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Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss 被引量:1
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作者 Qing Wang Xiang Zhang +10 位作者 Yu-Jie Guo Ya-Yan Pang Jun-Jie Li Yan-Li Zhao Jun-Fen Wei Bai-Ting Zhu Jing-Xiang Tang Yang-Yang Jiang Jie Meng Ji-Rong Yue Peng Lei 《Zoological Research》 SCIE CSCD 2023年第4期712-724,共13页
Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delir... Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia.However,given its inherent complexity,few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive.Here,we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors,including anesthesia with surgery(AS),systemic inflammation,and neurotransmission modulation.We found that both bacterial lipopolysaccharide(LPS)and cholinergic receptor antagonist scopolamine(Scop)induction reduced neuronal activities in the delirium-related brain network,with the latter presenting a similar pattern of reduction as found in delirium patients.Consistently,Scop injection resulted in reversible cognitive impairment with hyperactive behavior.No loss of cholinergic neurons was found with treatment,but hippocampal synaptic functions were affected.These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice. 展开更多
关键词 DELIRIUM scopolamine Cholinergic neuron Neuronal activity Brain network
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Kai Xin San ameliorates scopolamine-induced cognitive dysfunction 被引量:12
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作者 Yu-Min Xu Xin-Chen Wang +12 位作者 Ting-Ting Xu Hong-Ying Li Shang-Yan Hei Na-Chuan Luo Hong Wang Wei Zhao Shu-Huan Fang Yun-Bo Chen Li Guan Yong-Qi Fang Shi-Jie Zhang Qi Wang Wei-Xiong Liang 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第5期794-804,共11页
Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this s... Kai Xin San(KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups(which received physiological saline), the doses of KXS(0.7, 1.4 and 2.8 g/kg per day) and donepezil(3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following.(1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze.(2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze.(3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies.(4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus.(5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters. 展开更多
关键词 Kai Xin SAN cognitive DYSFUNCTION scopolamine hydrobromide neuroprotection oxidative stress SYNAPTIC DYSFUNCTION apoptosis CHOLINERGIC system DYSFUNCTION DONEPEZIL neural regeneration
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Neuroprotection of N-benzylcinnamide on scopolamine-induced cholinergic dysfunction in human SH-SY5Y neuroblastoma cells 被引量:1
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作者 Nicha Puangmalai Wipawan Thangnipon +3 位作者 Rungtip Soi-ampornkul Nirut Suwanna Patoomratana Tuchinda Saksit Nobsathian 《Neural Regeneration Research》 SCIE CAS CSCD 2017年第9期1492-1498,共7页
Alzheimer's disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer's disease-like pathology in vivo an... Alzheimer's disease, a progressive neurodegenerative disease, affects learning and memory resulting from cholinergic dysfunction. Scopolamine has been employed to induce Alzheimer's disease-like pathology in vivo and in vitro through alteration of cholinergic system. N-benzylcinnamide (PT-3), purified from Piper submultinerve, has been shown to exhibit neuroprotective properties against amyloid-β-induced neuronal toxicity in rat cortical primary cell culture and to improve spatial learning and memory of aged rats through alleviating oxidative stress. We proposed a hypothesis that PT3 has a neuroprotective effect against scopolamine-induced cholinergic dysfunction. PT-3 (125-200 nM) pretreatment was performed in human neuroblastoma SH-SY5Y cell line following scopolamine induction. PT-3 (125-200 nM) inhibited scopolamine (2 mM)-induced generation of reactive oxygen species, cellular apoptosis, upregutation of ace- tylcholinesterase activity, downregulation of choline acetyltransferase level, and activation of p38 and JNK signalling pathways. These findings revealed the underlying mechanisms of scopolamine-induced Alzheimer's disease-like cellular dysfunctions, which provide evidence for developing drugs for the treatment of this de- bilitating disease. 展开更多
关键词 Alzheimer's disease ACETYLCHOLINE apoptosis acetylcholinesterase inhibitor oxidative stress N-benzylcinnamide natural product scopolamine neuronal regeneration
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Anti-Amnesic Activity of Vitex Negundo in Scopolamine Induced Amnesia in Rats 被引量:1
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作者 Abhinav Kanwal Jogender Mehla +3 位作者 Madhusudana Kuncha Vegi Ganga Modi Naidu Yogendra Kumar Gupta Ramakrishna Sistla 《Pharmacology & Pharmacy》 2010年第1期1-8,共8页
In the present study we investigated the anti-amnesic activity of Vitex negundo in scopolamine induced amnesia in rats. Wistar rats (180-200 g) were trained on active avoidance task. Each animal received session of 15... In the present study we investigated the anti-amnesic activity of Vitex negundo in scopolamine induced amnesia in rats. Wistar rats (180-200 g) were trained on active avoidance task. Each animal received session of 15 trials with inter trial duration of 15 s for 5 days. Scopolamine (3 mg/kg, i.p) was administered at different time periods on the basis of stages of memory i.e acquisition, consolidation and retention in different groups (n = 6). Effect of Vitex negundo extract was evaluated and compared to a standard drug, Donepezil. Significant (p 【0.05) increase in the avoidance response on the 5th session has been observed as compared to 1st session in control group. Scopolamine treatment significantly (p 【0.05) reduced the avoidance response compared to control. Extract treated groups shown significant (p 【0.05) increase in number of avoidance responses as compared to scopolamine treated groups. Increased oxidative stress in brain after scopolamine treatment, as observed by increase in MDA &amp;decrease in GSH &amp;SOD, was lowered in the groups treated with extracts. AChE activity was also improved after V. negundo treatment. Results of the study have shown that V. negundo treated groups decrease the phenomenon of amnesia by increasing learning of memory through antioxidant effect and decreasing AChE activity. 展开更多
关键词 VITEX Negundo AMNESIA Acetylcholinestrase scopolamine Learning and Memory OXIDATIVE Stress
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PROLONGED PARALYSIS OF CHILDREN TREATED WITH SCOPOLAMINE ACUPOINT INJECTION
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作者 Zhang Xiuhui Xiong Cuifeng +3 位作者 Deng Jihua Kong Qingfang Tu Junjie Consultant: Wei Jia, Jiangxi College of TCM, Nanchang, Jiangxi 330006, China 《World Journal of Acupuncture-Moxibustion》 1993年第1期27-30,38,共5页
Authors reported 209 cases of childish paralysis. Of them 104 cases were treatedwith scopolamine acupoint injection, and another 105 cases were divided into 3 groups and treatedwith scopolamine intramuscular injection... Authors reported 209 cases of childish paralysis. Of them 104 cases were treatedwith scopolamine acupoint injection, and another 105 cases were divided into 3 groups and treatedwith scopolamine intramuscular injection, Salviae miltiorrhizae acupoint injection and acupuncture re-spectively as control. The results show that the therapeutic effect of scopolamine acupoint injection ismuch better than that of all other groups. 展开更多
关键词 scopolamine Salviae PARALYSIS ACUPOINT INJECTION
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Nacre extract prevents scopolamine-induced memory deficits in rodents
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作者 Tatsuya Fuji Tatsurou Inoue Yasushi Hasegawa 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2018年第3期202-208,共7页
Objective: To investigate whether the extract from the nacreous layer of pearl oysters(nacre extract) improves impairments in memory caused by scopolamine administration in rodents.Methods: Nacre extract was prepared ... Objective: To investigate whether the extract from the nacreous layer of pearl oysters(nacre extract) improves impairments in memory caused by scopolamine administration in rodents.Methods: Nacre extract was prepared from the inner shell layer of pearl oyster. Effects of nacre extract on scopolamine-induced memory impairment were estimated using novel object recognition test, Y-maze test, and Barnes maze test Effect of nacre extract on mRNA expressions which are genes associated with memory in the hippocampus was investigated using semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) analysis.Results: Administration of nacre extract led to the protection against scopolamine-induced impairments in object recognition, short-term memory, and spatial memory. Treatment with nacre extract reversed the mRNA expression of brain-derived neurotrophic factor(BDNF) and Homer protein homolog 1(Homer-1 a) in the hippocampus, which decreased with the treatment of scopolamine. Conclusions: These results suggest that nacre extract has attenuating effects on memory impairments induced by scopolamine through the increase in mRNA expression of BDNF and Homer-1 a. 展开更多
关键词 Nacre extract scopolamine Memory impairment
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Long-term administration of scopolamine interferes with nerve cell proliferation, differentiation and migration in adult mouse hippocampal dentate gyrus, but it does not induce cell death
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作者 Bing Chun Yan Joon Ha Park +9 位作者 Bai Hui Chen Jeong-Hwi Cho In Hye Kim Ji Hyeon Ahn Jae-Chul Lee In Koo Hwang Jun Hwi Cho Yun Lyul Lee Il-Jun Kang Moo-Ho Won 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第19期1731-1739,共9页
Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the ad... Long-term administration of scopolamine, a muscarinic receptor antagonist, can inhibit the survival of newly generated cells, but its effect on the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus remain poorly understood. In this study, we used immunohistochemistry and western blot methods to weekly detect the biological behaviors of nerve cells in the hippocampal dentate gyrus of adult mice that received intraperito- neal administration of scopolamine for 4 weeks. Expression of neuronal nuclear antigen (NeuN; a neuronal marker) and Fluoro-]ade B (a marker for the localization of neuronal degeneration) was also detected. After scopolamine treatment, mouse hippocampal neurons did not die, and Ki-67 (a marker for proliferating cells)-immunoreactive cells were reduced in number and reac hed the lowest level at 4 weeks. Doublecortin (DCX; a marker for newly generated neurons)-im- munoreactive cells were gradually shortened in length and reduced in number with time. After scopolamine treatment for 4 weeks, nearly all of the 5-bromo-2'-deoxyuridine (BrdU)-labeled newly generated cells were located in the subgranular zone of the dentate gyrus, but they did not migrate into the granule cell layer. Few mature BrdU/NeuN double-labeled cells were seen in the subgranular zone of the dentate gyrus. These findings suggest that long-term administration of scopolamine interferes with the proliferation, differentiation and migration of nerve cells in the adult mouse hippocampal dentate gyrus, but it does not induce cell death. 展开更多
关键词 nerve regeneration NEUROGENESIS scopolamine dentate gyrus cell proliferation neuroblastdifferentiation neuroblast migration granule cell layer neural regeneration
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Anti-Radical and Neuroprotective Potential of <i>Ficus infectoria</i>in Scopolamine Induced Memory Impairment in Mice
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作者 Kiran Zahid Syed Muhammad Faheem Ahmad +1 位作者 Maqsood Ahmed Farah Khan 《Advances in Alzheimer's Disease》 2018年第2期62-77,共16页
Ficus infectoria has a wide distribution in Bangladesh, Nepal, Pakistan, Sri Lanka, Southwest China and Indochina and is an enrich source of phytochemicals thereby possess antibacterial, antifungal and hyperglycaemic ... Ficus infectoria has a wide distribution in Bangladesh, Nepal, Pakistan, Sri Lanka, Southwest China and Indochina and is an enrich source of phytochemicals thereby possess antibacterial, antifungal and hyperglycaemic activities. In this study, we attempted to examine the cognitive ability of methanolic and ethanolic extract of F. infectoria fruit extract in scopolamine induced memory impairment in mice by using preliminary phytochemical and antioxidant tests, and the cognitive ability of the methanolic and ethanolic fruit extract of F. infectoria. Fruit extract was analyzed in scopolamine amnesia mice using passive avoidance approach. Piracetam was used as a reference drug (200 mg/Kg). Further confirmation was provided by means of mice brain homogenate biochemical tests. Maximum phytochemical, antioxidant activity and nootropic ability were observed in the ethanolic fruit extract of F. infectoria. Plant extract was used at three doses i.e. 75 mg/Kg, 150 mg/Kg and 300 mg/Kg and exhibited nootropic abilities in all tests used. Enhanced SDL value i.e. (291.2 ± 0.33+++###) was observed by the administration of plant extract at all dose range in comparison to reference drug i.e. piracetam (252.8 ± 1.60###) used in the study. The plant extract utilization has showed increase in total protein (25.08 ± 0.26+++### mg/g of tissue) and reduced glutathione content (33.0 ± 0.46+++### nmoles/mg of protein) and vice versa while low malondialehyde (MDA) (9.18 ± 0.17+++### nmoles/mg of protein) and AChE activity (0.067 ± 0.009+++### M/min/g protein). However, opposite situation was observed in the scopolamine amnesia mice. Hence it was concluded the plant extract possessed neuroprotective activity in the scopolamine induced cognitive decline in mice thereby used as cost effective natural medicines in near future. 展开更多
关键词 Antioxidant Malondialdehyde Reduced Glutathione Acetylcholinestrase scopolamine Hydrobromide NEUROPROTECTIVE FICUS infectoria
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Liquid Chromatographic Determination of Scopolamine in Hair with Suspended Drop Liquid Phase Microextraction Technique
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作者 Mahboubeh Masrournia Zarrin Es’ haghi Mostafa Amini 《American Journal of Analytical Chemistry》 2011年第2期235-242,共8页
Hair analysis is used in some branches of alternative medicine as a method of investigation to assist diagnosis. It is very useful when a history of drug use is difficult or impossible to obtain. In this re-search sus... Hair analysis is used in some branches of alternative medicine as a method of investigation to assist diagnosis. It is very useful when a history of drug use is difficult or impossible to obtain. In this re-search suspended droplet liquid phase microextraction (SDLME) coupled with high-performance liquid chromatography and photodiode array detection (HPLC-DAD) was used for preconcentration and analysis of scopolamine in hair samples. Therefore scopolamine was extracted from 2.0 g hair sample incubated in methanol (5 h, 50°C) and adjusted to pH 7.4 with, Na2HPO4–H3PO4 buffer solution (donor phase, P1) into an organic phase (P2) 350 μl n-octanol and then back extracted into a micro drop of aqueous acceptor phase (P3), adjusted at pH 3, with HCL. The extraction time, T1 (from P1 to P2) was 2 min and T2 (from P2 to P3) was 30 min. Optimum instrumental conditions were included;A C18 reverse phase column with water-acetonitrile-methanol (80:10:10) as the mobile phase was used and wavelength for UV detec-tion was 205 nm. The linear range was 10 to 10000 ng●mL–1, enrichment factor, detec-tion limit and relative standard deviation were 77, 0.1 ng●mL–1 and 5.4 respectively. 展开更多
关键词 Column LIQUID CHROMATOGRAPHY Directly Suspended DROPLET LIQUID Phase MICROEXTRACTION (SDLME) scopolamine HAIR Sample
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Effects of Scopolamine on Blood Vessels in Rabbit Ear after Sympathetic and Sensory Denervation
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作者 刘书勤 臧伟进 +3 位作者 成亮 李增利 于晓江 李宝平 《South China Journal of Cardiology》 CAS 2004年第1期38-43,共6页
Objectives To investigatethe effects and involved mechanisms of scopolamine(Scop) on rabbit ear blood vessels. Methods Rabbitear blood vessels were desympathetic and desensoryinnervation with surgical operation. Diame... Objectives To investigatethe effects and involved mechanisms of scopolamine(Scop) on rabbit ear blood vessels. Methods Rabbitear blood vessels were desympathetic and desensoryinnervation with surgical operation. Diameters of dor-sal auricular arterial trunks in vivo were measuredwith a pair of compasses and the ruler in a dissectingmicroscope, and effluents from isolated ear underconstant perfusion pressure were recorded with a digi-tal drop-recorder. Results Intramuscular injectionof Scop 0.1 mg/kg made the diameter of denerveddorsal auricular arterial trunks, as well as that of in-nerved ones, significantly increased. Scop by itself,atthe maximal concentration (Cmax) of 3μM, 30μMand 300μM, did not alter the effluent flow from theisolated denervated rabbit ear, but chlorpromazine(CPZ), at Cmax of 1μM, acetylcholine (ACh), 0.25μM, all significantly increased the effluent flow, andnorepinephrine (NE), 0.1μM, significantly decreasedthe effluent. Scop, 3μM, did not affect ACh (0.25μM)-induced the increase of effluent flow, but Scop,30μM, alleviated the increase. Scop, 3μM, did notaffect NE (0.1μM)-induced the decrease of effluentflow, but Scop, 10, 30 and 100μM, significantly alle-viated the decrease. Conclusions The study sug-gests that Scop has no direct vasodilator effect. Thevasodilator effect of Scop is not due to the blockade ofmuscarinic receptor. However, Scop can dilate bloodvessels contracted by α_1-adrenoceptor activation. 展开更多
关键词 scopolamine VASODILATATION Rabbit ear DENERVATION
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Novel insights on acetylcholinesterase inhibition by Convolvulus pluricaulis,scopolamine and their combination in zebrafish
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作者 Kalyani Bindu Karunakaran Anand Thiyagaraj Kirankumar Santhakumar 《Natural Products and Bioprospecting》 2022年第1期56-70,共15页
Acetylcholinesterase(AChE)inhibitors increase the retention of acetylcholine(ACh)in synapses.Although they allevi-ate cognitive deficits in Alzheimer’s disease,their limited benefits warrant investigations of plant e... Acetylcholinesterase(AChE)inhibitors increase the retention of acetylcholine(ACh)in synapses.Although they allevi-ate cognitive deficits in Alzheimer’s disease,their limited benefits warrant investigations of plant extracts with similar properties.We studied the anti-AChE activity of Convolvulus pluricaulis(CP)in a zebrafish model of cognitive impair-ment induced by scopolamine(SCOP).CP is a perennial herb with anti-amnesiac and anxiolytic properties.It contains alkaloid,anthocyanin,coumarin,flavonoid,phytosterol and triterpenoid components.Isoxazole(ISOX)was used as a positive control for AChE inhibition.CP-treated 168 hpf larvae showed a similar pattern of AChE inhibition(in the myelencephalon and somites)as that of ISOX-treated larvae.CP was superior to ISOX as evidenced by the retention of avoidance response behavior in adult zebrafish.Molecular docking studies indicated that ISOX binds Ser203 of the catalytic triad on the human AChE.The active components of CP-scopoletin and kaempferol-were bound by His447 of the catalytic triad,the anionic subsite of the catalytic center,and the peripheral anionic site.This suggested the ability of CP to mediate both competitive and non-competitive modes of inhibition.Surprisingly,SCOP showed AChE inhibition in larvae,possibly mediated via the choline-binding sites.CP+SCOP induced a concentration-dependent increase in AChE inhibition and ACh depletion.Abnormal motor responses were observed with ISOX,CP,ISOX+SCOP,and CP+SCOP,indicative of undesirable effects on the peripheral cholinergic system.Our study proposes the examination of CP,SCOP,and CP+SCOP as potential AChE inhibitors for their ability to modulate cognitive deficits. 展开更多
关键词 Alzheimer’s disease ACETYLCHOLINESTERASE ZEBRAFISH Convolvulus pluricaulis scopolamine ISOXAZOLE
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SYNTHESIS OF A NEW TYPE OF SCOPOLAMINE ANALOGUES
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作者 Guo Hua CHU Qi Ting ZHOU Dong Lu BAI Ru Yun JI Shanghai Institute of Materia Medica,Chinese Academy of Sciences.Shanghai 200031 《Chinese Chemical Letters》 SCIE CAS CSCD 1993年第6期485-488,共4页
A series of compounds,which are structurally analogous to scopolamine and also in accordance with the general formula of neuroleptic benzamides,were synthesized and tested for their potential antipsychotic activity.
关键词 SYNTHESIS OF A NEW TYPE OF scopolamine ANALOGUES THP DBU PPM
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Clinical Assessment of the Use of Propinox Hydrochloride and Scopolamine Hydrochloride in the Treatment of Abdominal Colic: A Retrospective, Comparative Study
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作者 Helio Rzetelna Carlos Frederico Porto Alegre Rosa +6 位作者 Mario Kirzner Lucas Pereira Jorge de Medeiros Camila Melo Marcia Gonçalves Ribeiro Lisa Oliveira José Galvão Alves Mauro Geller 《International Journal of Clinical Medicine》 2016年第7期474-480,共8页
Objectives: The purpose of this study was to evaluate and compare the use of propinox hydrochloride and scopolamine hydrochloride in patients presenting abdominal colic (abdominal pain), in terms of treatment efficacy... Objectives: The purpose of this study was to evaluate and compare the use of propinox hydrochloride and scopolamine hydrochloride in patients presenting abdominal colic (abdominal pain), in terms of treatment efficacy and tolerability. Material & Methods: This was an analytical, retrospective, comparative study based on hospital records of outpatients treated at Servi&ccedilo de Clínica Médica do Hospital das Clínicas Costantino Otaviano (HCTCO) and at Santa Casa de Misericórdia do Rio de Janeiro, from 1988-1998. Subjects were divided into two groups: patients from Group 1 were treated with propinox hydrochloride, while patients from Group 2 were treated with scopolamine hydrochloride. Statistical analysis was performed using GraphPad Prism version 5.0. For comparison of categorical variables, we used the chi-squared or Fisher’s test, while continuous variables were analyzed using ANOVA or the Student’s T test. Results: A total of 1042 subjects were included, of which 525 were allocated to Group 1 and 517 to Group 2. Mean treatment duration was 9.166 days (±4.208) in Group 1 and 8.795 days (±5.052) in Group 2, with no statistically significant difference in treatment duration between the two groups (p = 0.198). All subjects in Group 1 were treated with propinox 10 mg (2 coated tablets, three times per day) while all subjects in Group 2 were treated with scopolamine hydrochloride 10 mg (2 coated tablets, three times per day). There were no statistically significant between-group differences in weight, BMI, heart rate, and respiratory rate at pre- and post-treatment;with the exception of higher post-treatment systolic blood pressure in Group 1, blood pressure measures also remained homogenous. Adverse events were reported among both treatment groups with no significant between-group difference in incidence (p = 0566). At pretreatment, pain intensity was more severe in Group 1 (p = 0.0257), while at post-treatment, there was no statistically significant difference between the two treatment groups (p = 0.895). There was a statistically significant improvement in pain intensity within both treatment groups (χ<sup>2</sup> = 631.4;df = 3;p < 0.0001 for Group 1 and χ<sup>2</sup> = 554.3;df = 3;p < 0.0001 for Group 2). Conclusion: The results obtained in this study indicate a therapeutic equivalence between propinox hydrochloride and scopolamine hydrochloride. Both treatments demonstrated good efficacy and tolerability in the treatment of abdominal colic pain, in the population evaluated. 展开更多
关键词 Abdominal Colic Propinox Hydrochloride scopolamine Hydrochloride
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Systems pharmacology modeling in neuroscience: Prediction and outcome of PF-04995274, a 5-HT4 partial agonist, in a clinical scopolamine impairment trial
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作者 Timothy Nicholas Sridhar Duvvuri +8 位作者 Claire Leurent David Raunig Tracey Rapp Phil Iredale Carolyn Rowinski Robert Carr Patrick Roberts Athan Spiros Hugo Geerts 《Advances in Alzheimer's Disease》 2013年第3期83-98,共16页
Background: 5-HT4receptors in cortex and hippocampus area are considered as a possible target for modulation of cognitive functions in Alzheimer’s disease (AD). A systems pharmacology approach was adopted to evaluate... Background: 5-HT4receptors in cortex and hippocampus area are considered as a possible target for modulation of cognitive functions in Alzheimer’s disease (AD). A systems pharmacology approach was adopted to evaluate the potential of the 5-HT4 modulation in providing beneficialeffects on cognition in AD. Methods: A serotonergic synaptic cleft model was developed by integrating serotonin firing, release, synaptic half-life, drug/tracer properties (affinity and agonism) as inputs and5-HT4 activity as output. The serotonergic model was calibrated using bothinvivo data on free 5-HT levels in preclinical models and human imaging data. The model was further expanded to other neurontransmitter systems and incorporated into a computer-based cortical network model which implemented the physiology of 12 different membrane CNS targets. A biophysically realistic, multi-compartment model of 80 pyramidal cells and 40 interneurons was further calibrated usingdata reported for working memory tasks in healthyhumans and schizophrenia patients. Model output was the duration of the network firing activity in response to an external stimulus. Alzheimer’s disease (AD) pathology, in particular synapse and neuronal cell loss in addition to cholinergic deficits, was calibrated to align with the natural clinical disease progression. The model was used to provide insights into the effect of 5-HT4 activation on working memory and to prospectively simulate the response of PF- 04995274, a 5-HT4partial agonist, in a scopolamine-reversal trial in healthy human subjects. Results: The model output suggested a beneficial effect of 5-HT4 agonism on working memory. The model also projected no effect or an exacerbation of scopolamine impairment for low in- trinsic activity 5-HT4agonists, which was supported by the subsequent human trial outcome. The clinical prediction of the disease model strongly suggests that 5-HT4 agonists with high intrinsic activity may have a beneficial effect on cognition in AD patients. 展开更多
关键词 SYSTEMS PHARMACOLOGY 5-HT4 Receptor Partial AGONIST scopolamine-Reversal
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原生二十二碳六烯酸纯牛奶对小鼠学习记忆功能的辅助改善作用
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作者 任吴疆 郭月逸 +3 位作者 赵建 郭豫 霍清 刘彦霞 《中国乳品工业》 CAS 北大核心 2024年第1期11-16,共6页
探讨了原生二十二碳六烯酸纯牛奶对小鼠学习记忆障碍的辅助改善作用。将SPF级昆明小鼠设置为正常小鼠、记忆获得障碍模型小鼠两个模型,每个模型中包含对照组,低(6.67 mg/kg体质量)、中(13.33 mg/kg体质量)、高(40.00 mg/kg体质量)剂量... 探讨了原生二十二碳六烯酸纯牛奶对小鼠学习记忆障碍的辅助改善作用。将SPF级昆明小鼠设置为正常小鼠、记忆获得障碍模型小鼠两个模型,每个模型中包含对照组,低(6.67 mg/kg体质量)、中(13.33 mg/kg体质量)、高(40.00 mg/kg体质量)剂量组。各组小鼠灌胃30 d的受试物后,依次进行跳台、避暗和水迷宫实验检测小鼠的学习记忆能力。跳台实验结果显示,与模型对照组相比,模型中、高剂量组测试期潜伏期显著延长(P<0.05)并且错误次数极显著减少(P<0.01);避暗实验结果显示,与阴性对照组相比,中剂量组消退期错误次数和错误动物数均显著减少(P<0.05);水迷宫实验结果显示,与模型对照组相比,模型中剂量组到达终点的总时间显著减少(P<0.05)。结论为原生二十二碳六烯酸纯牛奶可以通过延长测试潜伏期并减少错误次数和错误动物数起到辅助改善小鼠学习和记忆障碍的作用。 展开更多
关键词 二十二碳六烯酸 学习记忆 东莨菪碱 多不饱和脂肪酸
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肾穿刺微造瘘联合丁溴东莨菪碱在软镜碎石术中对肾结石的治疗有效性及安全性研究
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作者 杜风 《黑龙江医学》 2024年第14期1704-1706,共3页
目的:探析经皮肾穿刺微造瘘取石术(MPCNL)联合丁溴东莨菪碱在输尿管软镜碎石术(FURL)中对肾结石的治疗有效性及安全性。方法:选取2021年7月—2022年11月河南科技大学第一附属医院开元手术部收治的80例肾结石患者作为研究对象,采用随机... 目的:探析经皮肾穿刺微造瘘取石术(MPCNL)联合丁溴东莨菪碱在输尿管软镜碎石术(FURL)中对肾结石的治疗有效性及安全性。方法:选取2021年7月—2022年11月河南科技大学第一附属医院开元手术部收治的80例肾结石患者作为研究对象,采用随机数表法将其分为对照组和观察组,每组各40例。对照组给予FURL联合丁溴东莨菪碱,观察组在对照组基础上联合MPCNL治疗。对比两组患者临床有效率、疗效及康复指标、术前术后肾损伤相关因子[丛生蛋白(CLU)、肾损伤分子-1(KIM-1)、血清肌酐(SCr)]、并发症风险情况。结果:观察组患者临床有效率(97.50%)明显高于对照组(80.00%),差异有统计学意义(χ^(2)=6.135,P<0.05);观察组患者手术时间长于对照组,住院、结石清除及肾绞痛缓解时间均短于对照组,差异有统计学意义(t=15.090、5.755、8.596、6.043,P<0.05);术后两组患者CLU、KIM-1、SCr水平明显升高,且观察组上升幅度低于对照组,差异有统计学意义(t=2.761、6.704、3.079,P<0.05);观察组患者并发症发生率(5.00%)明显低于对照组(20.00%),差异有统计学意义(χ^(2)=4.114,P<0.05)。结论:MPCNL联合丁溴东莨菪碱应用于肾结石FURL治疗中效果显著,可提高结石清除有效率及安全性,缩短康复时间,降低肾损伤风险。 展开更多
关键词 肾结石 输尿管软镜碎石术 肾穿刺微造瘘取石术 丁溴东莨菪碱 疗效 安全性
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基于斑马鱼模型评价磷脂酰丝氨酸对记忆力及认知力的改善作用
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作者 夏洪志 《中国食品添加剂》 CAS 2024年第2期145-152,共8页
利用斑马鱼模型评价磷脂酰丝氨酸(PS)对东莨菪碱所致的记忆力及认知力损伤是否有改善作用。采用成年斑马鱼做为试验模型,设置空白对照组、东莨菪碱模型组、多奈哌齐阳性药组及三个浓度(1、3、9 mg/L)的PS共处理组,药物干预培养6天,第7天... 利用斑马鱼模型评价磷脂酰丝氨酸(PS)对东莨菪碱所致的记忆力及认知力损伤是否有改善作用。采用成年斑马鱼做为试验模型,设置空白对照组、东莨菪碱模型组、多奈哌齐阳性药组及三个浓度(1、3、9 mg/L)的PS共处理组,药物干预培养6天,第7天时,记录斑马鱼行为学变化,检测学习记忆相关基因与抗氧化相关基因的表达变化,并做统计学分析。结果表明,与对照组相比,东莨菪碱模型组斑马鱼主要表现出记忆力下降和认知力丧失的行为现象,且各基因表达出现异常。与东莨菪碱模型组比较,阳性药组与三个浓度的PS共处理组的斑马鱼记忆力和认知力得到一定恢复,且各基因表达趋于正常。因此,浓度为1、3和9 mg/L的PS对东莨菪碱所致斑马鱼记忆力和认知力的损伤具有一定的改善作用。 展开更多
关键词 磷脂酰丝氨酸 东莨菪碱 斑马鱼
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红花黄色素对SCOP诱导小鼠认知功能损伤的保护作用
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作者 齐妍强 叶红霞 +5 位作者 王妍又 李霞 贺颖西 田卉 李乐 胡艳丽 《中国药理学通报》 CAS CSCD 北大核心 2024年第10期1858-1865,共8页
目的 研究红花黄色素(safflower yellow, SY)对氢溴酸东莨菪碱(scopolamine hydrobromide, SCOP)诱导的记忆障碍模型小鼠学习记忆的作用。方法 6月龄C57BL/6J小鼠随机分为Control组、Model组、SY-H组、SY-M组、SY-L组、石杉碱甲(huperzi... 目的 研究红花黄色素(safflower yellow, SY)对氢溴酸东莨菪碱(scopolamine hydrobromide, SCOP)诱导的记忆障碍模型小鼠学习记忆的作用。方法 6月龄C57BL/6J小鼠随机分为Control组、Model组、SY-H组、SY-M组、SY-L组、石杉碱甲(huperzine-A)组,每组12只。采用SCOP建立记忆障碍模型,通过行为学实验评价记忆障碍模型小鼠的空间学习记忆和认知能力,ELISA试剂盒测定小鼠皮层胆碱能神经系统功能,尼氏染色观察脑组织病理变化情况,Western blot检测各组小鼠脑组织突触可塑性及BDNF/TrkB/CREB通路相关蛋白表达。结果 与Model组相比,各给药组小鼠学习记忆能力提高;海马和皮层神经元排列整齐,细胞形态趋于完整,正常神经元数量升高;皮层胆碱能神经系统功能显著改善,突触可塑性相关蛋白表达量升高,脑组织BDNF/TrkB/CREB信号通路激活。结论 SY能显著改善SCOP诱导的认知障碍小鼠的学习记忆能力,其作用机制可能是通过改善胆碱能神经系统功能,激活BDNF/TrkB/CREB信号通路,调节突触可塑性,改善神经元损伤,进而发挥神经保护作用。 展开更多
关键词 阿尔茨海默病 红花黄色素 氢溴酸东莨菪碱 胆碱能神经系统 BDNF/TrkB/CREB通路 突触可塑性
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坦索罗辛联合丁溴东莨菪碱治疗体外冲击波碎石术后单发肾结石的临床效果观察
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作者 林精精 《中国现代药物应用》 2024年第4期89-92,共4页
目的观察丁溴东莨菪碱联合坦索罗辛治疗体外冲击波碎石术后单发肾结石的临床效果。方法选取70例单发肾结石患者纳入本研究,以随机数字表法分成对照组与试验组,每组35例。两组患者均接受体外冲击波碎石术治疗,对照组术后给予丁溴东莨菪... 目的观察丁溴东莨菪碱联合坦索罗辛治疗体外冲击波碎石术后单发肾结石的临床效果。方法选取70例单发肾结石患者纳入本研究,以随机数字表法分成对照组与试验组,每组35例。两组患者均接受体外冲击波碎石术治疗,对照组术后给予丁溴东莨菪碱促进结石排出,试验组术后给予丁溴东莨菪碱+坦索罗辛促进结石排出。治疗后,对比两组患者治疗效果、结石排出时间、肾绞痛消失时间、炎症指标改善情况以及治疗安全性。结果治疗后,试验组治疗总有效率100.00%高于对照组的80.00%(P<0.05);试验组结石排出时间、肾绞痛消失时间分别为(8.31±9.76)、(7.08±0.47)d,短于对照组的(13.66±2.33)、(10.55±0.78)d(P<0.05);试验组肿瘤坏死因子-α(TNF-α)(43.25±3.15)ng/L、白细胞介素-6(IL-6)(23.84±2.32)ng/L、C反应蛋白(CRP)(39.88±3.19)mg/L均低于对照组的(53.36±3.76)ng/L、(29.77±2.77)ng/L、(48.92±3.44)mg/L(P<0.05);两组治疗期间不良反应发生率对比,差异无统计学意义(P>0.05)。结论对接受体外冲击波碎石术治疗的单发肾结石患者术后应用丁溴东莨菪碱联合坦索罗辛治疗具有显著临床效果,可有效缩短结石排出时间、肾绞痛消失时间,炎性程度得到抑制,且并未增加用药不良反应发生风险,临床应用价值显著。 展开更多
关键词 单发肾结石 坦索罗辛 体外冲击波碎石术 丁溴东莨菪碱 临床疗效
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黄毛耳草中东莨菪内酯的HPLC含量测定及提取工艺优化研究
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作者 金贤武 周燕霞 《宜春学院学报》 2024年第6期17-20,125,共5页
目的:建立黄毛耳草中东莨菪内酯的HPLC含量测定方法,并优化其提取工艺。方法:色谱柱waters symmetry C_(18)(4.6 mm×250 mm,5μm),流动相乙腈0.1%磷酸水,检测波长345 nm,流速0.8 mL/min,进样量10μL,测定东莨菪内酯含量。采用超声... 目的:建立黄毛耳草中东莨菪内酯的HPLC含量测定方法,并优化其提取工艺。方法:色谱柱waters symmetry C_(18)(4.6 mm×250 mm,5μm),流动相乙腈0.1%磷酸水,检测波长345 nm,流速0.8 mL/min,进样量10μL,测定东莨菪内酯含量。采用超声提取法,以乙醇浓度、超声时间、超声功率和料液比为考察因素,以东莨菪内酯含量为评价指标,优化其提取工艺。结果:最佳提取工艺为乙醇浓度74%、提取时间45 min、超声功率250 W、液料比25∶1。精密称取3份黄毛耳草样品,每份2.0 g,此条件下东莨菪内酯的提取含量为为81.97μg/g,与预测值81.41μg/g无显著性差异。结论:本试验建立的HPLC法可用于黄毛耳草中东莨菪内酯的含量测定,所优化的提取工艺稳定可靠、简便可行。 展开更多
关键词 HPLC Box Behnken响应面 黄毛耳草 东莨菪内酯 工艺优化
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