汉防己甲素及乙素降压的机制

1.甲素及乙素預先作靜脉注射,能使乙醯胆硷的降压作用加强及作用时間延長,同时阿託品可部分取消甲素及乙素的降压作用,可以認为其有拟似胆硷反应系統(M-系統)的作用。2.甲素及乙素对腎上腺素之升压作用並無影响。3.甲素及乙素对交感神經节並無阻断作用,相反,当甲素及乙素产生显著血压下降时,往往引起交感神經节的短暫兴奋現象。4.甲素及乙素可取消或減弱因压迫頸动脉所引起的升压反射,二者的降压作用並不受切断二侧竇神經所影响,可以推想其对血管运动中樞或交感神經中樞有抑制作用。5.甲素及乙素对血管的直接及反射性舒張作用,对血管运动中樞或交感中樞之抑制及对胆硷反应系統的拟似作用等,应可視为它們降压作用之主要机制。6.甲素及乙素之药理性質相似,但乙素之降压作用較甲素为弱且易产生急速耐受現象。     

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。     

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。     

国产乙酰普马嗪的药理作用研究——加强作用及对交感神经末梢介质释放的影响

(1)采用热水刺激小白鼠尾巴法試驗鎮痛作用,乙酰普馬嗪0.5毫克/公斤可使“疼痛”反应出現时間延迟,較盐酸嗎啡(2毫克/公斤)为弱;二者均以半量合并应用,鎮痛作用强度虽未見加强,但鎮痛时間則延长。(2)脑室內注射乙鮂振R嗪,可立即引起小白鼠安靜,并使其体溫明显下降;皮下注射同剂量时,安靜及降溫作用均不显著,但可明显加强安替比林及水合氯醛的降溫作用。(3)乙酰普馬嗪局部滴药及皮下注射均可产生角膜麻醉,并可加强普魯卡因的表面麻醉作用,尤以皮下注射法为强。(4)乙酰普馬嗪2.5微克/公斤即可減弱腎上腺素的升压作用;5微克/公斤时,使后者作用翻轉,并使电刺激交感神經节前纤維及注射腎上腺素所引起的瞬膜收縮反应減弱。(5)在离体兔神經——迴腸标本,电刺激交感神經节后纤維引起腸张力下降,运动減弱,乙酰普馬嗪及氯丙嗪均可加强此交感反应。     

维生素C对大白鼠条件反射活动的影响

利用大白鼠运动防御性条件反射方法,研究了大剂量維生素C对健康动物高級神經活动的影响。結果証明,每日腹腔注射維生素C 0.2克/公斤能加速大白鼠阳性条件反射的形成。維生素C 0.1—1克/公斤可使大白鼠阳性条件反射潛伏期縮短,靜脉給药較腹腔給药效果显著。腹腔注射維生素C 0.2克/公斤与咖啡因(25毫克/公斤,皮下注射)并用对条件反射无明显协同作用;与氯丙嗪(3毫克/公斤,腹腔注射)并用有一定拮抗作用。当靜脉注射維生素C 0.2/公斤时,对氯丙嗪有明显的拮抗作用。腹腔注射維生紊C 0.4克/公斤对消退性抑制,以及靜脉注射維生素C 0.1克/公斤对分化性抑制皆无显著影响。     

广地龙中促进子宫收缩的成分

本文研究了自广地龙中提出来的一种引湿性、淡黄色針状結晶(含量約0.2%)对平滑肌器官(特别是对子宮)的作用。介紹了該結晶的提取方法。該結晶0.1毫克加入25毫升Locke液中,能使已孕和未孕大鼠或豚鼠离体子宮角紧张度明显升高,0.3毫克可使之呈痙攣收縮状态。按1毫克/公斤給已孕和未孕麻醉家兔靜脉注射后15—30分钟,在位子宮紧张度升高,作用維持1.5—3小时。按8—10毫克/公斤注射,子宮紧张度立卽升高和血压急剧下降到零而死亡。9只慢性子宫瘻家兔靜脉注射(3—6毫克/公斤)或灌胃給药(10—20毫克/公斤)后15—45分钟,子宮收縮明显增强,作用維持1.5—3小时(注射給药)和7小时以上(灌胃給药)。多数实驗家兔在子宮兴奋同时有排便現象。該結晶对家兔在位腸管和大鼠后肢血管均有强烈兴奋作用,但对豚鼠支气管肌作用极弱。当給小鼠靜脉注射时,LD₅₀为38.7毫克/公斤。     

狭叶萝芙木根生物碱的降压作用及机制

继中国蘿芙木之后,最近在云南又发現狹叶蘿芙木(Rauwolfia yunnanensis Tsiang var.angustifolia C.Y.Wu.)。其根生物碱对麻醉动物具降压作用,給犬靜脉注射1毫克/公斤后2小时內的降压面积为-32%,給猫靜脉注射3毫克/公斤的降压面积为-30%。同时測得中国蘿芙木根生物碱在犬的降压面积为-45%,猫为-29%。重复給药有快速耐受性。降压的同时呼吸呈兴奋,对心率影响不明显。降压作用与M-胆碱能反应系統、N-胆碱能反应系統以及內感受器都无关系?匝芤参拗苯幼饔?单側頸交感神經切除兔耳試驗发現,扩张血管的作用与交感神經有关。狹叶蘿芙木根生物碱可抑制腎上腺素或去甲腎上腺素的加压反应,也可抑制阻断頸总动脉血流和电刺激迷走神經或胫骨神經中枢端所致的加压反射。用脊猫試驗吋其降压作用大为減弱,但并不完全消除,降压面积仅为-14%。因此,其降压机制包括中枢和外周两方面,即对血管运动中枢的抑制作用和抗腎上腺素的作用。急性毒性試驗証明,狹叶蘿芙木根生物碱的毒性很小,小鼠口服2000毫克/公斤无死亡发生,动物呈現安靜状态。     

延胡索的药理研究(Ⅳ)延胡索素乙和丑对循环和呼吸的影响

1.給麻醉猫靜脉內慢慢注射延胡索素乙40毫克/千克(相当2倍鎮痛有效剂量)时,血压略降,心跳变慢,心脏功能無明显变化.正常家兔靜脉注射乙素20或40毫克/千克时,呼吸短时兴奋;剂量增至60毫克/千克(相当3倍鎮痛有效剂量)时,呼吸有抑制. 2.麻醉猫靜脉內慢慢注射延胡索素丑30毫克/千克(相当鎮痛有效剂量的2倍),血压略降,心跳变慢,心电圖的T波有倒置現象。正常家兎靜脉注射丑素30毫克/千克时,对呼吸無抑制,而有兴奋現象。     

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。     

广地龙的降压作用和降压机制的探讨

本文对广地龙毒性、降压作用和降压机制作了初步探討。广地龙热浸剂给小鼠靜脉注射时,LD₅₀=38.5克/公斤。热浸剂(0.1克/公斤)連續給大鼠灌胃45天,未发現毒性反应。給麻醉狗按0.1克/公斤靜脉注射热浸剂或乙醇浸出液,在給药30—45分钟出現血压下降,一般可維持2—3小时。正常大鼠一次用大剂量(10克/公斤)灌胃或腎型高血压大鼠用个剂量(50毫克/公斤)长时間(2周)灌胃,均有明显的降血压作用。在后一种情况下,多数大鼠血压下降出現于給药的第3—7天,并于停药后第2周回升到用药前水平。广地龙降压机制可能是由于它直接作用于脊髓以上的中枢神經系統或通过某些內感受器反射地影响中枢神經系統,引起部分內脏血管的扩张而使血压下降。     

云南萝芙木的药理研究,—云南萝芙木的降压作用及其机制

自从夹竹桃科植物印度蛇木(Rauwolfia Serpentina Benth.)的各种制剂(特别是Reserpine)对高血压的疗效引起全世界医、药学家的重视后,我国学者也从本国寻找其代替品,并在云南、广东、广西及海南岛找到了同属植物蘿芙木R. Verticillata (Lour.) Baill.李承祜等及云南药用植物研究所曾做过其生药学的研究。赵承嘏等曾从广东蘿芙木提出一种生物硷,名为蘿芙甲素(Rauwolfia A),经夏炳南等,林吉强等进行了药理研     

防己生物碱的毒性及降压作用

正常狗2只,以防己生物碱連日給药,最高一次灌胃量达160毫克/公斤,为降压有效量16倍,无急性不良反应发生,服药过程中体重、食量及外表皆无明显改变。实驗治疗的3只高血压皮桥狗,无論心电图、血清磺溴酞鈉存留率及全血非蛋白氮含量皆属正常;但个別狗首次給药曾发生特异反应,大剂量长期給药可使全血非蛋白氮含量稍高,临床試用尚宜适当注意。总碱对麻醉或不麻醉实驗动物无論靜脉注射或灌胃都有肯定的急性降压效果,其作用特点为降压迅速、显著,持續时間約2—4小时,連續多次給药有快速耐受現象。对慢性实驗治疗狗的疗效不著,可能与其作用特点有关,可考虑与作用緩慢而持久的降压药合并应用。总碱的降压与其抗腎上腺素作用及神經反射机制有关。总碱无阻断神經节作用,其降压与M-胆碱反应系統无关,也非組織胺释放所致。在本实驗条件下未見总碱有直接扩张血管的作用。靜脉注射1—2毫克/公斤,对麻醉狗的心輸出量有抑制性影响,总外周阻力的降低不明显。     

Cardiovascular effects of a novel calcium entry blocking and selective beta 1-adrenoceptor blocking agent, YM-16151-4, in anesthetized and conscious dogs.

Cardiovascular effects of YM-16151-4, a combined calcium entry blocking and beta 1-adrenoceptor blocking agent, were evaluated in dogs. In anesthetized dogs, YM-16151-4 (0.01-1 mg/kg intravenously, i.v.) dose-dependently increased coronary blood flow (CBF) and decreased mean blood pressure (MBP), total peripheral resistance (TPR), dP/dtmax, double product, and left ventricular (LV) work without increasing heart rate (HR) and cardiac output (CO). YM-16151-4 increased vertebral blood flow as well as CBF, but had no effect on carotid, mesenteric, renal, and femoral blood flow. Coronary vasodilating activity of YM-16151-4 was also observed after intracoronary artery injection (i.a.). In anesthetized and vagotomized dogs, YM-16151-4 dose-dependently inhibited isoproterenol (0.2 micrograms/kg i.v.)-induced tachycardia and decrease in diastolic BP (DBP), with ED50 values of 0.039 and 0.52 mg/kg i.v., respectively. In conscious dogs, YM-16151-4 (0.1-1 mg/kg i.v.) produced a dose-dependent hypotensive effect with no effect on HR or PQ-interval. The hypotensive effect of YM-16151-4 (0.3 and 1 mg/kg i.v.) reached its maximum approximately 1-2 h after each dosing and lasted 6-8 h. These results suggest that YM-16151-4 actually behaves as a hybrid compound, combining calcium entry blocking and beta 1-adrenoceptor blocking activities, and that this compound could be a novel long-acting antianginal and antihypertensive agent.     

Antihypertensive effect of betaxolol, a cardioselective beta-adrenoceptor antagonist, in renal hypertensive dogs

The antihypertensive effect of betaxolol, a highly selective beta 1-adrenoceptor antagonist, was investigated in renal hypertensive dogs, and the mechanism was also studied. A single oral administration of betaxolol (1 and 10 mg/kg) lowered blood pressure dose-dependently. The hypotensive effect of betaxolol was enhanced by daily oral administration for 10 days. In anesthetized dogs, intraarterial injection of betaxolol produced a dose-dependent increase in femoral artery flow; and in this test, betaxolol was 3 times less potent than papaverine. The increase in blood flow with betaxolol was not affected by pretreatment with propranolol. These findings indicate that a certain vasodilating activity may contribute to the antihypertensive mechanism of betaxolol.     

大量抗坏血酸注射液对心血管系统的作用

本文报导大量抗坏血酸注射液(injectio acidi ascorbici,以下簡称IAA)对动物血压、心脏及血管的影响。IAA为用碳酸氫鈉中和的10%抗坏血酸灭菌溶液,pH約为5.6,內加焦亚硫酸鈉作稳定剂。靜脉注射IAA 0.2克/公斤及0.4克/公斤可使麻醉犬、猫和家冤动脉血压輕度短时上升;在因手术創伤、失血及数种降压莉物(氯丙嗪、亚硝酸鈉、組織胺、罌粟碱)所致低血压的动物,IAA的升压作用較为明显持久。同剂量抗坏血酸溶液(solution acidiascorbici,以下簡称SAA)靜脉注射常引起血压下降,用碳酸氫鈉将SAA中和后即有升压作用,焦亚硫酸鈉无升压作用,故IAA的升压作用是中和后的抗坏血酸所引起。靜脉注射IAA0.2克/公斤可增加麻醉犬心搏量、心輸出量及心脏指数,对总外周阻力无明显影响;对在体冤心亦呈現兴奋作用。1:1,000和1:500的IAA灌流离体冤心后,可見心縮振幅加大,心率略增,冠脉流量增多。IAA对离体冤耳、腎、下肢血管无明显影响。在体冤下肢及腎血管血流量在血压上升时均有增加。犬脾容积在IAA注射后有輕度扩张現象,而SAA却使脾容积短时減少。实驗結果表明,IAA的升压作用主要是由于心脏功能改善,心輸出量增加所致。     

Pharmacological analysis of the mode of action of mandelamidine with sustained antihypertensive effect. (II). Mechanism of transient hypotensive action of mandelamidine]

The mode of a transient hypotensive action of dl-Mandelamidine (MA) was studied in both anesthetized and unanesthetized animals. In the blood pressure of unanesthetized rats, a transient hypotensive action of MA (1 approximately 30 mg/kg i.v.) like papaverine (1 approximately 10 mg/kg i.v.) was much less predominant than in rats anesthetized with urethane (1.5 g/kg s.c.). The transient hypotensive action of MA (10 mg/kg i.v.) in rats anesthetized with urethane (1.5 g/kg s.c.) was not reduced when MA was injected continuously. Moreover C6 (5 mg/kg i.v.), propranolol (1 mg/kg i.v.), diphenhydramine (10 mg/kg i.v.) and atropine (2 mg/kg i.v.) did not block this transient hypotensive action. MA blocked the pressor action of epinephrine (3 mug/kg i.v.) in three minutes, but then potentiated it. MA (10 mug/kg i.a. approximately 1 mg/kg i.a.) caused a temporary vasodilation on the perfused leg artery and vertebral artery in dogs anesthetized with sodium pentobarbital (30 mg/kg i.v.). In the perfused leg artery, atropine (2 mg/kg i.v.) and propranolol (1 mg/kg i.v.) did not block the vasodilation of MA, and MA showed no marked blocking effect of the vasoconstriction of norepinephrine (0.2 mug/kg i.a.). In the dog heart-lung preparation and the guinea-pig heart, MA showed inhibiting effects. On the contraction of the cat nictitating membrane elicited by the stimulation of the postganglionic cervical sympathetic nerve, the blocking action of MA (1 mug/kg i.a. approximately 1 mg/kg i.a.) was much less predominant than that of phentolamine (10 mug/kg i.a.). In the rabbit descending aorta, MA (3 X 10(-4) g/ml) antagonized non-competitively the contraction elicited by norepinephrine. These findings suggest that a transient hypotensive action of MA depends upon the inhibiting effects on the cardiovascular system, and the adrenergic alpha-blocking effect of MA may be very weak.     

甲基莲心碱对正常及高血压大鼠血流动力学的影响

iv甲基莲心碱(Nef)6 mg/kg于正常血压、肾性高血压、DOCA盐型高血压大鼠,在血压下降的同时,伴有LVSP,±(dp/dt)max,(dp/dt)P~(-1)的降低,正常血压及肾性高血压大鼠LVSP~-(dp/dt)P~(-1)环缩小,其斜率变小,心率短时变慢,LVEDP变化不明显。iv Nef 2 mg/kg于Wistar高血压大鼠时,仅明显降低血压,而对其它血流动力学指标无明显影响,Nef降低舒张压的作用大于降低收缩压。猫后肢灌流实验证明Nef有明显降低血管阻力的作用。结果表明Nef的降压作用可能由于扩张外周血管所致。     

碘化二甲基木防己的降压作用

本文报告碘化二甲基木防己碱(DTI)降压作用的研究。DTI给麻醉动物静脉注射,对狗0.05～0.1 mg/kg使血压下降42.3～61.5%,持续1小时左右恢复至原血压水平;对猫0.00625～0.0125 mg/kg使血压下降26.5～43.5%,持续2～4小时恢复至原血压水平;对兔0.005～0.01 mg/kg使血压下降24.3～61.0%,5小时不能恢复至原血压水平;0.5～1.0 mg/kg使大鼠血压下降27.2～41.1%。DTI的降压作用机制主要与其对神经节的阻断作用有关。本药对小鼠口服和静注的LD₅₀分别为522.0 mg/kg及2.23 mg/kg。     

Hypotensive effect and toxicity of octadin and papaverine following their combined administration]

A study on the hypotensive action of combined injections of papaverine and octadine (guanethidine) was carried out in acute experiments on 90 anaesthetized cats. It was shown that with combined injections of octadine (in doses exceeding by 22% ED100) and of papaverine (in doses inferior by 22% to ED100) the hypotensive action was potentiated. A change of the said proportions led to a diminished hypotensive effect. It was also found that the most effective combinations of the 2 drugs was the one consisting of 0.5 mg/kg of papaverine and 5 mg/kg of octadine (in a ratio of 1:10). By studying the toxicity of the 2 drugs and of their combinations on 350 albino mice it was ascertained that their toxicity diminished if the drugs were used together.