CNS drug reviews最新文献

{"title":"2-(2-aminoethyl)-quinoline (D-1997): A Novel Agonist at Craniovascular 5-HT1 Receptors Relevant to Migraine Therapy","authors":"J. Terron","doi":"10.1111/J.1527-3458.2000.TB00152.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00152.X","url":null,"abstract":"The functional pharmacological properties of a group of quinoline-derivatives were screened for agonist activity at 5-HT1-like receptors mediating vasoconstriction. In experimental models predictive of antimigraine activity, 2-(2-aminoethyl) quinoline hydrochloride (D-1997) exhibited higher potency and efficacy at vasoconstrictor 5-HT1-like receptors than quipazine. D-1997 was also found to activate a novel vasoconstrictor mechanism in the carotid circulation. It is suggested D-1997 may represent a useful lead in the search for better acute antimigraine therapies.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"14 1","pages":"267-277"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91256937","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}

{"title":"Activation of M1 Muscarinic Receptors by AF267B Protects Hippocampal Neurons from Amyloid β Peptide Toxicity by Acting on the WNT Signalling","authors":"G. Farías, A. Fisher, N. Inestrosa","doi":"10.1111/J.1527-3458.2004.TB00019.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2004.TB00019.X","url":null,"abstract":"A loss of pre-synaptic cholinergic neurons, as observed in Alzheimer’s disease (AD), may lead to a decrease in M1 muscarinic receptor-mediated signaling. This, in turn, may affect an amyloid precursor protein processing and tau phosphorylation, two major features of AD. Defects in Wnt signaling have been postulated to contribute to the pathogenesis of the disease. How Wnt signaling may play a role in AD pathology remains to be elucidated. We report here that the activation of M1 receptor, by the M1 agonist AF267B, protects hippocampal neurons from amyloid-â-peptide and this effect involves the Wnt signaling pathway. The studies were carried out in primary cultures of rat hippocampal neurons, in the presence and absence of amyloid-â-peptide; plus and minus AF267B with and without pirenzepine, a selective M1 antagonist. Results indicate that AF267B protects neuronal cells as evaluated by the MTT reduction, immunofluorescence of neurofilaments and apoptotic analysis. To evaluate the role of the Wnt pathway on neuroprotection, we studied the stabilization of cytoplasmic and nuclear â-catenin, glycogen synthase kinase3-â activity as well as the expression of Wnt target genes. Results show that the neuroprotection induced by AF267B but not by the antagonist pirenzepine on the M1 mAChR is accomplished by the activation of the Wnt signaling pathway. We conclude that the cross talk between the M1 receptor signaling and the Wnt components underlie the neuroprotective effect of the M1 muscarinic agonist AF267B on rat hippocampal neurons. This may be highly relevant in the treatment of AD with M1 agonists. Supported by FONDAP-Biomedicine (No. 13980001) and Millennium Institute (MIFAB).","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"61 1","pages":"197-197"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78128755","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}

{"title":"Strategic Issues in the Discovery of Cognitive Enhancers","authors":"G. Rose","doi":"10.1111/J.1527-3458.2000.TB00159.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00159.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"8 1","pages":"3-3"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75389906","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}

{"title":"SB-236057-A: a selective 5-HT1B receptor inverse agonist.","authors":"C. Roberts, J. Watson, Gary W. Price, D. Middlemiss","doi":"10.1111/J.1527-3458.2001.TB00209.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00209.X","url":null,"abstract":"5-HT1B autoreceptors are involved in the control of extracellular 5-HT levels from both the terminal and cell body regions of serotonergic neurons. In this manuscript we review the pharmacological and pharmacokinetic data available for the selective and potent 5-HT1B receptor inverse agonist, SB-236057-A (1'-ethyl-5-(2'-methyl-4'-(5-methyl-1,3,4-oxadiazolyl-2-yl)biphenyl-4-carbonyl)-2,3,6,7-tetrahydrospiro (furo[2,3-f]indole-3,4'-piperidine) hydrochloride). SB 236057-A has been shown to have high affinity for human 5-HT1B receptors (pK(i) = 8.2) and displays 80 or more fold selectivity for the human 5-HT1B receptor over other 5-HT receptors and a range of additional receptors, ion channels and enzymes. In functional studies at human 5-HT1B receptors SB-236057-A displayed inverse agonism (pA(2) = 8.9) using [(35)S]GTPgammaS binding, and silent antagonism (pA(2) = 9.2) using cAMP accumulation. SB-236057-A also acted as an antagonist at the 5-HT terminal autoreceptor as measured by [3H]5-HT release from electrically stimulated guinea pig and human cortical slices. In the guinea pig, pharmacokinetic analysis demonstrated that SB-236057-A was bioavailable and according to in vivo pharmacodynamic assays it enters brain and has a long duration of action. Importantly no side effect liability was evident at relevant doses from anxiogenic, cardiovascular, sedative or migraine viewpoints. In vivo microdialysis studies demonstrated that SB-236057-A is an antagonist in the guinea pig cortex but has no effect on extracellular 5-HT levels per se. In contrast, SB-236057-A increased extracellular 5-HT levels in the guinea pig dentate gyrus. This increase in 5-HT release was comparable to that observed after 14 days of paroxetine administration. SB-236057-A has been a useful tool in confirming that, in either guinea pigs or humans, the terminal 5-HT autoreceptor is of the 5-HT1B subtype. It appears that acute 5-HT1B receptor blockade, by virtue of increased 5-HT release in the dentate gyrus, may provide a rapidly acting antidepressant.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"28 1","pages":"433-44"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73631168","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}

{"title":"Thirty‐fifth Annual Meeting of Society for Neuroscience Washington, D.C., USA November 12–16, 2005.","authors":"A. Scriabine","doi":"10.1111/J.1527-3458.2005.TB00057.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2005.TB00057.X","url":null,"abstract":"Keywords: \u0000 \u0000ALS; \u0000Alzheimer's disease; \u0000Anticonvulsants; \u0000Antidepressants; \u0000Cannabinoids; \u0000Drug addiction; \u0000Huntington's disease, Neuroprotective drugs; \u0000Parkinson's disease","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"141 1","pages":"408-418"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76814592","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}

{"title":"Recent developments in the discovery of novel adenosine kinase inhibitors: mechanism of action and therapeutic potential.","authors":"S. McGaraughty, M. Cowart, M. Jarvis","doi":"10.1111/J.1527-3458.2001.TB00208.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00208.X","url":null,"abstract":"Adenosine (ADO) is an endogenous inhibitory neuromodulator that limits cellular excitability in response to tissue trauma and inflammation. Adenosine kinase (AK; EC 2.7.1.20) is the primary metabolic enzyme regulating intra- and extracellular concentrations of ADO. AK inhibitors have been shown to significantly increase ADO concentrations at sites of tissue injury and to provide effective antinociceptive, antiinflammatory, and anticonvulsant activity in animal models. Structurally novel nucleoside and non-nucleoside AK inhibitors that demonstrate high specificity for the AK enzyme compared with other ADO metabolic enzymes, transporters, and receptors have recently been synthesized. These compounds have also demonstrated improved cellular and tissue penetration compared with earlier tubercidin analogs. These compounds have been shown to exert beneficial effects in animal models of pain, inflammation and epilepsy with reduced cardiovascular side effects compared with direct acting ADO receptor (P1) agonists, thus supporting the hypothesis that AK inhibitors can enhance the actions of ADO in a site- and event-specific fashion.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"110 1","pages":"415-32"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87691215","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}

{"title":"Cell Transplantation Strategies to Repair the Injured Spinal Cord","authors":"J. D. Kocsis","doi":"10.1111/J.1527-3458.2000.TB00184.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00184.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"15 1","pages":"41-41"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89624105","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}

{"title":"Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data.","authors":"W. J. Giardina, Michael Williams","doi":"10.1111/J.1527-3458.2001.TB00201.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00201.X","url":null,"abstract":"Adrogolide (ABT-431; DAS-431) is a chemically stable prodrug that is converted rapidly (<1 min) in plasma to A-86929, a full agonist at dopamine D1 receptors. In in vitro functional assays, A-86929 is over 400 times more selective for dopamine D1 than D2 receptors. In rats with a unilateral loss of striatal dopamine, A-86929 produces contralateral rotations that are inhibited by dopamine D1 but not by dopamine D2 receptor antagonists. Adrogolide improves behavioral disability and locomotor activity scores in MPTP-lesioned marmosets, a model of Parkinson's disease (PD), and shows no tolerance upon repeated dosing for 28 days. In PD patients, intravenous (i.v.) adrogolide has antiparkinson efficacy equivalent to that of L-DOPA with a tendency towards a reduced liability to induce dyskinesia. The adverse events associated with its use were of mild-to-moderate severity and included injection site reaction, asthenia, headache, nausea, vomiting, postural hypotension, vasodilitation, and dizziness. Adrogolide can also attenuate the ability of cocaine to induce cocaine-seeking behavior and does not itself induce cocaine-seeking behavior in a rodent model of cocaine craving and relapse. In human cocaine abusers, i.v. adrogolide reduces cocaine craving and other cocaine-induced subjective effects. The results of animal abuse liability studies indicate that adrogolide is unlikely to have abuse potential in man. Adrogolide has also been reported to reverse haloperidol-induced cognitive deficits in monkeys, suggesting that it may be an effective treatment for the cognitive dysfunction associated with aging and disease. Adrogolide undergoes a high hepatic \"first-pass\" metabolism in man after oral dosing and, as a result, has a low oral bioavailability (approximately 4%). This limitation may potentially be circumvented by oral inhalation formulations for intrapulmonary delivery that greatly increase the bioavailability of adrogolide. As the first full dopamine D1 receptor agonist to show efficacy in PD patients and to reduce the craving and subjective effects of cocaine in cocaine abusers, adrogolide represents an important tool in understanding the pharmacotherapeutic potential of dopamine D1 receptor agonists.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"40 1","pages":"305-16"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77756823","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}

{"title":"Hu 210: a potent tool for investigations of the cannabinoid system.","authors":"A. Ottani, D. Giuliani","doi":"10.1111/J.1527-3458.2001.TB00192.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00192.X","url":null,"abstract":"The synthetic compound HU 210 displays a multiplicity of biochemical, pharmacological, and behavioral effects, most of which have been demonstrated to be dependent on a selective agonistic activity at CB(1) and CB(2) cannabinoid receptors and to involve the main neurotransmitter systems. Results obtained in various studies suggest a potential clinical application of this highly potent drug (e.g., as antipyretic, antiinflammatory, analgesic, antiemetic, and antipsychotic agent) as well as its usefulness in research aimed to develop a better understanding of the involvement of the endogenous cannabinoid system in a number of physiopathological functions.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"9 1","pages":"131-45"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74413913","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}

{"title":"Alzheimer's disease, cancer and the search for a better aspirin. Postgraduate course at Mount Sinai School of Medicine, New York, NY June 22-23, 2001.","authors":"A. Scriabine","doi":"10.1111/J.1527-3458.2001.TB00203.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00203.X","url":null,"abstract":"The meeting was organized and chaired by Giulio Maria Pasinetti, Associate Professor of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA. It was attended by ca. 150 physicians and basic medical scientists and consisted of 23 presentations on the effects of non-steroidal antiinflammatory drugs (NSAIDs), primarily cyclooxygenase 2 (COX-2) inhibitors, in Alzheimer’s disease (AD) and cancer. The meeting was supported by grants from Merck & Co. and Helsinn Healthcare. In his introductory remarks Pasinetti pointed out that there is substantial evidence that NSAIDs protect from colon cancer. They may also slow the progression of Alzheimer’s disease. He expressed hope that this meeting will provide an impetus for further evaluation and eventual use of NSAIDs in the therapy of these diseases. The first lecture, “Building a Better Aspirin, Experimental Approaches and Clinical Implications,” was delivered by D. L. DeWitt (Michigan State Univ., Lansing, MI, USA). He emphasized the importance of selective inhibition of COX-2 isoenzyme for side effect profile of inhibitors. Minor changes in the amino acid composition of COX-2, as compared to COX-1, increase the binding site pocket. Inhibitors with bulky side groups are more selective for COX-2 because they fit better to the larger binding site pocket. COX-2 inhibitors, unlike COX-1, do not require acidic side group for binding to the isoenzyme. The COX-2 + inhibitor complexes are not easily reversible, whereas binding of the inhibitors to COX-1 is freely reversible. There are also different modes of inhibition: time-dependent and competitive. Selective COX-2 inhibitors inhibit the isoenzyme time-dependently, the degree of inhibition increases with time. The same inhibitors may inhibit COX-1 competitively. At a low dose, aspirin is a selective COX-1 inhibitor. Among new COX-2 inhibitors valdeco-","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"50 1","pages":"346-52"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78254065","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}