阻断,1/2小时内恢复。对乙酰胆硷的作用无明显改变。BD-38也能抑制因阻断颈总动脉引起的加压反射。 离体豚鼠心肺标本,血中BD-38浓度为0.25mg/ml,对心率、心输出量无改变,浓度增至2mg/ml,也不抑制心脏。BD-38不影响洋地黄毒甙的毒性。 狗亚急性毒性试验,未发现对生长和肝功能的影响。BD-38具有持久的降压效果、胃肠道吸收良好、静注无急性拟交感反应、对心脏无直接抑制作用,值得临床试用。     

к-硒化卡拉胶对免疫抑制小鼠淋巴细胞增殖及抗体形成细胞的影响(英文)

硒化卡拉胶是一个新的含硒有机化合物。本文主要观察它对环磷酰胺引致免疫抑制小鼠的淋巴细胞增殖及抗体形成细胞(PFC)的影响。研究结果表明,环磷酰胺可明显抑制小鼠淋巴细胞增殖及抗体形成细胞数。硒化卡拉胶2或12 mg/kg po qd×20～40可明显刺激免疫抑制小鼠的淋巴细胞增殖或抗体形成细胞,但大剂量硒化卡拉胶(72 mg/kg)不能显示稳定的刺激作用,在某些条件下反而转向抑制作用。     

к-硒化卡拉胶对免疫抑制小鼠淋巴细胞增殖及抗体形成细胞的影响(英文)

硒化卡拉胶是一个新的含硒有机化合物。本文主要观察它对环磷酰胺引致免疫抑制小鼠的淋巴细胞增殖及抗体形成细胞(PFC)的影响。研究结果表明,环磷酰胺可明显抑制小鼠淋巴细胞增殖及抗体形成细胞数。硒化卡拉胶2或12 mg/kg po qd×20～40可明显刺激免疫抑制小鼠的淋巴细胞增殖或抗体形成细胞,但大剂量硒化卡拉胶(72 mg/kg)不能显示稳定的刺激作用,在某些条件下反而转向抑制作用。     

复方前列宝抑制前列腺增生及抗炎作用的研究

复方前列宝口服或腹腔注射给药均能明显抑制由丙酸睾丸酮(50mg/kg)引起的小鼠前列腺增生。其口服剂量200mg/kg、腹腔注射剂量400mg/kg时与阳性药物安尿通的口服剂量800mg/kg、腹腔注射剂量1200mg/kg的药效相近。小鼠口服复方前列宝后,对角叉莱胶引起的足趾肿胀有明显的抑制作用,其剂量为400mg/kg时的抑制作用较氢化可的松25mg/kg时强。     

石蒜碱内铵醋酸盐对正常和带瘤小鼠免疫功能的影响

本文研究了抗癌新药石蒜碱内铵醋酸盐(AT-1840,Lyc)对正常和带瘤小鼠免疫功能的影响。Lyc 10mg/kg ip 5～6d可明显抑制ICR小鼠对羊红细胞(SRBC)引起的迟发型超敏反应(DTH),显著降低C57/BL小鼠的胸腺重量。对脾脏的淋巴细胞转化和空斑形成细胞(PFC)及血清中溶血素和IgG没有明显作用,但可显著升高SRBC致敏的正常和带瘤小鼠中血清补体C3的含量。Lyc还能扭转带瘤小鼠脾脏PFC的明显下降,而对淋巴细胞转化及血清IgG却呈抑制作用。实验结果表明Lyc对细胞免疫有一定的抑制作用;但可以调节带瘤小鼠部分体液免疫功能的缺陷。     

抗肿瘤药物的研究 Ⅺ.对-双(β-氯乙基)氨甲基苯丙氨酸(AT-290)的毒性及疗效

本文介绍新的氮芥衍生物AT-290 卽对-双(β-氯乙基)氨甲基苯丙氨酸二盐酸盐的毒性试验及实验治疗的结果。1.本药在小鼠腹腔注射的急性LD₅₀为4毫克/公斤,亚急性口服和腹腔注射的LD₅₀分别为11及1.6毫克/公斤,大鼠腹腔注射的亚急性LD₅₀为1毫克/公斤。2.狗毒性试验证明,AT-290 在75微克/公斤静脉注射每天1次连续10天,对狗的一般状态、体重、红、白血球数、血小板数、出血时间、凝血时间、尿及心电图检查均无明显影响;但却对淋巴细胞表现出明显抑制作用。150及300微克/公斤时,可抑制动物的骨髓机能,主要表现为白血球总数及血小板减少、出血时间延长、骨髓中幼稚细胞消失,对淋巴球的作用与75微克/公斤组同。这些情况在150微克/公斤组停药后一定时间自行恢复,而大剂量组(300微克/公斤)则动物死亡。3.本药腹腔注射时对三种小白鼠腹水型肿瘤(Ehrlich腹水癌、梭形细胞肉瘤腹水型及腹水型乳腺癌)均有明显抑制作用,可延长动物的生存时间至2倍以上,对小白鼠实体型肿瘤(淋巴白血病L-2、Ehrlich癌、Crocker肉瘤及梭形细胞肉瘤) 均无明显抑制作用。对大白鼠Jensen肉瘤及纤维肉瘤M-57疗效则很显著。     

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.     

中国萝芙木的药理研究,Ⅱ.海南岛萝芙木的降压作用和毒性试验

在发现广东大陆部分出产蘿芙木后,植物学家又相继在海南岛、云南和广西发现了蘿芙木,经鉴定和广东所产为同一品种,即Rauwolfia verticillata (Lour.) Baill. 我们在肯定了广东所产蘿芙木叶的粗制剂和生物硷的降压作用后,首先用海南岛所产叶的粗制剂物和生物硷进行实验,结果也发现它们有显著的降压作用。由于化学研究指出根含生物硷较多,因而又进行试验,肯定了根的生物硷的降压作用。此外,又进行     

Disposition of a new tetrahydrocarbazole analgesic drug in laboratory animals and man

1. The disposition of AY-30,068 (I), a new tetrahydrocarbazole analgesic drug, was studied in mice, rats, dogs, rhesus monkeys, and man.

2. Oral doses of the ¹⁴C-labelled drug in aqueous solution were well absorbed in rodents, but absorption of oral doses of the crystalline drug in dogs was poor. Due to the virtual absence of serum metabolites in rats and dogs, the bioavailability of I was nearly identical to the extent of absorption. Although a small first-pass effect was observed in mice, unchanged I represented a major portion of serum radioactivity.

3. A linear increase in the serum concentrations of I occurred at doses between 0.05 and 25?mg/kg in rats, 0.1 and 50?mg/kg in dogs, and 1–160?mg in man. In rhesus monkeys given a 0.5?mg/kg oral dose, the C_max and AUC of I were similar to values obtained following a corresponding dose in dogs.

4. After i.v. administration of a 1.0?mg/kg dose the terminal elimination half-life (t1/2β) of I was 4?h in mice and 9–10h in rats and dogs. In rodents, dogs, and several human subjects, the elimination of I was interrupted by secondary peaks. Enterohepatic circulation was confirmed in bile duct cannulated rats, where the t1/2β of I was decreased to 2.4?h. In rodents the serum clearance and apparent volume of distribution of I were 0.04–0.21/kg.?h and 0.5–0.81/kg, respectively, and 0.61/kg.h and 9.81/kg in dogs.

5. In rodents and dogs dosed with ¹⁴C-labelled I, radioactivity was excreted almost entirely in the faeces. No unchanged I was detected in rat bile, while about 70% of the radioactivity corresponded to conjugates of parent drug.     

中国萝芙木的药理研究,Ⅰ.广东产萝芙木叶子及其生物硷的降压作用

中国蘿芙木经中国科学院华南植物研究所鉴定为Rauwolfia verticicillata (Lour.) Baill.赵承嘏首先报告从根中提取出“蘿芙甲素”,并说明有降压作用。在本文初报发表的同时,林吉强等也发表了“蘿芙甲素”降压作用的初报。接着罗潜等又发表了根皮有降压作用的初报。我们在肯定广东所产蘿芙木的根和叶的粗制剂能使麻醉动物的血压下降以后,还试用叶的粗制剂治疗了三只有高血压症的狗,结果表现该制剂有显著的降压作用。随后又将从叶提出的生物硷给高血压鼠口服,也有明显的降压作用。     

Safety evaluation studies on oxisuran,a differential inhibitor of cell-mediated hypersensitivity

Preclinical toxicity studies were conducted on oxisuran, 2-[(methylsulfinyl) acetyl]-pyridine, an immunosuppressant with selective inhibition of cell-mediated hypersensitivity. Oral LD50 values were 5280 and 6610 mg/kg in female mice and rabbits, respectively, and 6550 mg/kg in female and male rats. An LD50 could not be established in dogs because of emesis at a dose of 5000 mg/kg. Intravenous LD50 values were 2510 mg/kg for mice and 1800 mg/kg for female and male rats. Feeding the drug in the diet to rats at dosages of 20, 100, 300, and 1000 mg/kg for 13 weeks caused a slight reduction in food consumption and body weight gain at the higher dosages. At doses of 100, 300, and 1000 mg/kg, cloudy swelling and fatty infiltration of the liver and hyperplasia of the thyroid occurred in dose-related patterns (mild to moderate) in many animals. No significant changes were found in thyroid function studies which included thyroid uptake (¹²⁵I) and T₃ and T₄ determinations. The thyroid hyperplasia seen at 13 weeks disappeared within a few days of drug withdrawal. Oral daily administration of 20, 125, 500, and 2000 mg/kg of oxisuran to dogs for 13 weeks produced a decrease in food consumption and body weight in the latter phase of the study in the males treated with the high dose. Serum glutamic-pyruvic transaminase was mildly elevated in dogs given 2000 mg/kg. At this dose, some animals showed slightly increased thyroid and liver weights. Histologically, thyroid hyperplasia was moderate in females (2000 mg/kg) and mild to moderate in males (125, 500, and 2000 mg/kg). The liver, in the animals of the high-dose group showed a slight degree of vacuolar changes and bile retention. Thyroidal radioiodine uptake (¹²⁵I), PBI, TI, and serum cholesterol were slightly below normal values. The histology and function tests of the thyroid were within normal ranges at 4 weeks post-treatment.     

Analgesic activity of Gleditsia triacanthos methanolic fruit extract and its saponin-containing fraction

Context: Gleditsia triacanthos L. (Leguminosae) pods are used in folk medicine for pain relief as anodyne and narcotic.

Objective: The objective of this study is to evaluate analgesic activity of Gleditsia triacanthos methanolic fruit extract (MEGT) and its saponin-containing fraction (SFGT).

Materials and methods: Peripheral analgesic activity was assessed using the acetic acid-induced writhing model in mice at doses of 140, 280, and 560?mg/kg and formalin test in rats at 100, 200, and 400?mg/kg doses. Central analgesic activity was evaluated using the hotplate method in rats (100, 200, and 400?mg/kg).

Results: In the writhing test, six mice groups treated with MEGT and SFGT found ED₅₀ values 268.2 and 161.2?mg/kg, respectively, displayed a significant decrease in writhing count compared with the group treated with standard drug indomethacin (14?mg/kg). SFGT (280 and 560?mg/kg) showed 64.94 and 70.78% protection, respectively, which are more than double % protection caused by indomethacin (31.82%). In the formalin test, MEGT and SFGT (ED₅₀ values 287.6 and 283.4?mg/kg for phase I as well as 295.1 and 290.4?mg/kg for phase II, respectively) at 400?mg/kg showed significant % inhibition in both phase I (18.86 and 52.57%) and phase II (39.36 and 44.29%) with reference to 10?mg/kg indomethacin (56.0 and 32.29%). MEGT and SFGT caused significant delay in responses in hotplate model (ED₅₀ values 155.4 and 200.6?mg/kg, respectively) compared with that of 10?mg/kg indomethacin at 30, 60, and 120?min.

Discussion and conclusion: Central and peripheral analgesic activities induced by Gleditsia triacanthos fruits might account for its uses in folk medicine.     

治疗血吸虫病药:对氨苯氧庚烷的毒性及药理作用

1.对氮苯氧庚烷对小鼠的半数致死量口服为1260毫克/公斤,静脉注射为195毫克/公斤。小白鼠每日口服50-200毫克/公斤,连续两周,因影响食欲致使体重的增加受到抑制,停药后即渐恢复。2.对氨苯氧庚烷对麻醉猫和狗的血压,在静脉注射时有显著而短暂的降低,剂最愈大或注射速度愈快,血压下降亦愈多。3.对于麻醉猫的迴肠及豚鼠离休迴肠,对氨苯氧庚烷均有明显抑制作用。对氨苯氧庚烷并能对抗组织胺、乙醯胆龄及氯化钡对离体豚鼠迴肠的作用。对在体家兔子宫有收缩作用,而对离体子宫则有抑制作用。     

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.     

新利胆药亮菌甲素的药理和毒性研究

亮菌甲素是从假蜜环菌(亮菌)中提取的、对胆道系统具有活性的成分之一。麻醉犬静脉注射本品后能松弛总胆管末端括约肌的紧张度,同时能使肝脏分泌胆汁量明显增加。麻醉大白鼠十二指肠给药或肌内注射本品后,均能促进肝脏分泌胆汁。麻醉犬静脉注射本品后还能引起十二指肠松弛、血压降低、心率减慢,作用均轻度而短暂。小白鼠腹腔注射和口服本品的急性LD₅₀分别为980mg/kg和>5000mg/kg。以人用每天最高剂量的25～125倍分别肌内注射于大白鼠和狗,每天一次,连续三个月,结果未见到明显的毒副作用。