西尼地平的合成工艺改进

目的改进二氢吡啶类钙拮抗剂西尼地平的合成工艺。方法以肉桂醇为原料,经酯化、氨化和缩合-环合而得。结果所得产物结构经红外光谱、核磁共振氢谱及质谱确证,总收率57.3%。结论改进后的合成工艺简单、合理可行。     

西尼地平的抗高血压作用及交感神经抑制活性

目的 介绍西尼地平的临床前药理研究及临床应用。方法 检索Medline，查找原。结果 西尼地平不仅能阻滞血管平滑肌上的L-型Ca^2 通道，还能阻滞交感神经元上的N-型Ca^2 通道。西尼地平无降压所导致的反射性交感神经兴奋，对原发性高血压病人能有效降压，且不引起心率加快。结论 西尼地平可能会成为新一代抗高血压的典型药物。     

西尼地平与尼群地平治疗高血压病的疗效比较

目的:比较西尼地平与尼群地平治疗高血压病的疗效及安全性。方法:86例原发性高血压病患者随机均分为西尼地平组和尼群地平组,西尼地平组给予西尼地平,起始剂量为5mg,qd,根据血压可调整至10mg,qd;尼群地平组给予尼群地平,起始剂量为10mg,qd,根据血压可调整至20mg,bid。比较2组的降压疗效及药品不良反应。结果:西尼地平组与尼群地平组的总有效率分别为90.7%和88.4%,2组比较差异无统计学意义(P>0.05);西尼地平组和尼群地平组收缩压的最大降幅分别为(34.2±3.8)和(29.2±2.2)mmHg,舒张压最大降幅分别为(23.8±2.6)和(19.4±2.3)mmHg,差异有统计学意义(P<0.05)。尼群地平组治疗后心率明显快于治疗前及西尼地平组治疗后(P<0.05),但西尼地平组患者心率治疗前、后无显著变化(P>0.05)。治疗过程中2组均未见明显不良反应发生。结论:西尼地平用于治疗高血压疗效与尼群地平相近,但其对患者的心率影响较小。     

西尼地平的合成

以双烯酮为原料，分别与乙二醇单甲醚和肉桂醇进行酯化反应制得乙酰乙酸-2-甲氧基乙酯和乙酰乙酸肉桂酯，前者与间硝基苯甲醛缩合生成的2-（3-硝基亚苄基）乙酰乙酸2-甲氧基乙酸和后者的氨化产物3-氨基-2-丁烯酸肉桂酯再进行Hantzsch环化反应制得新型钙拮抗剂西尼地平。方法条件温和，反应总收率68.3%(以肉桂酯计）。     

西尼地平片治疗轻中度高血压的有效性和安全性

目的评价西尼地平治疗轻中度原发性高血压的有效性和安全性。方法用随机双盲对照试验设计,入选病人共48例,西尼地平(试验组)24例,氨氯地平(对照组)24例。结果与治疗前相比,治疗8周后试验组收缩压和舒张压分别下降19.26和14.68mmHg(P<0.01),对照组分别下降为18.22和12.91mmHg(P<0.01),均有统计学意义。试验组和对照组药物不良反应的例数分别为0和2例,2组比较无统计学差异(P>0.05),均无严重不良反应发生。结论西尼地平片每日服用1次,降低血压,安全有效。     

国产西尼地平治疗轻中度高血压有效性及安全性研究

目的 评价国产西尼地平治疗轻度至中度高血压的临床疗效及安全性。方法 以国产马来酸氨氯地平为对照药，在轻度至中度高血压病人中进行多中心、随机、双盲、平行、活性对照的临床试验。结果 西尼地平组平均坐位收缩压下降17．48mmHg(2．33kPa)(-11．58％)，舒张压下降14.46mmHg(1．93kPa)(-14．6l％)。有69例(65．09％)患者在治疗结束时达到方案规定的治疗显效标准，15例(14．15％)患者达到有效标准，总有效率为79．24。在安全性/耐受性方面，西尼地平组内出现12例次考虑与治疗相关的不良事件，主要为心悸、头晕和面色潮红。没有出现有临床意义的生化及心电图改变。结论 国产西尼地平片疗效肯定，耐受性好，副作用少。     

西尼地平治疗原发性轻中度高血压25例

目的评价西尼地平治疗轻、中度原发性高血压患者的疗效和安全性。方法采用随机双盲对照试验设计，将轻、中度原发性高血压患者50例随机分为治疗组和对照组各25例，分别给予西尼地平和氨氯地平，起始剂量均为5 mg，qd，po。治疗4周后未达到有效标准则药物剂量加倍，继续治疗4周；有效者则维持原先剂量继续服用4周。结果治疗8周后，治疗组收缩压和舒张压分别下降（18.28±9.03），（12.96±4.33）mmHg（P＜0.01），对照组分别下降（19.24±10.30），（14.68±6.10） mmHg（P＜0.01）。治疗组和对照组药物不良反应的例数分别为1和2例，两组血压下降幅度及不良反应比较均差异无显著性（P＞0.05）。试验过程中不良反应均能耐受。 结论西尼地平治疗轻中度高血压有效，安全。     

西尼地平的光稳定性试验研究

目的 研究西尼地平的光稳定性。方法以西尼地平原料、西尼地平甲醇溶液、西尼地平片剂溶出液为对象，分别用强光(4500lx)或自然光照射，用HPLC法测定光照射后的降解产物，以卯LC-MS研究光降解产物的结构，并研究自然光对片剂溶出度测定的影响。结果西尼地平原料、西尼地平甲醇溶液对光敏感，在强光(4500lx)照射下分解生成Z-异构体。自然光可影响西尼地平片剂的溶出度测定，在不避光时西尼地平片剂溶出液吸收度下降，溶出度测定结果偏低。结论西尼地平对光敏感，西尼地平及其制剂均应该避光保存，西尼地平制剂的溶出度测定时应注意避光操作。     

西尼地平治疗轻中度原发性高血压的疗效观察

目的探讨西尼地平治疗轻中度原发性高血压的临床疗效与安全性。方法 将原发性高血压患者98例随机分为治疗组49例和对照组49例,治疗组给予西尼地平治疗,起始剂量为5mg,每天1次,若4周后未达到目标血压,则剂量增加为10mg,有效者则维持原先剂量服用至诊疗结束;对照组给予苯磺酸氨氯地平治疗,服药时间、用法同治疗组。对比2组临床疗效、治疗前后血压及不良反应。结果 治疗组总有效率为93.88%,对照组总有效率为91.84%,2组比较差异无统计学意义（P〉0.05）。经8周治疗后2组血压均有所下降（P〈0.05）,血压下降值差异无统计学意义（P〉0.05）;且均无明显不良反应。结论 西尼地平能够有效地降低患者的血压,不良反应少,疗效显著,适用于治疗原发性高血压。     

Pharmacological study of cantharidin-induced ear inflammation in mice

Cantharidin applied to the Swiss mouse ear induced a clearly observable inflammatory reaction after 6 hr, maximal after 24 hr, and persisting several days. Desonide and hydrocortisone strongly inhibited the acute (6 hr) and delayed (24 hr) phases after their local application, while, after oral treatment, a reduction in the acute edema was obtained only when using high doses. The cutaneous application of high doses of mepyramine, disodium cromoglycate, methysergide, and (at a quite lower level) cimetidine reduced the 6-hr inflammation. Phenylbutazone and acetylsalicylic acid showed little activity on the same phase after their cutaneous administration. All the nonsteroid compounds produced little or no effect on the 24-hr inflammation after their cutaneous application and were quite inactive on both phases after their systemic treatment. The cantharidin-induced inflammatory reaction in Swiss mouse seems thus to be characterized by two phases. The chronic delayed phase is an example of chronic inflammation without the involvement of immunological processes. Histamine and serotonin might be involved in the acute inflammation.     

解酒饮的药理学研究

目的:研究解酒饮的解酒作用.方法:40只小鼠随机分成空白对照组,胆维他对照组(25mg·g-1)和高低剂量解酒饮组(25,12.5g·kg-1).用自制30%白酒按14mL·kg-1灌胃造成小白鼠醉酒模型,分别在造模前后单次给药,观察小白鼠翻正反射消失的时间和小鼠酒醉持续时间.结果:与空白对照组比较,解酒饮25g·kg-1组小鼠翻正反射消失时间显著延长,酒醉持续时间显著缩短.而解酒饮12.5g·kg-1组无显著性差异.结论:按生药25g·kg-1给予解酒饮,对于小白鼠具有预防醉酒和醒酒的作用.     

Radioautographic study on the distribution of oxypertine (Win 18,501) in mice and cats

Summary The distribution of i.v.-injected tritiated oxypertine was studied in mice and cats by an autoradiographic technique. The compound rapidly accumulated in the lung, kidney, liver, adrenal medulla and brain. Later on the radioactivity concentrated also in bone marrow, pancreas and salivary glands, and still more in the gall-bladder and gastro-intestinal contents. The adrenal medulla, liver and kidney retained their activity for a long time. The hippocampus, thalamus and cerebral cortex were the most active sites in the brain. Oxypertine passed the placental barrier and was found especially in the foetal membranes and placenta and in the liver and gut contents of the foetus.     

Pharmacological and biochemical studies in isolation-induced fighting mice

Summary Described herein is the effect of several drug classes on suppressing isolation-induced fighting behavior. A diverse group of drugs was found to have an inhibitory effect on this form of behavior. Also included is our method of assay adapted from the work of others in which training and isolation are combined to produce agonistic behavior. This increases the number of fighters. Isolation appeared to be more important than training in the development of fighting behavior under our conditions. Fewer animals developed fighting behavior in summer than in other seasons. No differences were found between fighters and non-fighters with regard to the serum corticosterone levels and the content of brain serotonin and norepinephrine.     

Pharmacological and histological characterisation of nicotine-kindled seizures in mice

The present study reports that it is possible to induce kindling by repeated injections of nicotine. The newly characterised nicotine-kindling model was compared with that of pentylenetetrazole (PTZ) kindling. Mice were kindled by repeated injection of PTZ (37 mg/kg), or nicotine (2.3 mg/kg), and the effect of the anti-epileptic drugs (AED) levetiracetam (LEV), tiagabine (TGB) and phenytoin (PHT) on seizures in kindled and naive mice were investigated. C-Fos immunoreactivity (Fos IR) was used to investigate differences in neuronal activity pattern between PTZ-, nicotine kindled and naive animals. PTZ kindled animals mainly showed increased Fos IR in limbic regions, whereas Fos IR in nicotine kindled animals was increased in the entorhinal cortex, medial habenula and the compact part of substantia nigra. Fully kindled PTZ-induced seizures were inhibited by LEV (ED50=13.6+/-7.8 mg/kg), TGB (ED50=0.3+/-0.04 mg/kg) but not PHT (ED50>40 mg/kg) whereas fully kindled nicotine-induced seizures were inhibited by LEV (ED50=1.4+/-0.4 mg/kg), TGB (ED50=0.3+/-0.06 mg/kg) and PHT (ED50=9.2+/-2.4 mg/kg). These differences in efficacy of AEDs were not due to changes in plasma levels in the various models. In conclusion, repeated administration of nicotine can induce a kindling-like phenomenon and the model showed significantly different Fos IR pattern and pharmacology to that of PTZ kindling.     

Pharmacological comparison of peristaltic effects in rats and mice

IntroductionConscious rodent models are commonly used to assess the effects of new chemical entities on propulsion (transit) time in the gastrointestinal system. This study was designed to compare three compounds clinically known to cause constipative (morphine sulfate and propantheline bromide) and laxative (metoclopramide hydrochloride) effects on transit time in rats and mice and to note if there are differences between the species.MethodsCompounds were dosed in conscious rats and mice. At 0.5–2.0 h post dosing (estimated time to maximal plasma concentration of each compound) animals were gavaged with an appropriate volume (based on weight) of 10% activated powdered carbon suspended in 5% gum arabic. Forty-five minutes following dosing the animals were sacrificed by CO₂ asphyxiation and the small intestine was removed. The position of the leading edge of the charcoal was measured relative to the total length of the intestinal segment.ResultsThe compounds tested produced variable statistical differences in transit time between species. Morphine and propantheline produced dose-dependent increases in transit time, and metoclopramide decreased transit time, statistically significant in both rodent models.DiscussionThe present data demonstrate that at similar doses rats and mice can be used interchangeably for transit studies. Mice were more sensitive to transit changes at higher doses of the compounds tested.     

Pharmacological studies on stimulation-produced analgesia in mice

Stimulation-produced analgesia (ESPA) was induced in mice by peripheral caudal electrostimulation and subsequently monitored on a 52 degrees C hot plate. The effects on ESPA of compounds modulating some neurotransmitter systems were studied at appropriate premedication times and at doses at which the compounds themselves did not exhibit antinociceptive actions. The manipulation of catecholaminergic, dopaminergic or GABAergic systems did not modify ESPA. It could be potentiated by an increase in serotoninergic activity following 5-hydroxy-D,L-tryptophan (80-120 mg/kg) and reduced, under certain circumstances, by serotonin depletion with p-chlorophenylalanine (3 x 132 mg/kg). However the serotonin reuptake inhibitors fluoxetine (5 mg/kg) and zimelidine (10 mg/kg) were without effect indicating a complex modulating role of the monoamine. As with morphine-tolerant mice, the induction of ESPA in mice tolerant to methadone and to meperidine has been demonstrated, while the analgesia was not enhanced by chronic naloxone treatment. Although the naloxone reversibility of ESPA has been confirmed, a second acute dose of naloxone (1 mg/kg) did not reverse the analgesia. ESPA could also be fully elicited in adrenalectomized mice. It is concluded that ESPA is a specific type of stimulation-produced analgesia, shorter in duration and pharmacologically more resistant to modulation than others, which might subserve a functional role in response to noxious stimuli.