Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2004.TB00021.X
R. Cacabelos, A. Vallejo, V. Lombardi, L. Fernández-Novoa, V. Pichel
E-SAR-94010 (LipoEsar) is a natural product extracted from the marine species S. pilchardus, by means of non-denaturing biotechnological procedures. The main chemical ingredient of LipoEsar is a lipoprotein (60–80%) whose micelle structure probably mimics that of physiological lipoproteins involved in lipid metabolism. In preclinical studies LipoEsar has shown to be effective in (a) reducing blood cholesterol (Cho), triglyceride (TG), uric acid (UA), and glucose (Glu) levels, as well as liver alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity; (b) enhancing immunological function by regulating both lymphocyte and microglia activity; (c) inducing antioxidant effects mediated by superoxide dismutase activity; and (d) improving cognitive function. Clinical studies have revealed that LipoEsar reduces blood total cholesterol (T-Cho) (20–30%), Glu (5–10%), UA (10–15%), TG (30–50%), ALT and AST, after 1–3 months of treatment at a daily dose of 250–500 mg (t.i.d.). The effect on T-Cho is the result of decreasing LDL-Cho levels and increasing HDL-Cho levels in parallel with an improvement in hepatic protection reflected by reduction in ALT, AST, and GGT activity. Most of these therapeutic effects on the regulation of lipid metabolism tend to show an age-dependent pattern and are also associated with specific genomic profiles in the population. In addition, LipoEsar diminishes the size of xanthelasma plaques by 30–60% after 6–9 months of treatment. Similar effects can be observed on atheromatous plaques on the aortic wall of patients with familial and sporadic hypercholesterolemia. LipoEsar is the first marine biotechnological product with lipoprotein structure displaying hypolipemic activity in blood and tissues acting as a potential neuroprotectant in cerebrovascular disorders and arteriosclerosis. Preliminary studies indicate that the biological activity of LipoEsar is genotype-dependent. Since genetic defects in the APOE gene result in familial dysbetalipoproteinemia or type III hyperlipoproteinemia (HLP-III) with increased plasma Cho and TG as a consequence of impaired clearance of chylomicron and VLDL remnants, in the present paper we have investigated the influence of different APOE genotypes on the therapeutic response of LipoEsar in patients with chronic dyslipemia. The study has been performed in 419 patients (age: 55.24 ± 17.71 years; range: 9–96 years) of both sexes (females: N = 212; age: 57.04 ± 17.68 years; range: 15–96 years; males: N = 207; age: 53.38 ± 17.58
{"title":"E‐SAR‐94010 (LipoEsar®): A Pleiotropic Lipoprotein Compound with Powerful Anti‐atheromatous and Lipid Lowering Effects","authors":"R. Cacabelos, A. Vallejo, V. Lombardi, L. Fernández-Novoa, V. Pichel","doi":"10.1111/J.1527-3458.2004.TB00021.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2004.TB00021.X","url":null,"abstract":"E-SAR-94010 (LipoEsar) is a natural product extracted from the marine species S. pilchardus, by means of non-denaturing biotechnological procedures. The main chemical ingredient of LipoEsar is a lipoprotein (60–80%) whose micelle structure probably mimics that of physiological lipoproteins involved in lipid metabolism. In preclinical studies LipoEsar has shown to be effective in (a) reducing blood cholesterol (Cho), triglyceride (TG), uric acid (UA), and glucose (Glu) levels, as well as liver alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity; (b) enhancing immunological function by regulating both lymphocyte and microglia activity; (c) inducing antioxidant effects mediated by superoxide dismutase activity; and (d) improving cognitive function. Clinical studies have revealed that LipoEsar reduces blood total cholesterol (T-Cho) (20–30%), Glu (5–10%), UA (10–15%), TG (30–50%), ALT and AST, after 1–3 months of treatment at a daily dose of 250–500 mg (t.i.d.). The effect on T-Cho is the result of decreasing LDL-Cho levels and increasing HDL-Cho levels in parallel with an improvement in hepatic protection reflected by reduction in ALT, AST, and GGT activity. Most of these therapeutic effects on the regulation of lipid metabolism tend to show an age-dependent pattern and are also associated with specific genomic profiles in the population. In addition, LipoEsar diminishes the size of xanthelasma plaques by 30–60% after 6–9 months of treatment. Similar effects can be observed on atheromatous plaques on the aortic wall of patients with familial and sporadic hypercholesterolemia. LipoEsar is the first marine biotechnological product with lipoprotein structure displaying hypolipemic activity in blood and tissues acting as a potential neuroprotectant in cerebrovascular disorders and arteriosclerosis. Preliminary studies indicate that the biological activity of LipoEsar is genotype-dependent. Since genetic defects in the APOE gene result in familial dysbetalipoproteinemia or type III hyperlipoproteinemia (HLP-III) with increased plasma Cho and TG as a consequence of impaired clearance of chylomicron and VLDL remnants, in the present paper we have investigated the influence of different APOE genotypes on the therapeutic response of LipoEsar in patients with chronic dyslipemia. The study has been performed in 419 patients (age: 55.24 ± 17.71 years; range: 9–96 years) of both sexes (females: N = 212; age: 57.04 ± 17.68 years; range: 15–96 years; males: N = 207; age: 53.38 ± 17.58","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"72 1","pages":"200-201"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76007708","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00170.X
Huaxi Xu
{"title":"Hormonal Regulation of Alzheimer's â‐amyloid Precursor Protein Processing","authors":"Huaxi Xu","doi":"10.1111/J.1527-3458.2000.TB00170.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00170.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"1 1","pages":"22-23"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76022416","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00144.X
K. Wartiovaara, R. Hoffman, N. Cosby
{"title":"Fifth Annual Promega Neurosciences Symposium: Gene Therapy Approaches to Neurodegenerative Disease Miami Beach, FL, November 6, 1999","authors":"K. Wartiovaara, R. Hoffman, N. Cosby","doi":"10.1111/J.1527-3458.2000.TB00144.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00144.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"48 1","pages":"174-178"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73757283","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2001.TB00200.X
H. Silver
Schizophrenia is a common mental disorder that has an early onset and rates high as a cause of medical disability. Antipsychotic agents are the mainstay of treatment but response is often inadequate. Negative symptoms (disturbances in volition, social interaction and affective functions) are particularly difficult to treat and form a major obstacle to rehabilitation. A promising approach to improve response of negative symptoms has been to add a selective serotonin reuptake inhibitor (SSRI) antidepressant to antipsychotic treatment. This review examines evidence pertaining to the efficacy, tolerability, and safety of the SSRI fluvoxamine, combined with antipsychotic agents, in the treatment of negative symptoms in schizophrenia. Important methodological issues, such as differentiating primary and secondary negative symptoms, are discussed. The balance of available evidence indicates that fluvoxamine can improve primary negative symptoms in chronic schizophrenia patients treated with typical antipsychotics and suggests that it may also do so in some patients treated with clozapine. This combination is generally safe and well tolerated although, as antipsychotic drug concentrations may be elevated, attention to dose and drug monitoring should be considered appropriately. Combination with clozapine may require particular caution because of potential toxicity if serum clozapine levels rise steeply. The fluvoxamine doses effective in augmentation are lower than those usually used to treat depression. Evidence regarding the use of fluvoxamine augmentation to treat phenomena, such as obsessions and aggression, which may be associated with schizophrenia, is also examined. An important goal of future studies will be to define which patient groups can benefit from combined treatment.
{"title":"Fluvoxamine as an adjunctive agent in schizophrenia.","authors":"H. Silver","doi":"10.1111/J.1527-3458.2001.TB00200.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00200.X","url":null,"abstract":"Schizophrenia is a common mental disorder that has an early onset and rates high as a cause of medical disability. Antipsychotic agents are the mainstay of treatment but response is often inadequate. Negative symptoms (disturbances in volition, social interaction and affective functions) are particularly difficult to treat and form a major obstacle to rehabilitation. A promising approach to improve response of negative symptoms has been to add a selective serotonin reuptake inhibitor (SSRI) antidepressant to antipsychotic treatment. This review examines evidence pertaining to the efficacy, tolerability, and safety of the SSRI fluvoxamine, combined with antipsychotic agents, in the treatment of negative symptoms in schizophrenia. Important methodological issues, such as differentiating primary and secondary negative symptoms, are discussed. The balance of available evidence indicates that fluvoxamine can improve primary negative symptoms in chronic schizophrenia patients treated with typical antipsychotics and suggests that it may also do so in some patients treated with clozapine. This combination is generally safe and well tolerated although, as antipsychotic drug concentrations may be elevated, attention to dose and drug monitoring should be considered appropriately. Combination with clozapine may require particular caution because of potential toxicity if serum clozapine levels rise steeply. The fluvoxamine doses effective in augmentation are lower than those usually used to treat depression. Evidence regarding the use of fluvoxamine augmentation to treat phenomena, such as obsessions and aggression, which may be associated with schizophrenia, is also examined. An important goal of future studies will be to define which patient groups can benefit from combined treatment.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"21 1","pages":"283-304"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77842819","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2001.TB00197.X
A. Scriabine
{"title":"30th Annual Meeting of Society for Neuroscience. New Drugs Affecting the Central Nervous System New Orleans, Louisiana, USA November 4–9, 2000","authors":"A. Scriabine","doi":"10.1111/J.1527-3458.2001.TB00197.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00197.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"33 1","pages":"241-248"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90485744","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00180.X
A. Kingston, M. O’Neill, A. Bond, W. H. Jordan, J. Tizzano, K. Griffey, J. A. Johnson, N. Jones, J. Monn, D. Lodge, D. Schoepp
{"title":"Neuroprotective Actions of Novel and Potent Agonists of Group II Metabotropic Glutamate Receptors","authors":"A. Kingston, M. O’Neill, A. Bond, W. H. Jordan, J. Tizzano, K. Griffey, J. A. Johnson, N. Jones, J. Monn, D. Lodge, D. Schoepp","doi":"10.1111/J.1527-3458.2000.TB00180.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00180.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"60 1","pages":"36-37"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91349592","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2001.TB00193.X
S. L. Smith, K. Thompson, B. Sargent, D. Heal
BTS 72664, (R)-7-[1-(4-chlorophenoxy)]ethyl]-1,2,4-triazolo(1,5-alpha)pyrimidine, was identified as a drug development candidate from a research program designed to discover novel, broad-spectrum, non-sedative anticonvulsant drugs. BTS 72664 antagonized bicuculline (BIC)- and maximal electroshock (MES)-induced convulsions with ED(50) values of 1.9 and 47.5 mg/kg p.o., respectively. In rodents, it has a wide spectrum of activity preventing seizures induced by picrotoxin, pentylenetetrazol, i.c.v. 4-aminopyridine or NMDA, and audiogenic seizures in DBA-2 mice and GEPR-9 rats. BTS 72664 was also effective in preventing convulsions in amygdala-kindled rats The lack of sedative potential was predicted on the basis of wide separation between ED(50) in anticonvulsant models and TD(50) for motor impairment in mice in rotating rod and inverted horizontal grid tests. BTS 72664 is likely to produce its anticonvulsant effect by enhancing chloride currents through picrotoxin-sensitive chloride channels, and by weak inhibition of Na(+) and NMDA channels. It does not act, however, at the benzodiazepine binding site. In addition to its potential use in the treatment of epilepsy BTS 72664 may be useful in the treatment of stroke. At 50 mg/kg p.o. x 4, given to rats at 12 hourly intervals, starting at 15 min after permanent occlusion of middle cerebral artery (MCA), it reduced cerebral infarct size by 31% (measured at 2 days after insult) and accelerated recovery in a functional behavioral model. BTS 72664 prevented increases in extraneuronal concentrations of glutamate, glycine and serine brain levels induced by a cortical insult to rats (cf. cortical spreading depression). It may, therefore, have also antimigraine activity.
{"title":"BTS 72664-- a novel CNS drug with potential anticonvulsant, neuroprotective, and antimigraine properties.","authors":"S. L. Smith, K. Thompson, B. Sargent, D. Heal","doi":"10.1111/J.1527-3458.2001.TB00193.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2001.TB00193.X","url":null,"abstract":"BTS 72664, (R)-7-[1-(4-chlorophenoxy)]ethyl]-1,2,4-triazolo(1,5-alpha)pyrimidine, was identified as a drug development candidate from a research program designed to discover novel, broad-spectrum, non-sedative anticonvulsant drugs. BTS 72664 antagonized bicuculline (BIC)- and maximal electroshock (MES)-induced convulsions with ED(50) values of 1.9 and 47.5 mg/kg p.o., respectively. In rodents, it has a wide spectrum of activity preventing seizures induced by picrotoxin, pentylenetetrazol, i.c.v. 4-aminopyridine or NMDA, and audiogenic seizures in DBA-2 mice and GEPR-9 rats. BTS 72664 was also effective in preventing convulsions in amygdala-kindled rats The lack of sedative potential was predicted on the basis of wide separation between ED(50) in anticonvulsant models and TD(50) for motor impairment in mice in rotating rod and inverted horizontal grid tests. BTS 72664 is likely to produce its anticonvulsant effect by enhancing chloride currents through picrotoxin-sensitive chloride channels, and by weak inhibition of Na(+) and NMDA channels. It does not act, however, at the benzodiazepine binding site. In addition to its potential use in the treatment of epilepsy BTS 72664 may be useful in the treatment of stroke. At 50 mg/kg p.o. x 4, given to rats at 12 hourly intervals, starting at 15 min after permanent occlusion of middle cerebral artery (MCA), it reduced cerebral infarct size by 31% (measured at 2 days after insult) and accelerated recovery in a functional behavioral model. BTS 72664 prevented increases in extraneuronal concentrations of glutamate, glycine and serine brain levels induced by a cortical insult to rats (cf. cortical spreading depression). It may, therefore, have also antimigraine activity.","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"24 1","pages":"146-71"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90723400","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2000.TB00163.X
R. Deth
{"title":"D4 Dopamine Receptors and the Molecular Mechanism of Attention","authors":"R. Deth","doi":"10.1111/J.1527-3458.2000.TB00163.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2000.TB00163.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"30 11-12","pages":"9-10"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91508935","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}
Pub Date : 2006-06-07DOI: 10.1111/J.1527-3458.2004.TB00015.X
M. O'Neill, M. Maćkowiak, V. Lakics, C. Hicks, D. Bleakman, P. Skolnick
{"title":"The AMPA Receptor Potentiator, LY404187 Modulates Expression of Neurotrophins: in vitro and in vivo Studies in Cortical and Hippocampal Brain Regions","authors":"M. O'Neill, M. Maćkowiak, V. Lakics, C. Hicks, D. Bleakman, P. Skolnick","doi":"10.1111/J.1527-3458.2004.TB00015.X","DOIUrl":"https://doi.org/10.1111/J.1527-3458.2004.TB00015.X","url":null,"abstract":"","PeriodicalId":10499,"journal":{"name":"CNS drug reviews","volume":"22 1","pages":"193-193"},"PeriodicalIF":0.0,"publicationDate":"2006-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84663614","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：