双苄基异喹啉季铵类化合物的合成及肌肉松驰活性

目的：获得起效快、复原快的肌肉松驰剂。方法：1类化合物以汉防乙甲素为原料,经季铵化制得。Ⅱ类以阿曲库铵的结构为模板,对其1－取代基进行结构改造而得,所有目的化合物的结构经IR、^1HNMR、MS鉴定。结果：设计合成了未见文献报道的11个两类双苄基异喹啉季铵类化合物。结论：初步药理试验表明,目的化合物1c的起效剂量、起效时间与汉肌松相当。     

1—（9H—卟唑—4—氧）—3—取代氨基—2—丙醇类化合物的合成及生物活性（Ⅰ）

目的：寻找有-β－受体阻滞活性,且高效低毒的化合物。方法：以β－受体阻滞剂咔唑洛尔为先导化合物,根据药物设计中的结构拼合原理,对其内醇胺侧链进行结构修饰,设计并合成了10个1－（9H－卟唑－4－氧）－3－取代氨基－2－丙醇类化合物V1－V10。结果和结论：所合成的目的物均未见文献报道,结构经红外光谱、核磁共振氢谱、质谱、元素分析或高分辨质谱确证。初步药理筛选结果显示,10个化合物均能够不同程度地拮抗异丙肾上腺素引起的心支过速,其中化合物V1、V3、V4的活性与先导化合物相似。     

Preventive effect of magnesium supplement on noise-induced hearing loss in the guinea pig

The effect of magnesium (Mg) on noise-induced hearing loss was investigated in two groups of adult pigmented guinea pigs maintained either on optimal or suboptimal (physiologically high or low) Mg produced by different diets. The total Mg concentrations of the perilymph (PL), cerebrospinal fluid, blood plasma and red blood cells were measured by atomic absorption spectrometry and were found to differ significantly between the two groups (P < 0.01). One ear of each animal was exposed to either a single shooting impulse at a peak pressure level of 187 dB or two impulse noise series at a rate of 1/s and peak pressure levels of 150 dB (1,000 impulses) and 167 dB (2,280 impulses), respectively. Temporary (TTS) and permanent (PTS) hearing threshold shifts in anesthetized animals were measured 2 h and 1 week after the noise exposure, using auditory brain stem response (ABR) audiometry at a frequency range from 3.75 to 30 kHz. Exposure to the single noise impulse resulted in a mean TTS that was significantly lower in the high Mg group than that in the low Mg group (P < 0.05), although no substantial PTS was observed in either group. In the animals exposed to 150 dB noise, the TTS showed a tendency towards an Mg-related reduction at the higher frequencies. A small difference in PTS was found between the low Mg and high Mg groups, but was not significant. Exposure to the 167-dB noise series caused a considerable TTS, which was significantly lower in the high Mg group at 7.5 and 15 kHz than in the low Mg group (P < 0.05). The mean PTS showed a significant difference between the two Mg groups over the whole frequency range (P < 0.05) and was found to correlate negatively with the total Mg concentrations of both PL and plasma (P < 0.05). Moreover, the high Mg group showed a faster recovery from the hearing threshold shift than the low Mg group. The present findings show that preventive oral Mg supplements can significantly reduce the rate of acoustic trauma caused by high-level impulse noise exposure in the guinea pig. Received: 23 March 1999 / Accepted: 15 April 1999     

中药灯盏细辛化学成分的研究(Ⅱ)

目的：进一步研究灯盏细辛「Ｅｒｉｇｅｒｏｎ ｂｒｅｖｉｓｃａｐｕｓ（Ｖａｎｔ．）Ｈａｎｄ．－Ｍａｚｚ．」的化学成分。方法：采用硅胶柱层析对灯盏细辛的氯仿萃取部分的化学成分进行分离和纯化,应用理化常数和光谱分析（ＩＲ,ＭＳ,＾１ＨＮＭＲ,＾１３ＣＮＭＲ）鉴定其结构。结果：得到６个单体化合物,结构分别为３,４－二羟基肉桂酸（３,４－ｄｉｈｙｄｒｏｘｙ－ｐｈｅｎｙｌ ａｃｒｙｌｉｃ ａｃｉｄ,Ⅶ）,α－甲氧基－γ－吡喃酮（α－ｍｅｔｈｏｘｙ－γ－ｐｙｒａｎｏｎｅ,Ⅷ）、豆甾醇（ｓｔｉｇｍａｓｔｅｒｏｌ,Ⅺ）、胡萝卜甙（β－ｓｉｓｔｏｓｔｅｒｏｌ－３－Ｏ－β－Ｄ－ｇｌｕｃｏｐｙｒａｎｏｓｉｄｅ,Ⅻ）。结论：化合物Ⅶ,Ⅷ,Ⅺ,Ⅻ为首次从本植物中分得。     

巯基化合物对毒鼠强急性中毒小鼠的保护作用

目的：探讨巯基化合物对毒鼠强急性中毒小鼠的解毒作用。方法：通过小鼠急性毒性实验,观察多种巯基化合物的解毒作用。结果：巯基化合物能不同程度地延长毒鼠强中毒小鼠的惊厥潜伏期及死亡时间,二巯丙磺纳及二巯丁二纳还可明显降低中毒小鼠死亡率。结论：二巯丙磺纳和二巯丁二钠对毒鼠强中毒小鼠有明显的保护作用,尤以二巯丙磺钠为最佳（Ｐ〈０．００１）。     

胆碱酯酶监测在抢救有机磷农药中毒中的临床意义

目的 探讨胆碱酯酶活性在决定有机磷农药中毒抢救中氯磷定、阿托品的用量,停药时间及对患者预后判断的作用。方法 将口服有机磷农药中毒抢救传统治疗组列为对照组（３２例）,将口服有机磷农药中毒采用胆碱酯酶指导氯磷定、阿托品用量及停药列为观察组（５０例）。结果 观察组阿托品用量和氯磷定用量与对照组阿托品用量和氯磷定用量有显著差异（Ｐ〈０．０１）。观察组治愈５０例,治愈率１００％;对照组治愈２８例,治愈率８７     

The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones

1. The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca²⁺-activated K⁺ (BK_Ca) channel present in neurones isolated from the rat motor cortex.
2. Classical neuroleptic compounds including chlorpromazine and haloperidol applied to the intracellular surface of inside-out patches produced a concentration-dependent reduction in BK_Ca channel activity. Similar effects were observed when these compounds were applied to the extracellular surface of outside-out patches.
3. In contrast, the atypical neuroleptic compounds clozapine and sulpiride did not affect BK_Ca channel activity (100 nM–1 mM) in either inside-out or outside-out patches, while 10 μM pimozide produced 73% of the inhibition produced by 10 μM chlorpromazine.
4. BK_Ca channel activity was also unaffected by application of structurally related tricyclic compounds including the anti-cholinesterase tacrine and the anti-epileptic carbamazepine. The tricyclic antidepressant drug amitriptyline was found to inhibit BK_Ca channel activity but was much less effective than the classical neuroleptic compounds.
5. It is concluded that compounds belonging to the classical neuroleptic group of drugs inhibit BK_Ca channel activity in the rat motor cortex in a structurally-specific manner. This observation may be of clinical significance as it may contribute to some of the side effects associated with classical neuroleptic drug therapy.

     

氧化镁对高血压病人血压,胰岛素抗性及脂质代谢的影响

目的　观察氧化镁对高血压病人血压、胰岛素抗性及脂质代谢的影响。方法　６０例原发性高血压病人随机分为两组,两组病人服用同剂量的钙拮抗剂硝苯地平缓释片降血压,治疗组加服氧化镁粉;对照组不服氧化镁。观察３个月。实验前１ｄ及实验结束之次日分别测血压、抽空腹血查血清葡萄糖（ＳＧ）、血浆胰岛素（ＩＮＳ）、血清胆固醇（ＴＣ）、甘油三酯（ＴＧ）及高密度脂蛋白（ＨＤＬ）,计算胰岛素敏感指数（ＩＳＩ）。观察实验前后各指标的变化。结果　①治疗组实验后收缩压（ＳＢＰ）,舒张压（ＤＢＰ）,ＩＮＳ,ＴＧ及ＴＣ降低,与实验前比较差异有显著性（Ｐ＜０．０５,０．０１）;ＩＳＩ及ＨＤＬ升高,与实验前比较差异有显著性（Ｐ＜０．０１）;ＳＧ治疗前后无显著变化（Ｐ＞０．０５）。②对照组实验后ＳＢＰ,ＤＢＰ降低,与实验前比较差异有显著性（Ｐ＜０．０１）;ＩＮＳ,ＳＧ,ＴＧ,ＴＣ,ＨＤＬ及ＩＳＩ治疗前后无显著差别（Ｐ＞０．０５）。③与对照组比较,治疗组实验后ＳＢＰ及ＤＢＰ降低明显（Ｐ＜０．０５）;ＩＮＳ,ＴＧ,及ＴＣ降低（Ｐ＜０．０１,０．０５）;ＩＳＩ及ＨＤＬ升高（Ｐ＜０．０１）;结论　氧化镁可降低高血压病人的血压、提高其胰岛素敏感性、降低其血清Ｔ     

偶氮胂Ⅲ测定血清镁

目的 :建立简便、灵敏的偶氮胂Ⅲ (ArsenanoⅢ )血清镁测定法。方法 :在碱性条件下 ,用EGTA消除钙的干扰 ,偶氮胂Ⅲ与镁离子形成蓝紫色络合物 ,以分光光度法测定血清镁。结果 :偶氮胂Ⅲ -镁反应液的最大吸收峰为 6 15nm ,反应最适pH8 8,偶氮胂Ⅲ最适浓度为 15 0umol/L ,EGTA加入量为 2 0 0umol/L。本法批内CV及批间CV(n =2 0 )分别为 1 70～ 2 10 %、2 17～ 2 5 7%。平均回收率为 99 3% ,线性 0～ 3 0mmol/L。胆红素 (5 0 0umol/L以内 ) ,血红蛋白 (7g/L)。脂肪乳剂Interlipid(4g/L)对测定无干扰。该法与MTB法对照 ,结果无显著差异。 (P >0 0 5 )。结论 :偶氮胂Ⅲ测定血清镁简便、快速、灵敏、可靠 ,适于手工分析和自动化分析