甲基莲心碱的降压作用

甲基莲心碱对麻醉、清醒的正常大鼠,肾性、D0CA盐型高血压大鼠,麻醉猫、清醒正常家兔都能引起快速、剂量依赖性降压作用,猫椎动脉注射及脑室内注射甲基莲心碱0.6mg/kg无明显降压作用。表明甲基莲心碱是一种有效的抗高血压药,对血管平滑肌有直接扩张作用。     

三种国产藜芦碱(邢氏藜芦碱、毛叶藜芦碱、马氏藜芦碱)的降血压作用及其机制

1.麻醉猫靜脉注射馬氏藜芦碱(5—25微克/公斤)毛叶藜芦碱(25微克/公斤)邢氏藜芦碱(50微克/公斤)能使血压下降20—70%,历时5—80分钟,降压时伴有心率減慢,呼吸抑制或暫停。肌肉注射10倍于靜脉注射降压量,口服15倍于靜脉注射降压量有降压作用,可維持2—3小时,唯部分动物死于实驗中。无明显快速耐受現象。2.降压作用与腎上腺素、去甲腎上腺素无关,而与迷走神經、毒蕈碱-胆碱反应系統有关。3.降压过程中,頸动脉加压反射減弱,刺激迷走神經及坐骨神經向中端引起的血压效应被抑制。4.舌下动脉給药,或結扎頸內、外动脉从甲状腺上动脉給药,結果馬氏藜芦碱1微克/公斤,毛叶藜芦碱2微克/公斤,邢氏藜芦碱5微克/公斤,均可引起血压下降。5.三种国产藜芦碱于离体兔耳及猫后肢未見直接血管扩张作用。6.三种国产藜芦碱大量时(馬氏碱75—200微克/公斤,毛叶碱200微克/公斤,邢氏碱400微克/公斤)除引起明显的哑噁心、呕吐外,未見其他特殊症状。氯丙嗪預先应用可防止此反应。     

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。     

莲子心生物碱Nn-9的降压机制

蓮子心非結晶生物碱Nn-9对麻醉猫靜脉注射1-2毫克/公斤可降低原血压水平約50%,維持2-3小时。狗血压于1/2小时卽恢复,兔子不降压。有快速耐受性。經苯海拉明及异丙嗪处理猫再注射Nn-9碱2—3.5毫克/公斤,降压作用明显減弱。对靜脉注射組織胺引起的降压被Nn-9所減弱。猫靜脉注射2毫克/公斤的Nn-9后,血压下降伴随脑血管阻力減低,动脉注射0.2毫克/公斤使脑血流及后肢血流均增加,血管阻力減低。脊猫靜脉注射2毫克/公斤,有明显的降压出现。靜脉注射腎上腺素、去甲腎上腺素及脑垂体后叶素或在第七頸椎以下加高脊髓腔压所引起的升压反应均被抑制,历1/2—1小时恢复。电刺激頸交感神經节节前纤維所致的瞬膜收縮也受到抑制。对副交感神經节及M-胆碱反应系統无明显影响。頸动脉注射药液也出现降压,并抑制頸总动脉血流阻断所引起的升压反应。总結实驗結果,Nn-9的降压机制主要是释放組織胺,使外周血管扩张,其次神經因素也有关。     

甲基莲心碱对大鼠血压、血小板聚集和血栓形成的影响

采用比浊法研究甲基莲心碱对大鼠血压及血小板聚集、血栓形成的影响，结果显示甲基莲心碱在降低血压的同时，能剂量依赖性地抑制ＡＤＰ和胶原诱导的正常大鼠、肾性高血压大鼠和高脂喂养大鼠血小板聚集；甲基莲心碱亦能明显延长电刺激大鼠颈动脉闭塞性血栓形成时间。此结果表明甲基莲心碱具有降压与抗血小板聚集和血栓形成的双重作用。     

使用神经节阻滞剂行控制性低血压之经验

(一)本文报告使用阿佛那(Arfonad)及六甲銨(Hexamethonium)行控制性低血压麻醉共563例之临床經驗。 (二)綜合文献叙述了阿佛那及六甲銨之药理作用,并将著者应用此二种药物行控制性低血压之操作方法作了介紹。 (三)将临床应用阿佛那、六甲銨行控制性低血压之563例經驗按性别、年龄,施行手术之种类、低血压維持之水平、給药后脉搏之变化、低血压期間呼吸之情况、血压恢复之情况、神經节阻滞剂之用量以及并发症等方面作了分析。 (四)对阿佛那及六甲銨之给药方法,維持血压水平之原則、阿佛那及六甲銨之优缺点、以及根据其优缺点对适应症之选擇等方面,結合临床經验作了詳細討論。 (五)最后将利血平作为麻醉前用药及普鲁卡因銨輔助降压之效果,結合临床观察給以适当评价。但因經驗很少,尚有待于进一步之研究。     

甲基莲心碱治疗心血管疾病的药理作用及其机制研究进展

甲基莲心碱是从睡莲科植物莲Nelumbo nucifera成熟种子的胚芽中提取出的一种双苄基异喹啉类生物碱,具有抗动脉粥样硬化、抗高血压、抗血栓、抗糖尿病血管病变和血管保护作用、抗心律失常等作用。心血管疾病是全球发病率和死亡率最高的一类疾病,包括心绞痛、高血压、高血脂、动脉粥样硬化。近年来,有研究表明甲基莲心碱对心血管疾病防治具有疗效好、副作用低的特点。对甲基莲心碱在心血管疾病中的药理作用及其机制进行综述,为甲基莲心碱的药物研发和临床应用提供参考。     

甲基莲心碱的药理作用

甲基莲心碱是一种双苄基异喹啉类生物碱。该文就甲基莲心碱的扩血管、降压 ,抗心律失常 ,抗血小板聚集 ,抗血栓形成 ,抗氧化 ,抗有机磷农药中毒 ,抗瘢痕形成以及化疗增敏等药理作用作一综述     

甲基莲心碱对大鼠心电图和蟾蜍坐骨神经动作电位的影响

在麻醉大鼠观察了恒速iv甲基莲心碱对ECG的影响,并与奎尼丁和粉防己碱进行了对比性研究。甲基莲心碱对大鼠ECG的影响与奎尼丁相似,剂量(2～40mg/kg)依赖性地延长P-R和Q-T,使QRS增宽;粉防己碱不增宽QRS。结果显示甲基莲心碱作用机理与奎尼丁相似,不同于粉防己碱。甲基莲心碱与奎尼丁都可依浓度抑制蟾蜍坐骨神经APA,二者作用强度相近。     

19-去甲基甾体化合物

許多甾体化合物,如性激素、心脏有效素等具有重要生理作用,且已用于临床。近年来許多学者均致力于有效甾体物結构与疗效間关系的研究,希望得到具有很強生理作用而又有比較簡单分子結构的甾体物。其中部分的工作是19-去甲基甾体化合物結构改变的研究。在1944年Ehrenstein选择了毒毛旋花子配基Strophanthindin(Ⅰ)为原料以合成19-去甲基黃体酮,因为毒毛旋花子配基分子中19位碳上是一个醛基,易于設法除去。此物經药理試驗証明有比黃体酮更高的生理活力。虽然如此,19-去甲基甾体物仍然沒有     

Antiheparin activity of polymers based on the alkaloid, lupinine]

Antiheparin activity and acute toxicity of a monomer and polymer quaternary ammonium salts obtained on the basis of the alkaloid lupinine were investigated. The monomer was shown to have no antiheparin activity even when administered in high doses. Lupinine polymetakryloyl iodoethylate is a selective heparin antagonist. This activity of polymers is relative to the extent of polymerization. A compound with a molecular weight of 20 000 turned out the most effective in the tested series of ready-made polymers. Acute toxicity of polycations is considerably less than that elicited by the monomer. The effect of heparin complete neutralization is accompanied by transitory thrombocytopenia.     

Mechanism of intestinal transport of an organic cation, tributylmethylammonium in Caco-2 cell monolayers

Many quaternary ammonium salts are incompletely absorbed after their oral administration and may also be actively secreted into the intestine. However, the underlying mechanism(s) that control the transport of these cations across the intestinal epithelium is not well understood. In this study, the mechanism of absorption of quaternary ammonium salts was investigated using Caco-2 cell monolayers, a human colon carcinoma cell line. Tributylmethyl-ammonium (TBuMA) was used as a model quaternary ammonium salts. When TBuMA was administrated at a dose of 13.3 imole/kg via iv and oral routes, the AUC values were 783.7±43.6 and 249.1±28.0 μmole·min/L for iv and oral administration, indicating a lower oral bioavailability of TBuMA (35.6%). The apparent permeability across Caco-2 monolayers from the basal to the apical side was 1.3 times (p<0.05) greater than that from the apical to the basal side, indicating a net secretion of TBuMA in the intestine. This secretion appeared to be responsible for the low oral bioavailability of the compound, probably mediated by p-gp (p-glycoprotein) located in the apical membrane. In addition, the uptake of TBuMA by the apical membrane showed a Na⁺ dependency. Thus, TBuMA appears to absorbed via a Na⁺ dependent carrier and is then secreted via p-gp related carriers.     

益母草生物硷之研究(第一报) 关于Stachydrine的分离鉴定

用蓝氏铵盐沉淀法从益母草Leonurus sibiricus L.的叶子中分得的一种生物硷,其pH试验,干馏,元素分析及混熔试验之结果都证实与Stachydrine为同一物质,著者发现用氢氧化钾干镏时产生二甲胺,而用碱石灰干馏时则产生三甲胺。     

Synthesis of new antirusty disinfectants. I]

New quaternary ammonium salts [N-alkyl-N-2-hydroxyethyl-N,N-dimethylammonium ethyl phosphate (21, 22), isopropyl phosphate (23), n-butyl phosphate (24) and N-alkyl-N-2-hydroxy-3-phenoxypropyl-N,N-dimethylammonium ethyl phosphate (25, 26), isopropyl phosphate (27), n-butyl phosphate (28) and bis(N-alkyl-N-2-hydroxy-3-phenoxypropyl-N,N-dimethylammonium) malate (29), fumarate (30), succinate (31), adipate (32) and N-alkyl-N-2-hydroxy-3-phenoxypropyl-N,N-dimethylammonium tartrate (33)] were synthesized by alkylation of the corresponding trialkylammonium salts with various epoxy compounds. The new quaternary ammonium salts showed much greater bactericidal activities and antirusting effects than those of benzalkonium chloride. They had also good compatibilities since no precipitate was observed if the solution of any anionic surface active agents were added to the solution of these new quaternary ammonium salts. This property is the same as that of amphoteric surface active agents.     

Steroidal monoquaternary ammonium salts with non-depolarizing neuromuscular blocking activity

A series of ten 2β- or 3α-steroidal monoquaternary ammonium salts, having androstane or pregnane skeletons and related in structure to acetylcholine by possession of an oxygen function on the carbon atom next but one to the quaternary nitrogen atom, were investigated for neuromuscular blocking activity in vivo in the cat, hen and mouse and in vitro on the frog rectus muscle and on the rat phrenic nerve diaphragm preparation. All compounds displayed typical non-depolarizing activity, the duration of block being significantly less than that for (+)-tubocurarine in the cat and the hen. The potency of the salts was low with the most active compound, 3α-acetoxy-2β-piperidino-5α-androstan-17-one methobromide, being 1/16th as active on a molar basis in the cat as (+)-tubocurarine.     

毛叶轮环藤生物碱的肌松药理作用研究

本文研究了从毛叶轮环藤分离到的汉防己甲素,高阿洛莫林碱,左旋箭毒碱和异谷树碱的肌松作用。家免垂头试验表明,他们的碘甲烷盐均有肌松作用,但以左旋箭毒碱和高阿洛莫林碱的作用较强。将左旋箭毒碱制备成二甲基左旋箭毒碱氯甲烷盐衍生物后,肌松作用增强1.5～3倍。对小鼠,家免,猫和狗的肌松作用比右旋筒箭毒碱约强0.5～4倍,对大鼠的肌松作用强度与右旋筒箭毒碱相当。左旋箭毒碱,二甲基左旋箭毒碱及高阿洛莫林碱的作用均类似于右旋筒箭毒碱,属于非去极化型肌松剂。给麻醉猫、狗快速静注2～3倍肌松剂量的左旋箭毒碱或二甲基左旋箭毒碱,有降压和组胺释放作用。对猫颈交感神经节无抑制作用。对离体家兔及豚鼠廻肠的阿托品样作用很弱。家兔连续静注达40～50倍垂头剂量,对心电图无明显影响,静注5～10倍垂头剂量,48-72小时后剖杀检查,未见对内脏器官有明显病理损害。小鼠及大鼠试验结果表明二甲基左旋箭毒碱的治疗指数高于右旋筒箭毒碱。     

Ion exchange interactions on silica gel layers. II. Halogen salts of compounds containing organic tertiary and quaternary nitrogen

Primary and secondary ion exchanges--of hydrochloric acid and hydrobromic acid salts of well hydrolyzing organic bases as well as quaternary ammonium bromide which are important drug substance--taking place on silica gel using methanol as mobile phase have been investigated by thin-layer chromatographic and spectrophotometric methods. In case of tertiary ammonium salts (hydrolyzing salts) basis linked to silanate ion and halogen acid have been formed by primary ion exchange. During secondary ion exchange halogen acid has exchanged metal ions linked to silanate ions on the layer. In case of non hydrolyzing salts, the quaternary ammonium bromide salts it could not surely be proved by the applied methods whether primary ion exchange had been followed by secondary ion exchange or only primary ion exchange had occurred.     

恩其明(AT-1840)开环类似物的合成和抗癌作用 1.通过光化反应合成取代-2-羟基-菲啶溴烷季铵盐

根据恩其明(ungeremine,1.)分子中存在次甲基N-O-O三角和内铵盐结构,这可能和其抗肿瘤活性有密切关系的设想,合成了它的开环类似物2-羟基-8,9-次甲二氧基菲啶溴甲(或乙)烷季铵盐(3a和3b)和2-羟基-8,9-二甲氧基菲啶甲(或乙)烷季铵盐(4a和4b)等有关化合物,作为抗肿瘤作用的比较,以探讨恩其明的构效关系。动物试验表明:化合物3a对小鼠艾氏腹水癌有明显抑制作用,小鼠生命时间延长130～140%,其它化合物则无明显活性。     

Tertiary 3- and 4-haloalkylamine analogues of oxotremorine as prodrugs of potent muscarinic agonists

A series of tertiary 3- and 4-haloalkylamines related to the muscarinic agent oxotremorine was synthesized. The compounds cyclized in neutral aqueous solution to quaternary ammonium salts, which, in contrast to the parent haloalkylamines, were potent muscarinic agonists in vitro. When administered systemically to mice, the haloalkylamines produced central (tremor and analgesia) and peripheral (salivation) muscarinic effects. Central potency was dependent on the rate of cyclization and on the route of administration. The N-methyl-N-(4-chlorobutyl)amine derivative 7 cyclized rapidly (t1/2 less than 0.4 min at 37 degrees C) and elicited tremor on iv but not on ip injection, whereas the N-methyl-N-(3-chloropropyl)amine 3 cyclized slowly (t1/2 = 436 min) and was not tremorogenic by either route of administration. The N-methyl-N-(3-bromopropyl)amine 4(t1/2 = 11 min) and its iodo analogue 5 (t1/2 = 14 min) were quite potent in eliciting central muscarinic effects on both iv and ip injection to mice. It is concluded that haloalkylamine analogues of oxotremorine may serve in vivo as prodrugs for potent quaternary ammonium salts and that they are capable of circumventing the blood-brain barrier to such salts.