CNS drug reviews最新文献_第5页

CNS Axon Regeneration and Nogo 中枢神经系统轴突再生与Nogo

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00176.X

S. Strittmatter

引用次数: 0

Effects of Azaindolizindone Derivatives ZSET845 and ZSET1446 on Acetylcholine Release in the Cortex and Learning Impairments in the Rat Azaindolizindone衍生物ZSET845和ZSET1446对大鼠皮质乙酰胆碱释放和学习障碍的影响

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2004.TB00018.X

Y. Yamaguchi, M. Takano, K. Saitoh, T. Matsuno, S. Kawashima

引用次数: 1

Pitrazepin: Interactions with Transmitter Receptors of the Central and Peripheral Nervous Systems 吡拉西平:与中枢和外周神经系统递质受体的相互作用

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00154.X

A. Demuro, R. Miledi

引用次数: 0

Role of Chaperones in Neurodegeneration 伴侣在神经退行性变中的作用

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00174.X

A. Horwich

引用次数: 0

Olanzapine: Preclinical and Clinical Profiles of a Novel Antipsychotic Agent 奥氮平:一种新型抗精神病药物的临床前和临床研究

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00155.X

G. Tollefson, C. C. Taylor

{"title":"Olanzapine: Preclinical and Clinical Profiles of a Novel Antipsychotic Agent","authors":"G. Tollefson, C. C. Taylor","doi":"10.1111/J.1527-3458.2000.TB00155.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00155.X","url":null,"abstract":"The novel antipsychotic agent olanzapine (Zyprexa, Eli Lilly and Company) is a thienobenzodiazepine analog marketed for the treatment of schizophrenia. Olanzapine's diverse receptor binding profile and greater affinity for serotonin receptors over dopamine receptors is thought to impart antipsychotic efficacy with a low incidence of serious extrapyramidal symptoms (EPS). With once daily dosing steady-state plasma concentrations reached within approximately 1 week. Olanzapine is extensively metabolized by the liver, is mostly excreted in the urine, and has few drug intractions. In clinical trials, the efficacy of olanzapine for treating schizophrenia is better than placebo and haloperidol and comparable to risperidone. Olanzapine may also ameliorate some comorbid symptoms including negative symptoms, depression, anxiety, substance abuse, and cognitive dysfunction, and it is effective in the long-term maintenance of response, treatment-resistance, and improving quality of life. The overall direct costs are lower with olanzapine treatment compared with haloperidol or risperidone treatment. In clinical trials, olanzapine demonstrates a favorable safety profile. The most frequently reported treatment-emergent adverse events are somnolence, schizophrenic reaction, insomnia, headache, agitation, rhinitis, and weight gain. Significantly fewer EPS (based on formal rating scales) and incidences of tardive dyskinesia have been reported for olanzapine compared with haloperidol. Olanzapine has not been associated with persistent elevations of prolactin above the upper limit of normal nor has it been associated with clinically significant changes in cardiac QTc interval. Fewer incidences of suicide attempts have been reported with olanzapine compared with placebo, haloperidol, or risperidone treatments. There is evidence that olanzapine may be effective in the treatment of mood disorders, psychosis associated with Alzheimer's disease, obsessive-compulsive disorder, pervasive developmental disorders, and delirium. Patients with schizophrenia have been successfully switched from other antipsychotics to olanzapine. In conclusion, olanzapine offers a significantly improved risk-to-benefit profile compared with haloperidol and possibly risperidone, and thus should be considered an important treatment option for schizophrenia and related disorders. \u0000 \u0000 \u0000 \u0000SUMMARY \u0000 \u0000Olanzapine is an innovative pharmaceutical product that has been prescribed to more than four million individuals worldwide. Olanzapine has a diverse neurotransmitter receptor binding profile that is similar to clozapine, with selective affinity for the serotonin receptors over the dopamine receptors. In vitro and in vivo preclinical experimentation has provided evidence for the antipsychotic efficacy of olanzapine with a low incidence of serious EPS. In addition, olanzapine has a pharmacokinetic profile that allows for single daily dosing and has minimal metabolic interactions with commonly coadminister","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"73 1","pages":"303-363"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82397187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Highlights from the Sixth International Stockholm/Springfield Meeting on Advances in Alzheimer Therapy Stockholm, Sweden, April 5–8, 2000 2000年4月5日至8日，瑞典斯德哥尔摩，第六届国际阿尔茨海默病治疗进展斯德哥尔摩/春田会议的亮点

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00156.X

E. Giacobini

引用次数: 0

Galanin: neurobiologic mechanisms and therapeutic potential for Alzheimer's disease. 丙氨酸:阿尔茨海默病的神经生物学机制和治疗潜力。

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2001.TB00210.X

S. Counts, S. Perez, Ulrika Kahl, Tamas Bartfai, Robert Bowser, Darlene C. Deecher, Deborah C. Mash, Jacqueline N. Crawley, E. Mufson

{"title":"Galanin: neurobiologic mechanisms and therapeutic potential for Alzheimer's disease.","authors":"S. Counts, S. Perez, Ulrika Kahl, Tamas Bartfai, Robert Bowser, Darlene C. Deecher, Deborah C. Mash, Jacqueline N. Crawley, E. Mufson","doi":"10.1111/J.1527-3458.2001.TB00210.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00210.X","url":null,"abstract":"The neuropeptide galanin (GAL) is widely distributed in the mammalian CNS. Several lines of evidence suggest that GAL may play a critical role in cognitive processes such as memory and attention through an inhibitory modulation of cholinergic basal forebrain activity. Furthermore, GAL fibers hyperinnervate remaining cholinergic basal forebrain neurons in Alzheimer's disease (AD). This suggests that GAL activity impacts cholinergic dysfunction in advanced AD. Pharmacological and in vitro autoradiographic studies indicate the presence of heterogeneous populations of GAL receptor (GALR) sites in the basal forebrain which bind GAL with both high and low affinity. Interestingly, we have recently observed that GALR binding sites increase in the anterior basal forebrain in late-stage AD. Three G protein-coupled GALRs have been identified to date that signal through a diverse array of effector pathways in vitro, including adenylyl cyclase inhibition and phospholipase C activation. The repertoire and distribution of GALR expression in the basal forebrain remains unknown, as does the nature of GAL and GALR plasticity in the AD basal forebrain. Recently, GAL knockout and overexpressing transgenic mice have been generated to facilitate our understanding of GAL activity in basal forebrain function. GAL knockout mice result in fewer cholinergic basal forebrain neurons and memory deficits. On the other hand, mice overexpressing GAL display hyperinnervation of basal forebrain and memory deficits. These data highlight the need to explore further the putative mechanisms by which GAL signaling might be beneficial or deleterious for cholinergic cell survival and activity within basal forebrain. This information will be critical to understanding whether pharmacological manipulation of GALRs would be effective for the amelioration of cognitive deficits in AD.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"57 1","pages":"445-70"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88165953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 41

Donitriptan, a Unique High-Efficacy 5-HT1B/1D Agonist: Key Features and Acute Antimigraine Potential 多尼曲坦，一种独特的高效5-HT1B/1D激动剂:主要特征和急性抗偏头痛潜力

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00153.X

G. John, Michel Perez, P. Pauwels, B. Grand, Y. Verscheure, F. Colpaert

{"title":"Donitriptan, a Unique High-Efficacy 5-HT1B/1D Agonist: Key Features and Acute Antimigraine Potential","authors":"G. John, Michel Perez, P. Pauwels, B. Grand, Y. Verscheure, F. Colpaert","doi":"10.1111/J.1527-3458.2000.TB00153.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00153.X","url":null,"abstract":"We hypothesized that the limited acute therapeutic effectiveness of tryptamine derivatives in alleviating migraine headache could be explained by the relatively low intrinsic activity of these agents at 5-HT1B/1D receptors. Donitriptan is a novel arylpiperazide 5-hydroxytryptamine (5-HT) derivative which was designed to exploit the higher potency and efficacy properties of 5-HT compared to tryptamine at 5-HT1B/1D receptors. \u0000 \u0000 \u0000 \u0000In vitro, donitriptan has subnanomolar affinity for nonhuman and human 5-HT1B/1D receptors and micromolar affinity for the 5-HTip subtype. Donitritpan potently inhibited forskolin-induced cAMP formation and enhanced specific GTP35γS specific binding to a greater extent than tryptamine derivatives and equivalent to 5-HT in C6 cells expressing human 5-HT1B or 5-HT1D receptors. Donitriptan produced more potent and larger amplitude increases in hyperpolarizing Ca2+-dependent K+ current than sumatriptan in guinea pig isolated trigeminal ganglion neurons, and was more potent than tryptamine derivatives in eliciting contractile responses in rabbit isolated saphenous vein rings. \u0000 \u0000 \u0000 \u0000In vivo, donitriptan evoked more potent, longer-lasting and greater amplitude carotid vasoconstrictor responses than tryptamine derivatives in anesthetized pigs; and in contrast to sumatriptan, naratriptan or zolmitriptan, produced long-lasting, dose-dependent decreases in unilateral carotid blood flow in conscious dogs at doses from 0.63 mg/kg p.o. without affecting heart rate or behavior. Oral donitriptan also evoked hypothermic responses in guinea pigs suggesting that the compound gains access to the brain. \u0000 \u0000 \u0000 \u0000Donitriptan is thus a selective, potent 5-HT1B/1D receptor agonist which can be distinguished from tryptamine derivatives in consistently exerting high intrinsic activity at these receptors in a series of vascular and neuronal models relevant to migraine. Advantages in terms of therapeutic effectiveness in the acute relief of migraine headache over currently available triptans can be expected to include greater response rates and consistency of pain relief, a lower incidence of migraine recurrence and better tolerability. The acute anti-migraine potential of the first high efficacy 5-HT1B/1D agonist of its kind, donitriptan, is currently being investigated in man.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"21 1","pages":"278-289"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81650589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Central Nervous System Effects of Celastrol, a Potent Antioxidant and Antiinflammatory Agent 一种有效的抗氧化剂和抗炎剂Celastrol对中枢神经系统的影响

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00137.X

A. Allison, R. Cacabelos, V. Lombardi, X. A. Alvarez, C. Vigo

{"title":"Central Nervous System Effects of Celastrol, a Potent Antioxidant and Antiinflammatory Agent","authors":"A. Allison, R. Cacabelos, V. Lombardi, X. A. Alvarez, C. Vigo","doi":"10.1111/J.1527-3458.2000.TB00137.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00137.X","url":null,"abstract":"Evidence is accumulating that neuronal degeneration in the brains of patients with Alzheimer’s disease (AD) is accompanied by markers of chronic inflammation. These markers include the activation of microglia and the production of the proinflammatory cytokines TNFand IL-1 . Activated microglia release superoxide, which generate reactive oxygen species in the presence of redox-active metals. These, in turn, oxidize lipids to produce 4-hydroxynonenal and other reactive products. Lipid peroxidation adducts as well as other oxidative modifications, including advanced glycation end products and free carbonyls, are observed in the brains of people with AD. In macrophage-lineage cells and in endothelial cells, proinflammatory cytokines induce the expression of an inducible isoform of nitric oxide synthase, which releases relatively high levels of nitric oxide over a long period of time. Nitric oxide and superoxide combine to form peroxynitrite, which damages neurons and other cell types. A marker of peroxynitrite generation is nitrotyrosine, which has been used to demonstrate widespread peroxynitrite-mediated damage in AD brains. If each of the processes described above contributes to the pathogenesis of AD, an effective treatment should: (1) suppress microglial activation; (2) inhibit the production of proinflammatory cytokines; (3) display antioxidant activity; and (4) selectively inhibit the production of NO by the inducible form of NO synthase. The compound should not inhibit constitutive NO synthases in neuronal or endothelial cells, which are required to maintain neuronal function and vascular perfusion. CNS Drug Reviews Vol. 6, No. 1, pp. 45–62 © 2000 Neva Press, Branford, Connecticut This review describes a plant-derived small molecule, celastrol, which in low concentrations displays all the required activities. Furthermore, when administered to rats in low doses, celastrol significantly improves their performance in memory, learning and psychomotor activity tests. The potent antioxidant and antiinflammatory activities of celastrol and its effects on cognitive functions suggest that the drug may be useful to treat neurodegenerative diseases accompanied by inflammation and oxidation, such as AD and Parkinson’s disease.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"151 1","pages":"45-62"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81722110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 11

SNX‐482: A Novel Class E Calcium Channel Antagonist from Tarantula Venom 来自狼蛛毒液的新型E类钙通道拮抗剂SNX‐482

CNS drug reviews Pub Date : 2006-06-07 DOI: 10.1111/J.1527-3458.2000.TB00143.X

R. Newcomb, Xiao-hua Chen, Robin Dean, G. Dayanithi, Cong Ruth, B. Szoke, J. Lemos, S. Bowersox, G. Miljanich

{"title":"SNX‐482: A Novel Class E Calcium Channel Antagonist from Tarantula Venom","authors":"R. Newcomb, Xiao-hua Chen, Robin Dean, G. Dayanithi, Cong Ruth, B. Szoke, J. Lemos, S. Bowersox, G. Miljanich","doi":"10.1111/J.1527-3458.2000.TB00143.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00143.X","url":null,"abstract":"Calcium channels are represented by at least 9 distinct genes (calcium channel classes A-I), corresponding to at least 5 functional and pharmacological “types” (L, N, P/Q, R and T). Selective L-, N-, and T-type channel antagonists are either in clinical use or in late stage clinical trials, while antagonists of P/Q channels are known to be toxic. No selective ligand has been identified for the R-type (class E), and its function and pharmacology are consequently, poorly understood. We review recent work on the discovery and initial characterization of SNX-482, the first known selective antagonist of R-type calcium channels. SNX-482 is a 41 residue acidic peptide with three disulfide bonds that has been isolated from the venom of the African tarantula, Hysterocrates gigas. In cell-based assays, it is a potent and selective inhibitor of the class E or R-type calcium channel. SNX-482 blocks some but not all native R-type currents: it blocks an R-type current in vertebrate neurohypophysis, but it does not block an R-type current in cerebellar granule cells. The peptide blocks oxytocin but not vasopressin release, suggesting a possible utility for SNX-482 as a neuroendocrine modulator. The peptide possesses antiseizure activity in several animal models of epilepsy, suggesting that class E antagonists may have pharmacological use in seizure disorders.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"386 1","pages":"153-173"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77684760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8