Current opinion in investigational drugs最新文献_第7页

Vacc-4x, a therapeutic vaccine comprised of four engineered peptides for the potential treatment of HIV infection. vec -4x是一种治疗性疫苗，由四种工程肽组成，具有治疗HIV感染的潜力。

Current opinion in investigational drugs Pub Date : 2010-08-01

Taff Jones

{"title":"Vacc-4x, a therapeutic vaccine comprised of four engineered peptides for the potential treatment of HIV infection.","authors":"Taff Jones","doi":"","DOIUrl":"","url":null,"abstract":"Vacc-4x is being developed by Bionor Immuno AS as a therapeutic vaccine to be used in conjunction with antiretroviral therapies by individuals infected with HIV. The vaccine is comprised of four synthetic peptides describing sequences from within the highly conserved HIV core protein p24, which are thought to induce T-cell-mediated responses. Vacc-4x was assessed in 51 patients infected with HIV in one phase I and one phase II clinical trial and was demonstrated to be safe and generally well tolerated with no significant adverse events. Promisingly, the vaccine was reported to induce cell-mediated immunity, with a third of vaccinees eligible for follow-up remaining off antiretroviral therapy and being essentially symptom-free 4 years after treatment. Nonetheless, without the inclusion of a placebo group, the data will be looked upon with a degree of skepticism in the scientific community. A phase IIb, placebo-controlled clinical trial to address this issue is currently ongoing, with data expected to become available by the end of 2010. If Vacc-4x vaccinees demonstrate significantly better responses than the placebo group in this trial, the prospects for Vacc-4x could be highly promising.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 8","pages":"964-70"},"PeriodicalIF":0.0,"publicationDate":"2010-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29200700","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: 0

Circadian rhythm dysregulation in bipolar disorder. 双相情感障碍的昼夜节律失调。

Current opinion in investigational drugs Pub Date : 2010-07-01

Ligia Westrich, Jeffrey Sprouse

引用次数: 0

Placebo effects in treating migraine and other headaches. 治疗偏头痛和其他头痛的安慰剂效应。

Current opinion in investigational drugs Pub Date : 2010-07-01

Hans-Christoph Diener

引用次数: 0

Neuroinflammation and the prospects for anti-inflammatory treatment of Parkinson's disease. 神经炎症和帕金森病抗炎治疗的前景。

Current opinion in investigational drugs Pub Date : 2010-07-01

Peter S Whitton

{"title":"Neuroinflammation and the prospects for anti-inflammatory treatment of Parkinson's disease.","authors":"Peter S Whitton","doi":"","DOIUrl":"","url":null,"abstract":"Parkinson's disease (PD) is a progressive neurodegenerative disorder, the cause of which remains elusive. Neuroinflammation appears to be a ubiquitous pathological change in both patients and experimental models of PD, both of which present with the classical features of inflammation, but with evidence that the process has become uncontrolled. Therefore, the use of anti-inflammatory drugs in the treatment of PD appears to be a logical development. Preclinical studies have largely supported the potential of anti-inflammatory compounds in PD. However, reports are conflicting, and preclinical success with these compounds is generally achieved by administration prior to or at the same time as a neurotoxic insult. This regimen, therefore, fails to account for the fact that the disease process is well developed upon diagnosis in patients. Perhaps unsurprisingly, success in the clinic with anti-inflammatory PD compounds has been modest. It has been suggested that anti-inflammatory drugs may be useful as adjuncts to other therapeutic avenues, particularly drugs that aim to restore neuronal loss. Such an approach seems logical given that the etiology of PD is unlikely to arise from a single factor and, accordingly, treatment may require intervention at different mechanistic loci. This review discusses the anti-inflammatory agents that have been suggested to have potential for the treatment of PD.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 7","pages":"788-94"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29075225","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: 0

Cariprazine, an orally active D2/D3 receptor antagonist, for the potential treatment of schizophrenia, bipolar mania and depression. Cariprazine，一种口服D2/D3受体拮抗剂，用于治疗精神分裂症、双相躁狂症和抑郁症。

Current opinion in investigational drugs Pub Date : 2010-07-01

Gerhard Gründer

{"title":"Cariprazine, an orally active D2/D3 receptor antagonist, for the potential treatment of schizophrenia, bipolar mania and depression.","authors":"Gerhard Gründer","doi":"","DOIUrl":"","url":null,"abstract":"Cariprazine (RGH-188), which is being codeveloped by Gedeon Richter Ltd, Forest Laboratories Inc and Mitsubishi Tanabe Pharma Corp, is a novel putative antipsychotic drug that exerts partial agonism at dopamine D2/D3 receptors, with preferential binding to D3 receptors, and partial agonism at serotonin 5-HT1A receptors. Its activity at D2/D3 receptors may be lower than that of the prototype partial agonist aripiprazole. The antipsychotic activity of cariprazine was demonstrated in animal models, and data also suggest that the propensity for extrapyramidal side effects is low and that the drug may have procognitive properties. Cariprazine is rapidly absorbed, with high oral bioavailability and a long plasma elimination t1/2. Cariprazine is in phase III clinical trials in patients with schizophrenia and in patients with bipolar disorder. Data from phase II trials in patients with schizophrenia and bipolar mania indicate that the drug has antipsychotic and antimanic properties that are superior to placebo. With its unique receptor affinity profile, cariprazine may represent a potential enrichment of the therapeutic armamentarium for schizophrenia and affective disorders. Its activity against the cognitive deficits associated with schizophrenia has to be carefully investigated.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 7","pages":"823-32"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29075229","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: 0

Using NMR approaches to drive the search for new CNS therapeutics. 利用核磁共振方法推动寻找新的中枢神经系统疗法。

Current opinion in investigational drugs Pub Date : 2010-07-01

David Borsook, Lino Becerra

{"title":"Using NMR approaches to drive the search for new CNS therapeutics.","authors":"David Borsook, Lino Becerra","doi":"","DOIUrl":"","url":null,"abstract":"The use of MRI-based imaging in drug development has received increased interest recently because of the difficulties associated with the development of CNS pharmacotherapies. While not yet routine, there have been significant advances in imaging that allow this technology to be used for evaluating disease state and drug effects. For disease states, both single and longitudinal studies of non-invasive measures may be obtained to provide a read-out of disease processes and, potentially, to predict the disease state and its evolution. In addition, imaging has enabled the development of improved preclinical disease models based on changes in brain circuitry. Pharmacological MRI, the imaging-based evaluation of drug effects, includes measures of direct effects on the brain, as well as the effects of chronic dosing on brain changes and neurochemical changes associated with these brain effects using magnetic resonance spectroscopy. Thus, imaging may become an integrated process in drug development, during both the preclinical and clinical stages. However, validation, the implementation of good clinical practices and regulatory acceptance are hurdles that remain to be overcome.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 7","pages":"771-8"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010855/pdf/nihms202624.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29077404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The alpha2-delta protein: an auxiliary subunit of voltage-dependent calcium channels as a recognized drug target. α 2- δ蛋白:电压依赖性钙通道的辅助亚基，作为公认的药物靶标。

Current opinion in investigational drugs Pub Date : 2010-07-01

Andrew J Thorpe, James Offord

引用次数: 0

The use of mechanistic biomarkers for evaluating investigational CNS compounds in early drug development. 在早期药物开发中使用机制生物标志物来评估实验性中枢神经系统化合物。

Current opinion in investigational drugs Pub Date : 2010-07-01

Holly D Soares

引用次数: 0

LY-2140023, a prodrug of the group II metabotropic glutamate receptor agonist LY-404039 for the potential treatment of schizophrenia. LY-2140023, II组代谢性谷氨酸受体激动剂LY-404039的前药，用于潜在的精神分裂症治疗。

Current opinion in investigational drugs Pub Date : 2010-07-01

Mario Mezler, Hervé Geneste, Laura Gault, Gerard J Marek

{"title":"LY-2140023, a prodrug of the group II metabotropic glutamate receptor agonist LY-404039 for the potential treatment of schizophrenia.","authors":"Mario Mezler, Hervé Geneste, Laura Gault, Gerard J Marek","doi":"","DOIUrl":"","url":null,"abstract":"LY-2140023 is a methionine amide prodrug of the orthosteric metabotropic glutamate receptor (mGluR)2/3 agonist LY-404039, being developed by Eli Lilly & Co, for the potential oral treatment of schizophrenia. LY-404039 is a rigid glutamate analog that selectively binds to mGluR2/3 compared with all other glutamate receptors and transporters, and with other monoaminergic receptors that have been implicated in the therapeutic efficacy of atypical antipsychotic drugs. Activation of mGluR2 has been associated with the antipsychotic-like behavioral effects of LY-404039, as indicated by experiments using mGluR2-/- and mGluR3-/- mice. Furthermore, mGluR2 acts as a glutamatergic autoreceptor in the brain regions that are believed to be important in the pathophysiology of schizophrenia, such as the prefrontal cortex, striatum, hippocampal formation and the thalamus. The antipsychotic efficacy of LY-2140023, predicted by a common battery of preclinical behavioral screens for antipsychotic drugs, was confirmed in a randomized, placebo-controlled, phase II clinical trial in patients with schizophrenia. In addition, LY-2140023 lacked the extrapyramidal and metabolic side effects that are commonly observed with the majority of currently approved antipsychotic drugs. Thus, LY-2140023 represents a rare psychiatric medicine that demonstrates the promise of being rationally developed from bench to bedside.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 7","pages":"833-45"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29075230","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: 0

Cognitive effects of muscarinic M1 functional agonists in non-human primates and clinical trials. 毒蕈碱M1功能激动剂在非人灵长类动物中的认知作用及临床试验。

Current opinion in investigational drugs Pub Date : 2010-07-01

Robert A McArthur, Julian Gray, Rudy Schreiber

{"title":"Cognitive effects of muscarinic M1 functional agonists in non-human primates and clinical trials.","authors":"Robert A McArthur, Julian Gray, Rudy Schreiber","doi":"","DOIUrl":"","url":null,"abstract":"The limited effect of AChE inhibitors and NMDA receptor antagonists for the treatment of the cognitive symptoms of Alzheimer's disease has prompted the search for new drugs that are capable not only of treating behavioral symptoms, but also of modifying the disease process. Considerable research efforts have been focused on orthosteric muscarinic M1 functional agonists during the past decade to address both these strategies. Part of this research has included the use of non-human primates as models of cognitive impairment to demonstrate preclinical efficacy. No M1 functional agonist has been successfully registered for the treatment of Alzheimer's disease, mostly because of mechanism-related adverse side effects and marginal cognitive effects. However, the M1 agonist xanomeline exhibited preclinical and clinical efficacy for the treatment of the negative and cognitive symptoms of schizophrenia. These results prompted renewed interest in repositioning compounds such as sabcomeline (Proximagen Group plc) for this indication, as well as developing allosteric muscarinic M1 ligands to improve efficacy while reducing side-effect-related attrition. This review discusses preclinical and clinical data from orthosteric M1 functional agonists, focusing on target validation in primate cognition studies, and provides recommendations for testing a new generation of M1 ligands and compounds with novel mechanisms of action.","PeriodicalId":10978,"journal":{"name":"Current opinion in investigational drugs","volume":"11 7","pages":"740-60"},"PeriodicalIF":0.0,"publicationDate":"2010-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29077401","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: 0