噻庚啶药理作用研究进展

噻庚啶药理作用研究进展张庆柱，张春芬（山东济宁医学院药理教研室，济宁２７２１１３）中文图书资料分类法分类号Ｒ９７１．９噻庚啶（Ｃｙｐｒｏｈｅｐｔａｄｉｎｅ，ＣＰＨ）是一哌啶化合物，既阻断组胺Ｈ１受体，又拮抗５－ＨＴＳ２受体（较大剂量也拮抗Ｓ１受体），...     

噻庚啶的抗心律失常作用和对心肌代谢的影响

在结扎大鼠左冠状动脉主支５ｍｉｎ．再灌注１５ｍｉｎ造成的再灌心律失常模型中．噻庚啶（Ｃｙｐ．４ｍｇ·ｋｇ－１，ｉｖ）明显降低再灌心律失常发生率，消除再灌引起的心室纤颤和室性心动过速．显著减少室性早搏个数．明显减慢心率．显著降低Ⅱ导ＥＣＧ的Ｐ波和Ｔ波电压．防止缺血所致ＳＴ段抬高。在离体灌流大鼠心脏心肌缺血再灌损伤模型中．Ｃｙｐ显著降低再灌心肌Ｃａ２＋聚积，有效防止Ｋ＋丢失．显著提高能量负荷（ＥＣ）．轻度提高腺苷三磷酸（ＡＴＰ）水平．显著降低腺苷一磷酸（ＡＭＰ）及次黄嘌呤核苷（ＩＮＯ）含量。表明：Ｃｙｐ有显著抗缺血再灌心律失常作用。并有拮抗钙．减轻Ｋ＋丢失和改善缺血再灌注心肌能量代谢作用。     

噻庚啶对失血性休克兔血浆SOD活性和MDA含量的影响

３０只兔随机分为噻庚啶治疗组和空白对照各１５只。颈动脉放血至血压５．３ｋＰａ，维持９０ｍｉｎ，复制失血性休克模型。于输血输液（对照组）和给药（噻庚啶１０ｍｇ／ｋｇ）后３０ｍｉｎ分别由颈动脉采取血样，测定血浆ＳＯＤ活性和血清ＭＤＡ含量。结果显示，噻庚啶明显地升高ＳＯＤ活性（Ｐ＜０．０１），降低ＭＤＡ含量（Ｐ＜０．０１）。氧自由基在休克的发生发展过程中起着重要作用，噻庚啶能够清除氧自由基，进而减轻细胞     

博利康尼噻庚啶治疗咳嗽变异性哮喘38例

我科1996年元月-1998年4月用博利康尼和噻庚啶联合治疗咳嗽变异性哮喘38例．取得满意疗效，现分析如下。     

噻庚啶对出血性休克兔血浆血栓素B2和6—酮前列腺素F1α的影响

２６只兔被随机分为治疗组和对照组：致动脉放血至血压５．３ｋＰａ，维持９０ｍｉｎ，复制出血性休克模型。于休克前后，输液输血（对照组）和给药（治疗组，噻庚啶１０ｍｇ·ｋｇ＾－１）后３０ｍｉｎ分别由颈动脉采取血样，结果显示用药组血栓素Ｂ２显下降（Ｐ＜０．０５），６－酮前列腺素Ｆ１α升高不明显（Ｐ＞０．０５）。噻庚啶致血浆血栓素Ｂ２水平下降是其抗休克作用机制之一。     

噻庚啶对失血性休克兔血浆SOD活性和MDA含量的影响

30只免随机分为噻庚啶治疗组和空白对照组各15只。颈动脉放血至血压5.3kPa,维持90min,复制失血性休克模型。于输血输液(对照组)和给药(噻庚啶10mg/kg)后30min分别由颈动脉采取血样,测定血SOD活性和血清MDA含量。结果显示,噻庚啶明显地升高SOD活性(P<0.01),降低MDA含量(P<0.01)。氧自由基在休克的发生发展过程中起着重要作用,巴庚啶能够清除氧自由基,进而减轻细胞损伤和多器官功能衰竭,是其抗休克作用机理之一。     

噻庚啶对失血性休克兔血浆SOD活性和MDA含量的影响

３０只免随机分为噻庚啶治疗组和空白对照组各１５只。颈动脉放血至血压５．３ｋＰａ,维持９０ｍｉｎ,复制失血性休克模型。于输血输液（对照组）和给药（噻庚啶１０ｍｇ／ｋｇ）后３０ｍｉｎ分别由颈动脉采取血样,测定血ＳＯＤ活性和血清ＭＤＡ含量。结果显示,噻庚啶明显地升高ＳＯＤ活性（Ｐ＜０．０１）,降低ＭＤＡ含量（Ｐ＜０．０１）。氧自由基在休克的发生发展过程中起着重要作用,巴庚啶能够清除氧自由基,进而减轻细胞损伤和多器官功能衰竭,是其抗休克作用机理之一。     

地塞米松,噻庚啶,山莨菪碱和地诺前列酮对内毒素休克TNFα产？…

目的：研究地塞米松（Ｄｅｘ）噻庚啶（Ｃｙｐ）,山莨菪碱（Ａｎｉ）和地诺前列腺酮（Ｄｉｎ）对脂多糖（ＬＰＳ）诱导的肿瘤坏死因子（ＴＮＦα）,基因表达的影响和抑制ＴＮＦ,产生的抗体休克作用。方法：Ｗｉｓｔａｒ大鼠静脉注射ＬＰＳ（ＥｃｏｌｉＯ１１１Ｂ４,５ｍｇ．ｋｇ＾－１）复制内毒素休克模型,Ｎｏｒｔｈｅｒｎ印迹杂交分析肝脏ＴＮＦαｍＲＮＡ表达,放射免疫法测定血浆ＴＮＦα的含量。结果：ＬＰＳ攻击后２ｈ肝     

噻庚啶与通窍活血汤治疗血管神经性头痛体会

血管神经性头痛是一种常见病，多发病，病因不明确，发病机制复杂，一般性治疗往往疗效不确切，笔者应用噻庚啶与中药汤剂通窍活血汤治疗血管神经性头痛，疗效颇佳，现总结如下。 1 临床资料 1.1 病例组成 本文病例均为1997~2001年门诊及部分住院患者，诊断标准参照1988年国际头痛分类。常规内科及神经科检查，排除其它疾病，有典型血管神经性头痛发作者为治疗对象。入选患者100例，其中男18例，女82例。发病年龄平均38.2岁，以中青年为多。将本组资料随机分成两组：观察组50例，对照组50例。 1.2 治疗方法 对照组常规治疗，观察治疗组…     

Analgesic antipyretic drugs as antagonists of bradykinin

The antagonism between analgesic antipyretic drugs and bradykinin was examined quantitatively, using the bronchoconstrictor response of guinea-pigs in vivo. The dose of bradykinin required to overcome antagonism by calcium acetylsalicylate increased with the dose of acetylsalicylate given, the ratio being roughly constant. Fifty times the quantity of acetylsalicylate which just antagonized bradykinin did not modify bronchoconstriction due to small doses of histamine, 5-hydroxytryptamine, or acetylcholine. A method of measuring the potency of this anti-bradykinin action was developed. Acetylsalicylic acid, phenylbutazone, amidopyrine, and phenazone had a high potency; paracetamol, cinchophen, sodium salicylate, and acetanilide had a moderate potency; and phenacetin, salicylamide, and 4-hydroxyisophthalic acid had little or none. Cortisone, hydrocortisone, aldosterone, amodiaquine, and morphine were ineffective or their action was non-specific. In sensitized guinea-pigs, an injection of antigen caused bronchospasm. This response was greatly lessened by pretreatment with mepyramine, but was not affected by calcium acetylsalicylate, lysergic acid diethylamide, or atropine. Acetylsalicylic acid, phenylbutazone, and amidopyrine did not specifically antagonize the action of bradykinin on the capillaries of guinea-pig skin in vivo, on guinea-pig ileum in vitro or on rat duodenum in vitro.     

Analgesic,antipyretic, anti-inflammatory and toxic effects of andrographolide derivatives in experimental animals

Andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (2) are active constituents of Andrographis paniculata (Burm. f.), family Acanthaceae. A. paniculata extracts are reported to have antiviral, antipyretic, immunostimulant and anticancer activities. In this study, 1 and its 14-acetyl- (4) and 3,19-isopropylidenyl- (3) derivatives, as well as 2 and its 3,19-dipalmitoyl-derivative (5), were intraperitoneally tested for their analgesic, antipyretic, anti-inflammatory and acute toxicity effects in animal models. Analgesic effects were tested in mice using hot plate and writhing tests to distinguish the central and peripheral effects, respectively. The results showed that, at 4 mg/kg, all tested substances have significant analgesic effects, and the highest potency was seen with 3, 4 and 5. Increasing the dose of 3 and 5 to 8 mg/kg did not increase the analgesic effect. In the writhing test, 3 and 5, but not 1, showed significant results. In a baker’s yeast-induced fever model, 3 and 5 significantly reduced rats’ rectal temperature (p < 0.05). In a carrageenan-induced inflammation model, 1, 3 and 5 significantly reduced rats’ paw volume. Doses of 3 and 5 up to 100 mg/kg did not show any serious toxic effects. From this study, 3 and 5 are the most interesting derivatives, showing much greater potency than their parent compounds. These could be further developed as analgesic, antipyretic and anti-inflammatory agents, without any serious toxicity.     

Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta

Lyophilised aqueous extract of Euphorbia hirta L. (Euphorbiaceae) has been evaluated for analgesic, antipyretic and anti-inflammatory properties in mice and rats, in order to complete its activity profile, after the confirmation of the existence of a central depressant activity particularly expressed by a strong sedative effect, associated with anxiolytic effects. This study leads us to the conclusion that this plant extract exerts central analgesic properties. Such a dose-dependent action was obtained against chemical (writhing test) and thermic (hot plate test) stimuli, respectively, from the doses of 20 and 25 mg/kg and it was inhibited by a naloxone pretreatment, a specific morphinic antagonist compound. An antipyretic activity was obtained at the sedative doses of 100 and 400 mg/kg, on the yeast-induced hyperthermia. Finally, significant and dose-dependent anti-inflammatory effects were observed on an acute inflammatory process (carrageenan-induced edema test in rats) from the dose of 100 mg/kg. On the other hand, plant extract remained inactive on chronic processes such as Freund's adjuvant-induced rheumatoid arthritis, after a chronic treatment during fourteen days at the daily dose of 200 or 400 mg/kg; however, if inefficacy was observed on rat backpaws edema and on loss of weight, the aqueous extract reduced the inflammatory hyperalgia.     

Analgesic and antipyretic activities of Rumex patientia extract on mice and rabbits.

The aqueous extract from the roots of Rumex patientia L. (Polygonaceae) was investigated for its analgesic and antipyretic effects on mice and rabbits. When the activities of the extract were evaluated in comparison with acetylsalicylic acid (ASA), indomethacin and morphin, it was found to possess significant analgesic and antipyretic activities.     

Pharmacological studies on proglumetacin maleate, a new non-steroidal anti-inflammatory drug. (2). Analgesic and antipyretic effects

Analgesic and antipyretic effects of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were investigated in comparison with those of IND on an equimolar-dose basis. The suppression of phenylquinone-induced writhing in mice by PGM was about 0.8 and 2 times as potent as that by IND when given 1 and 4 hr before the phenylquinone injection, respectively. The analgesic activity of PGM in rat silver nitrate arthritis was about 1.5 times more potent than that of IND. PGM was slightly less active in rat adjuvant arthritic pain than IND. On the other hand, PGM provoked a dose-dependent antipyretic effect on the yeast-induced fever in rats within the dose range without affecting the normal body temperature. Furthermore, PGM showed a significant antipyretic effect on LPS-febrile rabbits. Generally, the antipyretic effect of PGM was moderate as compared with that of IND. These analgesic and antipyretic actions of orally administered PGM may be mainly due to its active metabolite, IND. The above results indicate that PGM may be useful for inflammatory diseases associated with pain and/or fever.     

消炎退热颗粒清热解毒作用研究

目的：观察中成药消炎退热颗粒（DPZG）对家兔发热模型、小鼠急性耳廓肿胀模型、小鼠内毒素血症模型的作用,探讨其清热解毒的作用和机理。方法：采用脂多糖（lipopolysaccharides,LPS）耳缘静脉注射建立家兔发热模型,评价其解热作用;采用二甲苯致小鼠急性耳廓肿胀模型评价其抗炎作用;建立小鼠内毒素血症模型,观察DPZG对于D-氨基半乳糖（ACTD）敏化小鼠LPS致死攻击的影响,评价其抗内毒素的作用;以Elisa法检测DPZG对内毒素血症模型小鼠血清中TNF-α、IL-1β等炎症因子水平的影响,Western blot法检测小鼠肝、脾、肾组织中膜突蛋白（moesin）以及磷酸化P38 MAPK表达。结果：与模型组比较,DPZG对家兔体温升高有显著抑制作用,与阿司匹林趋同;可显著降低二甲苯致小鼠急性耳廓肿胀程度;可显著升高内毒素血症模型小鼠存活率;显著降低小鼠血清中TNF-α、IL-1β水平和小鼠肝脾肾组织内p-P38MAPK和膜突蛋白（moesin）的表达,效果明显优于中成药对照药蒲地蓝消炎口服液（PBKH）。结论：消炎退热颗粒有显著清热解毒作用,主要作用方式是解热、抗炎、抗内毒素,且效果明显优于PBKH。其作用机制可能与抑制IL-1β、TNF-α、Moesin以及p-P38 MAPK的表达有关。     

Analgesic,anti-inflammatory,and antipyretic activities of the ethanol extract from Desmodium caudatum

Context: In folk medicine in China, Desmodium caudatum (Thunb.) DC (Leguminosae) has been used to treat febrile diseases, rheumatic arthritis, and bacillary dysentery; nevertheless, there have been no reports on the analgesic, antipyretic, and anti-inflammatory effects of this plant in animals.

Objective: To investigate the analgesic, anti-inflammatory, and antipyretic activities of D. caudatum extract (DCE) in animals.

Materials and methods: The analgesic effect of DCE was measured in mice using the acetic acid-induced writhing test and the hot-plate test. The anti-inflammatory activity was assessed using the carrageenan-induced rat paw edema model and the dimethylbenzene-induced mouse inflammation model. The antipyretic effect was estimated using the lipopolysaccharide (LPS)-induced rat fever model. In addition, the acute oral toxicity of DCE was studied.

Results: DCE significantly and dose-dependently inhibited the writhing responses in mice, increased reaction time in mice in the hot-plate test, reduced carrageenan-induced paw edema in rats and the dimethylbenzene-induced ear edema in mice, and attenuated LPS-induced fever in rats. Furthermore, no death was observed when mice were orally administered DCE up to 40?g/kg.

Discussion and conclusion: DCE possesses evident analgesic, anti-inflammatory, and antipyretic activities, and has a favorable safety, which supports the use of D. caudatum as an analgesic, anti-inflammatory and antipyretic drug in folk medicine.