喹硫平治疗阿尔茨海默病精神行为症状的对照研究

目的 探讨喹硫平治疗阿尔茨海默病精神行为症状的疗效和安全性。方法 选择2015年1月至2017年1月上海市长宁区精神卫生中心收治的伴有精神行为症状的阿尔茨海默病患者63例,将入组患者采用分层区组方法随机分为喹硫平组和美金刚组。喹硫平组32例,给予喹硫平片治疗。美金刚组31例,给予美金刚片治疗。治疗后第1、2、4、8、12、16、20、24周末观察精神行为症状和认知功能的疗效及头晕、困倦等副反应。结果 治疗第24周末,喹硫平组与美金刚组神经精神科问卷总分均下降,不同时间点之间差异有统计学意义（F=194.29,P=0.00）。治疗24周后,两组患者妄想、幻觉、激越、焦虑等因子较基线均有显著下降,差异有统计学意义（P<0.05）。第1周末、第2周末喹硫平组患者精神行为症状的有效率高于美金刚组,差异有统计学意义（P<0.05）。喹硫平组有3例患者发生头晕,困倦2例,乏力1例,血压降低2例。美金刚组有1例患者发生头晕,困倦3例,乏力2例,血压降低1例。两组患者不良反应发生率的差异无统计学意义（P>0.05）。结论 喹硫平与美金刚均能有效缓解阿尔茨海默病患者的精神行为症状,喹硫平比美金刚起效更快。     

脑心通胶囊联合盐酸美金刚治疗血管性痴呆的临床研究

目的探究脑心通胶囊联合盐酸美金刚治疗血管性痴呆患者临床效果。方法选取天津中医药大学第一附属医院2016年4月—2018年1月收治的血管性痴呆患者94例,随机分成对照组和治疗组,每组各47例。对照组口服盐酸美金刚片,第1周剂量5 mg/d,然后每周递增5 mg至第4周达到维持剂量20 mg/d。治疗组在对照组基础上口服脑心通胶囊,3粒/次,3次/d。两组均连续治疗2个月。观察两组患者临床疗效,同时比较治疗前后两组患者认知障碍改善情况、脑血流动力学和血清炎性细胞因子水平。结果治疗后,对照组和治疗组临床总有效率分别为74.47%和91.49%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者日常生活能力量表(ADL)、简易智力状态检查量表(MMSE)和蒙特利尔认知评估量表(MoCA)评分显著升高(P0.05),且治疗组患者ADL、MMSE和MoCA评分明显高于对照组(P0.05)。治疗后,两组大脑前动脉(ACA)、大脑后动脉(PCA)、大脑中动脉(MCA)和左右椎动脉(VA)平均血流速度明显升高(P0.05),且治疗组患者ACA、PCA、MCA、VA平均血流速度明显高于对照组(P0.05)。治疗后,两组患者血清C反应蛋白(CRP)、白细胞介素-18(IL-18)、IL-6、肿瘤坏死因子-α(TNF-α)水平明显降低(P0.05),且治疗组CRP、IL-18、IL-6、TNF-α水平明显低于对照组(P0.05)。结论脑心通胶囊联合盐酸美金刚治疗血管性痴呆患者对认知障碍改善起积极作用,促使脑部血液循环改善,还可抑制炎症反应,具有较高用药安全性,疗效显著。     

石杉碱甲联合美金刚治疗老年性痴呆的临床观察

目的：探讨石杉碱甲联合美金刚治疗老年性痴呆（AD）临床疗效。方法：随机抽取某院门诊及住院老年性痴呆患者42例（年龄69±4.5岁）,分为对照组（20例）,给予石杉碱甲（商品名：哈伯因）及一般常规治疗;试验组（22例）给予石杉碱甲联合美金刚治疗,并给予所有患者简易精神量表（MMSE）、日常生活功能量表（ADL）及神经精神科问卷（NPI）评分,治疗18周后再复查量表评分,用统计学分析方法对终点时两组量表分值作组间对照分析。结果：经组间对照t检验分析结果显示,对照组和试验组MMSE、ADL、NPI有显著性差异（P〈0.05）。结论：石杉碱甲联合美金刚治疗老年性痴呆治疗显效,较单纯应用石杉碱甲对患者的认知功能、日常生活能力及精神行为异常疗效有明显提高。     

Protection of DFP-induced oxidative damage and neurodegeneration by antioxidants and NMDA receptor antagonist

Prophylactic agents acutely administered in response to anticholinesterases intoxication can prevent toxic symptoms, including fasciculations, seizures, convulsions and death. However, anticholinesterases also have long-term unknown pathophysiological effects, making rational prophylaxis/treatment problematic. Increasing evidence suggests that in addition to excessive cholinergic stimulation, organophosphate compounds such as diisopropylphosphorofluoridate (DFP) induce activation of glutamatergic neurons, generation of reactive oxygen (ROS) and nitrogen species (RNS), leading to neurodegeneration. The present study investigated multiple affectors of DFP exposure critical to cerebral oxidative damage and whether antioxidants and NMDA receptor antagonist memantine provide neuroprotection by preventing DFP-induced biochemical and morphometric changes in rat brain. Rats treated acutely with DFP (1.25 mg/kg, s.c.) developed onset of toxicity signs within 7-15 min that progressed to maximal severity of seizures and fasciculations within 60 min. At this time point, DFP caused significant (p < 0.01) increases in biomarkers of ROS (F₂-isoprostanes, F₂-IsoPs; and F₄-neuroprostanes, F₄-NeuroPs), RNS (citrulline), and declines in high-energy phosphates (HEP) in rat cerebrum. At the same time, quantitative morphometric analysis of pyramidal neurons of the hippocampal CA1 region revealed significant (p < 0.01) reductions in dendritic lengths and spine density. When rats were pretreated with the antioxidants N-tert-butyl-α-phenylnitrone (PBN, 200 mg/kg, i.p.), or vitamin E (100 mg/kg, i.p./day for 3 days), or memantine (18 mg/kg, i.p.), significant attenuations in DFP-induced increases in F₂-IsoPs, F₄-NeuroPs, citrulline, and depletion of HEP were noted. Furthermore, attenuation in oxidative damage following antioxidants or memantine pretreatment was accompanied by rescue from dendritic degeneration of pyramidal neurons in the CA1 hippocampal area. These findings closely associated DFP-induced lipid peroxidation with dendritic degeneration of pyramidal neurons in the CA1 hippocampal area and point to possible interventions to limit oxidative injury and dendritic degeneration induced by anticholinesterase neurotoxicity.     

The clinically available NMDA receptor antagonist, memantine, exhibits relative safety in the developing rat brain

The N-methyl-d-aspartate glutamate receptor (NMDAR) has been implicated in preterm brain injury (periventricular leukomalacia (PVL)) and represents a potential therapeutic target. However, the antagonist dizocilpine (MK-801) has been reported to increase constitutive neuronal apoptosis in the developing rat brain, limiting its clinical use in the developing brain. Memantine is another use-dependent NMDAR antagonist with shorter binding kinetics and has been demonstrated to be protective in a rat model of PVL, without effects on normal myelination or cortical growth. To further evaluate the safety of memantine in the developing brain, we demonstrate here that, in contrast to MK-801, memantine at neuroprotective doses does not increase neuronal constitutive apoptosis. In addition, there are no long-term alterations in the expression of NMDAR subunits, AMPAR subunits, and two markers of synaptogenesis, Synapsin-1 and PSD95. Evaluating clinically approved drugs in preclinical neonatal animal models of early brain development is an important prerequisite to considering them for clinical trial in preterm infants and early childhood.     

美金刚联合多奈哌齐对阿尔茨海默病患者认知功能及神经递质的影响

目的 探讨美金刚联合多奈哌齐对阿尔茨海默病(AD)患者认知功能及神经递质的影响.方法 选取北京航天总医院收治的AD患者100例,随机分为试验组(n=50)、对照组(n=50),对照组予以多奈哌齐治疗,试验组在此基础上予以盐酸美金刚治疗,比较2组临床疗效、AD评定量表的认知分量表(ADAS-Cog)评分、神经精神科问卷(...     

美金刚对帕金森病痴呆患者生活质量的影响

目的 评估美金刚对帕金森病痴呆(PDD)患者生活质量的影响。方法 对45例帕金森病痴呆患者采用随机对照试验,评估美金刚治疗6个月后对其生活质量的影响; 通过目标实现缩放(Goal Attainment Scaling, GAS)、帕金森病问卷-8(Parkinson's Disease Questionnaire-8, PDQ-8),Zarit负担量表(Zarit Burden Interview, ZBI)评价患者的生活质量及照料者的负担。结果 治疗6个月后和对照组相比,试验组PDQ-8的改变没有显著差异(P>0.05),但试验组美金刚治疗后平均GAS分数和照顾者负担评分均显著改善(P分别为0.02和0.03)。结论 美金刚可以帮助患者实现更有临床意义的目标并减轻照顾者的负担。     

Failure of memantine to &ldquo;reverse&rdquo; quinpirole-induced hypomotility

AIM: To evaluate antidepressant-like effect of memantine in a rat model. METHODS: Male Wistar rats were treated intraperitoneally with either vehicle, memantine (10 mg/kg) or imipramine (20 mg/kg), for 3 wk. Twenty-four hour after the last treatment animals were challenged with quinpirole (0.3 mg/kg s.c.) and tested for motor activity. After 1 h habituation to the motility cages, the motor response was recorded for the following 45-min and the data were collected in 5-min time bins. RESULTS: As expected, chronic treatment with imipramine potentiated the locomotor stimulant effect of quinpirole. On the contrary, chronic memantine administration failed to induce the behavioral supersensitivity to the dopamine agonist. CONCLUSION: The results show that memantine, at variance with antidepressant treatments, fails to induce dopaminergic behavioral supersensitivity. This observation is consistent with the results of preclinical and clinical studies suggesting that memantine does not have an acute antidepressant action but does have an antimanic and mood-stabilizing effect.     

Anticonvulsant action of 1,3-dimethyl-5-aminoadamantane

Summary The anticonvulsant actions of memantine (1,3-dimethyl-5-aminoadamantane) have been evaluated in mice (seizures induced by maximal electroshock, pentylenetetrazol, bicuculline, picrotoxin, 3-mercaptopropionic acid and N-methyl-d,l-aspartic acid) and in photosensitive baboons, Papio Papio (clonic responses to intermittent photic stimulation). Memantine, 5–20 mg/kg, raised the threshold for electroconvulsions and protected mice against the tonic hind limb extension in pentylenetetrazol-, bicuculline-, picrotoxin-and 3-mercaptopropionic acid-induced seizures, but was ineffective against the clonic phase of chemically-induced seizures. In the baboons, no protection against photomyoclonic responses was observed within 5 h after the intravenous administration of memantine, 1–9 mg/kg. Amantadine, 100 mg/kg, reduced the protective effect of memantine against electroconvulsions. Apomorphine, haloperidol, pimozide, spiroperidol and bicuculline did not modify the anticonvulsant activity of memantine in electroconvulsions. These studies demonstrate an anticonvulsant action of memantine in rodents and suggest that dopaminergic mechanisms do not contribute to its mechanism of action.