石杉碱类似物异香兰石杉碱甲对胆碱酯酶的抑制作用和东莨菪碱导…

研究石杉碱类似物异香兰石杉碱甲（ＩＶＨＡ）对胆碱酯酶的抑制作用和东莨菪碱导致的记忆障碍的影响。方法：乙酰胆碱脂酶和丁酰胆碱酶活力用Ｅｌｌｍａｎ比公法测定。抑九Ｋｉ值和抑制机制用Ｌｉｎｅｗｅａｖｅｒ和Ｂｕｒｋ的双倒数作图测定。行为测试用八臂迷宫装置。结果：ＩＶＨＡ的抗ＡＣｈＥ作用弱于Ｈｕｐ－Ａ。它对红细胞膜ＡＣｈＥ作用稍０．１１μｍｏｌＬ－１。作用强于Ｐｈｙｓ和Ｇａｌ。属混合型制剂，Ｋｉ值为３２ｎｍ     

石杉碱类似物在体外对胆碱酯酶的抑制作用(英文)

用比色法测试表明,14个半合成类似物的抗AChE作用均弱于Hup-A,左旋二氢及四氢类似物的抗BuChE作用稍强于Hup-A,前者属混合型抑制剂,K_i值为0.12μmol·L~(-1)。后者属竞争型抑制剂,K_i值为0.56μmol·L~(-1)。二者不同于异氟磷,与AChE为可逆性结合。     

石杉碱甲改善老年大鼠水迷宫操作记忆障碍(英文)

目的:测试石杉碱甲对自然衰老及东莨菪碱导致的空间记忆缺损的作用。方法:采用大鼠的水迷宫操作,检测石杉碱甲对获得及记忆的作用。结果:连续7天获得试验期间,皮下注射石杉碱甲0.1-0.2mg/kg能明显缩短老年大鼠找到平台的潜伏期。在第8天撤去平台的记忆测试,石杉碱甲0.1,0.2与0.4 mg/kg明显延长老年大鼠在该平台区的游泳时间。单次腹腔注射东莨菪碱0.1mg/kg明显损害已训练达标老年大鼠的空间记忆。皮下注射石杉碱甲0.4 mg/kg明显翻转东莨菪碱产生的记忆损害作用。结论:石杉碱甲能改善老年大鼠自然衰老或东莨菪碱产生的记忆障碍。     

石杉碱甲胶囊提高34对青春期学习记忆和学习成绩

研究石杉碱甲胶囊对初中学生记和学习成绩的效能。方法：采用双盲法,按照心理健康正常,记忆商接近,同班,同性别的要求。将６８例初中学生配对成两组,随机各给石杉碱甲胶囊２粒或空白胶囊２片,一日两次口服,４周为一疗程,以记商及语文英语和数学以及上述三课均分为观测指标评定疗效。结果;石杉碱甲胶囊组疗末的记商明显高于空白组,语文成绩也明显提高。     

石杉碱甲和乙促进小鼠的空间辨别学习和记忆

石杉碱甲和乙是从石杉科石杉属植物蛇足石杉[Huperzia scrrata(Thunb.)Trev.]中分得的二个新生物碱。“Y”迷宫实验表明,ip Hup-A 0.075～0.125 mg/kg或Hup-B 0.4～0.8mg/kg,均能明显促进小鼠的空间辨别学习,并能显著预防CO_2产生的短时识别障碍,促进记忆保持和记忆再现。ig Hup-A 0.1～0.3 mg/kg或Hup-B 0.8 mg/kg也有促进学习的作用。促进作用Hup-A>Phys>Hup-B。剂量与效应曲线呈倒U型。     

石杉碱甲和乙促进小鼠的空间辨别学习和记忆

石杉碱甲和乙是从石杉科石杉属植物蛇足石杉[Huperzia scrrata(Thunb.)Trev.]中分得的二个新生物碱。“Y”迷宫实验表明,ip Hup-A 0.075～0.125 mg/kg或Hup-B 0.4～0.8mg/kg,均能明显促进小鼠的空间辨别学习,并能显著预防CO₂产生的短时识别障碍,促进记忆保持和记忆再现。ig Hup-A 0.1～0.3 mg/kg或Hup-B 0.8 mg/kg也有促进学习的作用。促进作用Hup-A>Phys>Hup-B。剂量与效应曲线呈倒U型。     

石杉碱甲治疗缓解期精神分裂症记忆障碍的临床观察

目的:观察石杉碱甲治疗缓解期精神分裂症记忆障碍的疗效及不良反应。方法:将符合条件的60例缓解期精神分裂症患者随机分为两组,每组30例,分别用石杉碱甲200～400μg/d和安慰剂治疗,疗程12 wk,治疗前后进行临床记忆量表及不良反应量表评定。结果:石杉碱甲对恢复期分裂症记忆障碍的疗效显著优于安慰剂(P<0.05),而不良反应与安慰剂无显著性差异(P>0.05)。结论:石杉碱甲能有效改善缓解期精神分裂症的记忆功能,且不良反应轻微,毒性小。     

石杉碱甲治疗老年性记忆功能减退

石杉碱甲是我国首先从石杉属植物Haperzia serrata(Thunb.)Trev.中分到的一种新生物碱,具有明显抗胆碱酯酶作用。用双盲法,10词提醒测验并与海特琴比较,共观察100例老年性记忆减退患者,其中男54,女46例,年龄46-82岁,石杉碱甲30μg肌注后1-4h记忆功能明显改善,作用持续约6h,无明显副作用,优于海特琴600μg肌注。     

孕酮对东莨菪碱所致记忆损伤小鼠的作用及机制

目的观察孕酮对东莨菪碱所致记忆损伤小鼠的作用及机制。方法东莨菪碱(1mg·kg-1,ip)造成小鼠记忆损伤模型,利用被动逃避实验评价小鼠记忆成绩,并测定给药后24h小鼠皮质和海马胆碱酯酶(AChE)和胆碱乙酰转移酶(ChAT)的活性。结果在被动逃避实验中,东莨菪碱造成小鼠记忆损伤,孕酮(1、10mg·kg-1,sc)预处理能减少跳台错误次数(P<0.05),延长跳台潜伏期(P<0.01)和避暗潜伏期(P<0.01)。东莨菪碱增加皮质和海马AChE活性,降低ChAT活性,孕酮(1mg·kg-1,sc)预处理抑制皮质和海马AChE活性的增加(P<0.01),升高皮质(P<0.05)和海马(P<0.01)ChAT活性。结论孕酮可以改善东莨菪碱所致记忆损伤,机制可能与其抑制皮质和海马AChE活性、升高ChAT活性有关。     

Effects of huperzine A on nucleus basalis magnocellular is lesion-induced spatial working memory deficit

目的：研究石杉碱甲对基底核大细胞部（ＮＢＭ）损毁诱导的工作记忆障碍的影响．方法：采用八臂迷宫延迟插板的程序研究空间记忆．胆碱乙酰转移酶（ＣｈＡＴ）活力测定采用［３Ｈ］乙酰辅酶Ａ转变成［３Ｈ］乙酰胆碱的方法．结果：单侧损毁ＮＢＭ（卡因酸００２μｍｏｌ）导致空间记忆障碍．在不同的延迟间隔，大鼠完成程序产生的正确数减少和错误数增多．损毁侧大脑皮层ＣｈＡＴ酶的含量下降了大约４０％．石杉碱甲（０２ｍｇ·ｋｇ－１实验前３０ｍｉｎｉｐ）改善这种空间记忆障碍．毒扁豆碱（０２－０３ｍｇ·ｋｇ－１实验前２０ｍｉｎｉｐ）也有改善作用．结论：完整的ＮＢＭ是空间记忆形成的关键．石杉碱甲有效的改善ＮＢＭ损毁导致的空间记忆障碍．     

Preventive effect of cholecystokinin octapeptide on scopolamine-induced memory impairment in the rat

In a passive avoidance response, intraperitoneal administration of scopolamine (0.5 mg/kg) at 15 min before the training trials produced a marked impairment of memory in the rat. However, pretreatment with cholecystokinin octapeptide (CCK-8) either given subcutaneously or intracerebroventriculary (i.c.v.) prevented the scopolamine-induced amnesia. Continuous i.c.v. infusion of CCK-8 (1 ng/day) for 7 days significantly prevented the amnesia. The results support our previous findings that CCK-8 has a protective effect against experimental amnesia in the rat.     

石杉碱甲片剂对记忆的作用

老年性痴呆及良性老年性记忆功能减退患者24例,男女各12例,年龄50-68yr,平均58±SD4yr,病程2-10yr,平均5.0±0.4yr。分为治疗组和对照组各12例,应用石杉碱甲片剂100-500μg9组不同剂量tid口服,以双盲法、韦氏记忆量表、十词提醒法对照比较,发现150-300μg的4组的记忆功能有明显提高。     

Effects of 5-HT6 receptor antagonism and cholinesterase inhibition in models of cognitive impairment in the rat

Background and purpose:

The beneficial effect of 5-HT₆ receptor antagonism in cognition remains controversial. This study has been undertaken to reassess the cognition enhancing properties of acute vs subchronic treatment with the selective 5-HT₆ receptor antagonist SB-271046 in unimpaired rats, as well as against scopolamine (cholinergic-) or MK-801 (glutamatergic-mediated) deficits.

Experimental approach:

The Morris water maze was used, measuring behaviour acquisition and retention, and swim speed. Other behavioural measures included yawning and motor activity. SB-271046 was given acutely before each trial or subchronically for 7 days before the trials. The AChE inhibitor galanthamine was also used alone or in combination with SB-271046.

Key results:

Subchronic treatment with SB-271046 improved acquisition in the Morris water maze, while the acute treatment only improved retention. Neither acute nor subchronic SB-271046 treatment reversed scopolamine-induced learning deficits. MK-801 induced learning impairment associated with a behavioural syndrome, reversed by acute, but not subchronic, SB-271046 treatment. Interestingly, combined treatment with galanthamine and SB-271046 reversed the scopolamine- or MK-801-induced learning impairments. Subchronic treatment with SB-271046 did not modify motor activity or the increased number of yawns, a cholinergic-mediated behaviour, induced by single administration of SB-271046.

Conclusions and implications:

These data suggest a potential therapeutic role of 5-HT₆ receptor antagonists such as SB-271046, alone or in combination with galanthamine, in the treatment of cognitive dysfunction, such as those seen in Alzheimer''s disease and schizophrenia.     

Beneficial effects of Urtica dioica on scopolamine-induced memory impairment in rats: protection against acetylcholinesterase activity and neuronal oxidative damage

This study was conducted to investigate protective effects of Urtica dioica extract on acetylcholinesterase (AChE) activity and the oxidative damage of brain tissues in scopolamine-induced memory impairment model. The rats were treated with (1) saline (control), (2) scopolamine, and (3–5) the plant extract (20, 50, or 100?mg/kg) before scopolamine. The traveled distance and the latency to find the platform in Morris water maze (MWM) by scopolamine-treated group were longer while the time spent in target quadrant was shorter than those of the control. Scopolamine decreased the latency to enter the dark in passive avoidance test. Besides, it also increased AChE activity and malondialdehyde (MDA) concentration in the hippocampal and cortical tissues while decreased thiols content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain (p?<?0.01–p?<0.001). Treatment by the extract reversed all the effects of scopolamine (p?<?0.05–p?<0.001). According to the results of present study, the beneficial effects of U. dioica on memory can be attributed to its protective effects on oxidative damage of brain tissue and AChE activity.     

长春西汀改善东莨菪碱诱导的小鼠学习记忆障碍及其机制的研究

目的：研究长春西汀对东莨菪碱诱导小鼠认知损害的影响及其作用机制。方法：采用腹腔注射东莨菪碱（0．8mg·kg^-1·d^-1）制备小鼠认知损害模型,长春西汀连续灌胃给药10d,每天1次,采用Morris水迷宫和避暗实验评价认知功能,并测定脑内乙酰胆碱（Acetylcholine,Ach）、乙酰胆碱酯酶（Acetylch01inesterase,AchE）水平。结果：长春西汀（3、6mg·kg^-1·d^-1）能显著缩短小鼠在隐藏平台实验中寻找平台的潜伏期,增加空间探索实验中平台所在象限停留时间百分率;减少避暗测试中的错误反应次数。长春西汀还能显著增加小鼠脑组织海马区和皮层区Ach含量,并降低AchE活性。结论：长春西汀可通过降低AchE活性,使小鼠脑内Ach含量增加,从而改善东莨菪碱所致的小鼠认知损害。     

TAK—147逆转东莨菪碱诱发的大鼠空间记忆障碍

目的:研究和阐明TAK-147对东莨菪碱诱发的大鼠空间记忆损伤的作用.方法:采用Morris水迷宫的程序研究大鼠的空间记忆,利用开场实验方法测定动物自发活动量.结果:在水迷宫的学习过程中,腹腔内注射东莨菪碱(0.4mg/kg,ip)明显延长大鼠上台的潜伏期,而腹腔内注射TAK-147或donepezil(多奈哌齐)能剂量依赖性地改善东莨菪碱诱发的记忆损伤,两药在0.1-1.0mg/kg的剂量时具有显著性差异.在记忆的再生过程中,腹腔内注射东莨菪碱(1.5mg/kg,ip)引起空间记忆再生过程的障碍分别被TAK-147(0.1,0.3和1.0mg/kg)、多奈哌齐(0.3和1.0mg/kg)以及他克林(3和5mg/kg)显著性改善.TAK-147的作用比多奈哌齐略强却明显强于他克林.此外,在开场实验中,TAK-147和多奈哌齐与生理盐水和东莨菪碱相比,对大鼠运动量未产生明显改变.结论:TAK-147在空间认知功能上起重要的作用,进一步证明TAK-147能够成为一个治疗阿尔采默病的理想的胆碱酯酶抑制药.