CNS drug reviews最新文献

{"title":"Nefazodone: A Review of Its Neurochemical Mechanisms, Pharmacokinetics, and Therapeutic Use in Major Depressive Disorder","authors":"Handan He,&nbsp;J. Steven Richardson","doi":"10.1111/j.1527-3458.1997.tb00315.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00315.x","url":null,"abstract":"<div>\u0000 \u0000 <p>Nefazodone, an antidepressant agent with a phenylpiperazine structure, has a pharmacological profile that is distinct from other antidepressant drugs. Like many other antidepressants, nefazodone inhibits the reuptake of norepinephrine and serotonin from the synaptic cleft. Unlike other antidepressants, nefazodone is also a potent antagonist of 5-HT₂ serotonergic receptors. In addition, nefazodone is a weak antagonist of α₁-adrenergic receptors, but has little or no affinity for cholinergic, histaminergic, or dopaminergic receptors. In placebo-controlled clinical trials, nefazodone has been found to be an effective antidepressant drug with minimal cardiovascular action and significantly fewer side effects than imipramine. Since nefazodone is an effective antidepressant with a low incidence of serious adverse effects, it may be particularly useful in major depressive disorder patients who are intolerant of the anticholinergic or serotonergic side effects of other antidepressants, or who do not respond to treatment with other antidepressant agents. In this paper, we review the mechanisms of action, the pharmacokinetics, and the antidepressant efficacy of nefazodone.</p>\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 1","pages":"34-48"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00315.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81630820","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}

{"title":"Linopirdine: Pharmacology of a Neurotransmitter Release Enhancer","authors":"Robert Zaczek,&nbsp;Robert J. Chorvat,&nbsp;Barry S. Brown","doi":"10.1111/j.1527-3458.1997.tb00319.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00319.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 2","pages":"103-119"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00319.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89329593","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}

{"title":"Propentofylline (HWA 285), a Neuroprotective Glial Cell Modulator: Pharmacologic Profile","authors":"K. Rudolphi,&nbsp;C. K. Park,&nbsp;M. Rother","doi":"10.1111/j.1527-3458.1997.tb00327.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00327.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 3","pages":"260-277"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00327.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87967525","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}

{"title":"The Ninth Annual Meeting of the Winter Conference on Neural Plasticity","authors":"Ted L. Petit","doi":"10.1111/j.1527-3458.1997.tb00333.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00333.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 4","pages":"363-371"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00333.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81458543","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}

{"title":"Pharmacological Characterization of RJR-2403: A Nicotinic Agonist with Potential Therapeutic Benefit in the Treatment of Alzheimer's Disease","authors":"M. Bencherif,&nbsp;G. Byrd,&nbsp;W. S. Caldwell,&nbsp;J. R. Hayes,&nbsp;P. M. Lippiello","doi":"10.1111/j.1527-3458.1997.tb00331.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00331.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 4","pages":"325-345"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00331.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91271261","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}

{"title":"Cognition Enhancing Profile of CR 2249, a New NMDA-Glycine Site Modulator","authors":"Marco Lanza,&nbsp;Francesco Makovec","doi":"10.1111/j.1527-3458.1997.tb00326.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00326.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 3","pages":"245-259"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00326.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88024281","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}

{"title":"A Review of the Preclinical Development of Zaleplon, a Novel Non-Benzodiazepine Hypnotic for the Treatment of Insomnia","authors":"B. Beer,&nbsp;D. E. Clody,&nbsp;R. Mangano,&nbsp;M. Levner,&nbsp;P. Mayer,&nbsp;J. E. Barrett","doi":"10.1111/j.1527-3458.1997.tb00324.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00324.x","url":null,"abstract":"<div>\u0000 \u0000 <p>Zaleplon (N-[3-(3-cyanopyrazolo[l,5-a]pyrimidin-7-y l)phenyl)]-N-ethylacetamide) is a non-benzodiazepine sedative-hypnotic with benzodiazepine-like sedative effects, but with less apparent liability for accompanying undesirable side effects. Zaleplon displaces [³H]flunitrazepam from rat cortical membranes with an IC₅₀ value of 200 nM and enhances t-butylbicyclophosphorothionate [³⁵S]TBPS binding by 73%, suggesting pharmacological activity mediated by the GABA_A benzodiazepine receptor complex. In various preclinical procedures such as motor activity, muscle relaxation, EEG, anticonvulsant activity, and vigilance, zaleplon produced effects similar to those of other sedative-hypnotic compounds such as triazolam and flurazepam; furthermore, these effects, when evaluated, were reversed by the benzodiazepine receptor antagonist flumazenil. Zaleplon increased punished (conflict) responding in squirrel monkeys and rats and these effects were also antagonized by flumazenil. When established as a discriminative stimulus in rats at 3.0mg/kg i.p., zaleplon showed a dose-related increase in drug-appropriate responding up to the training dose and a correlated decrease in response rate. Triazolam (0.1 to 1.0 mg/kg), the benzodiazepine partial agonist Ro 17-1812 (0.3 to 3.0mg/kg), and the triazolopyridine CL 218,872 (1.0 to 3.0 mg/kg) substituted consistently for zaleplon in all rats, whereas the imidazo-pyridines zolpidem (3.0 to 10 mg/kg) and alpidem (10 to 30 mg/kg), the benzodiazepine partial agonist bretazenil (0.03 to 10 mg/kg) and the novel putative anxio-lytic CL 273,547 (10 to 56 mg/kg) did not result in consistent drug-appropriate responding in all rats. These results suggest that the effects of zaleplon are similar in many respects to other compounds acting at the benzodiazepine receptor complex but differ as well from both benzodiazepine and non- benzodiazepine drugs. This profile of activity, coupled with additional information in ancillary procedures, yields a pre-clinical profile of a short-acting sedative-hypnotic non-benzodiazepine that is currently in Phase III development for the treatment of sleep disturbances.</p>\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 3","pages":"207-224"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00324.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83596114","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}

{"title":"3-α-tropanyl 2-(4-Cl-phenoxy)butyrate (SM 21): A Review of the Pharmacological Profile of a Novel Enhancer of Cholinergic Transmission","authors":"C. Ghelardini,&nbsp;N. Galeotti,&nbsp;F. Gualtieri,&nbsp;S. Scapecchi,&nbsp;A. Bartolini","doi":"10.1111/j.1527-3458.1997.tb00332.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00332.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 4","pages":"346-362"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00332.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72745611","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}

{"title":"Involvement of Calpain Activation in Neurodegenerative Processes","authors":"Antoni Camins,&nbsp;Ester Verdaguer,&nbsp;Jaume Folch,&nbsp;Mercè Pallàs","doi":"10.1111/j.1527-3458.2006.00135.x","DOIUrl":"10.1111/j.1527-3458.2006.00135.x","url":null,"abstract":"<div>\u0000 \u0000 <p>One of the challenges in the coming years will be to better understand the mechanisms of neuronal cell death with the objective of developing adequate drugs for the treatment of neurodegenerative disorders. Caspases and calpains are among the best-characterized cysteine proteases activated in brain disorders. Likewise, during the last decade, extensive research revealed that the deregulation of calpains activity is a key cytotoxic event in a variety of neurodegenerative disorders. Moreover, interest in the role of calpain in neurodegenerative processes is growing due to implication of the involvement of cdk5 in neurodegenerative diseases. Since calpain inhibitors appear to not only protect brain tissue from ischemia, but also to prevent neurotoxicity caused by such neurotoxins as β-amyloid or 3-nitropropionic acid, the currently available data suggest that calpain and cdk5 play a key role in neuronal cell death. It seems clear that the inappropriate activation of cysteine proteases occurs not only during neuronal cell death, but may also contribute to brain pathology in ischemia and traumatic brain disorders. Pharmacological modulation of calpain activation may, therefore, be useful in the treatment of neurodegenerative disorders. It is possible, although difficult, to develop synthetic inhibitors of cysteine proteases, specifically calpains. The inhibition of calpain activation has recently emerged as a potential therapeutic target for the treatment of neurodegenerative diseases.</p>\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 2","pages":"135-148"},"PeriodicalIF":0.0,"publicationDate":"2006-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00135.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26242149","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}

{"title":"A-85380: A Pharmacological Probe for the Preclinical and Clinical Investigation of the α4β2 Neuronal Nicotinic Acetylcholine Receptor","authors":"Lynne E. Rueter,&nbsp;Diana L. Donnelly-Roberts,&nbsp;Peter Curzon,&nbsp;Clark A. Briggs,&nbsp;David J. Anderson,&nbsp;Robert S. Bitner","doi":"10.1111/j.1527-3458.2006.00100.x","DOIUrl":"10.1111/j.1527-3458.2006.00100.x","url":null,"abstract":"<div>\u0000 \u0000 <p>A-85380 [3-(2(s)-azetidinylmethoxy) pyridine] is a neuronal nicotinic acetylcholine receptor (nAChR) agonist that has been a useful tool in the investigation of the function of nAChRs in both preclinical and clinical studies. Amongst nAChR subtypes, A-85380 shows selectivity for the α₄β₂ vs. the α₇ or α₁β₁δγ nAChRs. In functional in vitro cation flux assays, A-85380 is a potent and full agonist. A-85380 has a broad-spectrum analgesic profile with efficacy in acute, persistent, and neuropathic pain models. As demonstrated using selective nAChR antagonists or α₄ antisense, the α₄β₂ nAChR mediates the analgesic effects of A-85380. Interestingly, the site of action depends upon the type of pain as antinociception is mediated by descending inhibition into the spinal cord whereas anti-allodynia in neuropathic pain is mediated at both central and peripheral sites. Radiolabelled forms of A-85380 have been developed and shown to be safe for use in vivo in humans. In clinical studies using positron and photon emission tomography, marked decreases in α₄β₂ nAChRs have been seen in patients with Parkinson's and Alzheimer's disease. Although not developed as a therapeutic agent, A-85380 has proven to be an important component in the development of novel nAChR ligands for the treatment of pain and other disorders.</p>\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 2","pages":"100-112"},"PeriodicalIF":0.0,"publicationDate":"2006-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00100.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26300004","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}