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Manuela G Lopez - One of the best experts on this subject based on the ideXlab platform.
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effects of memantine and Galantamine given separately or in association on memory and hippocampal neuronal loss after transient global cerebral ischemia in gerbils
Brain Research, 2009Co-Authors: Silvia Lorrio, Pilar Negredo, J M Roda, Antonio G Garcia, Manuela G LopezAbstract:Abstract Galantamine is an acetylcholinesterase inhibitor and memantine is a non competitive antagonist of NMDA receptors that are being used to treat Alzheimer's disease (AD) patients. The fact that drugs with different mechanisms of action are available to treat AD introduces the prospect of prescribing drug combinations to amplify drug efficacy. This study was planed to evaluate the potential neuroprotective effects of Galantamine combined with memantine in a transient global cerebral ischemia model in gerbils. Animal groups included in the study were: sham, ischemia, and ischemia plus Galantamine (1 mg/kg and 10 mg/kg), memantine (10 mg/kg and 20 mg/kg), 1 mg/kg Galantamine plus 10 mg/kg memantine, and 10 mg/kg Galantamine plus 10 mg/kg memantine, respectively. Surviving pyramidal neurons in the CA1 subfield of the hippocampus, TUNEL, caspase-3 and SOD-2 immunohistochemistries, and the object placement test were evaluated 72 h after reperfusion. Memantine did not exert a clear neuroprotective effect, nor did it prevent spatial memory loss. In a previous study using the same experimental model, Galantamine was neuroprotective and improved spatial memory. In this study, the association of 10 mg/kg memantine with 10 mg/kg Galantamine increased the number of living pyramidal neurons, reduced TUNEL, active caspase-3 and SOD-2 immunoreactivity, and preserved spatial memory after ischemia-reperfusion injury; however, the effects of the combination were not statistically different from those observed in animals treated with Galantamine alone. We believe these results are of interest from a clinical point of view because the association of both drugs is being used in clinical practice and in clinical trials to treat Alzheimer's disease and vascular dementia.
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Galantamine postischemia provides neuroprotection and memory recovery against transient global cerebral ischemia in gerbils
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Silvia Lorrio, J M Roda, Antonio G Garcia, Monica Sobrado, Esperanza Arias, Manuela G LopezAbstract:Galantamine, currently used in Alzheimer9s patients, has shown neuroprotection in hippocampal slices subjected to oxygenglucose deprivation. Here, we present an in vivo study to evaluate the potential neuroprotective effects of Galantamine in a transient global cerebral ischemia model in gerbils. Three treatment protocols were used. In the pretreatment protocol, gerbils were treated before ischemia and for 3 consecutive days thereafter. Eight groups of animals were included: sham operation plus placebo, 10 mg/kg mecamylamine and 10 mg/kg Galantamine, respectively; and ischemia plus placebo, 10 mg/kg mecamylamine, 1 mg/kg Galantamine, and 10 mg/kg Galantamine and 10 mg/kg mecamylamine plus Galantamine, respectively. Postischemia protocols included three groups of animals: sham operation, ischemia plus placebo, and ischemia plus 10 mg/kg Galantamine; substances were administered 3 or 6 h after ischemia and for 2 consecutive days thereafter. Pyramidal neurons surviving in the cornus ammonis 1 region of the hippocampus were evaluated 72 h after reperfusion, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) histochemistry, caspase-3 and superoxide dismutase (SOD)-2 immunohistochemistries, and Western blottings were performed, and object placement tests were carried out. Galantamine significantly increased the number of living pyramidal neurons after ischemia-reperfusion injury. Galantamine significantly reduced TUNEL, active caspase-3, and SOD-2 immunoreactivity. The nicotinic antagonist mecamylamine blocked the protective effects of Galantamine. The neuroprotective effects of Galantamine were preserved even when first administered at 3 h postischemia. These results correlated with the performance in the object placement test. This study shows that Galantamine provides in vivo neuroprotection and memory recovery against global cerebral ischemia, even when administration begins 3 h postischemia.
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unequal neuroprotection afforded by the acetylcholinesterase inhibitors Galantamine donepezil and rivastigmine in sh sy5y neuroblastoma cells role of nicotinic receptors
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Esperanza Arias, Antonio G Garcia, Mercedes Villarroya, Sonia Gallegosandin, Manuela G LopezAbstract:Donepezil, rivastigmine, and Galantamine are three drugs with acetylcholinesterase (AChE)-inhibiting activity that are currently being used to treat patients suffering from Alzheimer's disease. We have studied the neuroprotective effects of these drugs, in comparison with nicotine, on cell death caused by beta-amyloid (Abeta) and okadaic acid, two models that are relevant to Alzheimer's pathology, in the human neuroblastoma cell line SH-SY5Y. Galantamine and donepezil showed a U-shaped neuroprotective curve against okadaic acid toxicity; maximum protection was achieved at 0.3 microM Galantamine and at 1 microM donepezil; at higher concentrations, protection was diminished. Rivastigmine showed a concentration-dependent effect; maximum protection was achieved at 3 microM. When apoptosis was induced by Abeta25-35, Galantamine, donepezil, and rivastigmine showed maximum protection at the same concentrations: 0.3, 1, and 3 microM, respectively. Nicotine also afforded protection against Abeta- and okadaic acid-induced toxicity. The neuroprotective effects of Galantamine, donepezil, and nicotine were reversed by the alpha7 nicotinic antagonist methyllycaconitine but not by the alpha4beta2 nicotinic antagonist dihydro-beta-erythroidine. The phosphoinositide 3-kinase (PI3K)-Akt blocker 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) reversed the protective effects of Galantamine, donepezil, and nicotine but not that of rivastigmine. In contrast, the bcl-2 antagonist ethyl[2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)]-4H-chromene-3-carboxylate (HA 14-1) reversed the protective effects of the three AChE inhibitors and that of nicotine. Our results show that Galantamine, donepezil, and rivastigmine afford neuroprotection through a mechanism that is likely unrelated to AChE inhibition. Such neuroprotection seemed to be linked to alpha7 nicotinic receptors and the PI3K-Akt pathway in the case of Galantamine and donepezil but not for rivastigmine.
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Galantamine prevents apoptosis induced by β-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors
Neuropharmacology, 2004Co-Authors: Esperanza Arias, Antonio G Garcia, Eva Alés, Nelson H. Gabilan, María F. Cano-abad, Mercedes Villarroya, Manuela G LopezAbstract:Galantamine is currently used to treat Alzheimer's disease patients; it behaves as a mild blocker of acetylcholinesterase (AChE) and has an allosteric modulating action on nicotinic acetylcholine receptors (nAChRs). In this study, we observed that Galantamine prevented cell death induced by the peptide beta-amyloid(1-40) and thapsigargin in the human neuroblastoma cell line SH-SY5Y, as well as in bovine chromaffin cells. The protective effect of Galantamine was concentration-dependent in both cell types; maximum protection was produced at 300 nM. The antiapoptotic effect of Galantamine at 300 nM, against beta-amyloid(1-40) or thapsigargin-induced toxicity, was reversed by alpha-bungarotoxin. At neuroprotective concentrations, Galantamine caused a mild and sustained elevation of the cytosolic concentration of calcium, [Ca2+]c, measured in single cells loaded with Fura-2. Incubation of the cells for 48 h with 300 nM Galantamine doubled the density of alpha7 nicotinic receptors and tripled the expression of the antiapoptotic protein Bcl-2. These results strongly suggest that Galantamine can prevent apoptotic cell death by inducing neuroprotection through a mechanism related to that described for nicotine, i.e. activation of nAChRs and upregulation of Bcl-2. These findings might explain the long-term beneficial effects of Galantamine in patients suffering of Alzheimer's disease.
David Craig - One of the best experts on this subject based on the ideXlab platform.
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The Cochrane Library - Galantamine for vascular cognitive impairment.
The Cochrane database of systematic reviews, 2006Co-Authors: Jacqueline Birks, David CraigAbstract:Background Vascular dementia represents the second most common type of dementia after that caused by Alzheimer's disease. Particularly in older patients, the combination of vascular dementia and Alzheimer's disease is common and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all patients fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss and the term vascular cognitive impairment is more useful. Currently, no established standard treatment for vascular cognitive impairment exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and vascular cognitive impairment raising the possibility that cholinesterase inhibitors such as Galantamine may be beneficial for the latter. Objectives To assess the efficacy of Galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or mixed dementia. Search methods The trials were identified from a search of ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 12 January 2013. The register contains information on trials identified from frequent searches of a number of major healthcare and medical databases (MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS) as well as from a number of international and national trial registries and grey literature sources. The terms used were: Galantamine, galanthamine, Reminyl, Razadyne, Nivalin. Selection criteria All unconfounded randomised double-blind trials comparing Galantamine with placebo were eligible for inclusion. Data collection and analysis Two review authors independently extracted the data from included studies. Main results Two trials, 1378 participants, employing randomised, double-blind, parallel-group methodology were included. Both trials were of six months duration and were testing a Galantamine dose of 16-24 mg/day in two divided doses. Both trials had an overall low risk of bias. The GAL-INT-6 trial included 592 patients with vascular dementia diagnosed according to recognised criteria and patients with Alzheimer's disease and coincidental radiographic findings of cerebrovascular disease. Limited outcome data were reported for the subgroup data with vascular dementia. In the whole trial population, statistically significant treatment effects in favour of Galantamine compared with placebo in cognition (ADAS-cog, mean difference (MD) -2.29, 95% confidence interval (CI) -3.46 to -1.12, P = 0.0001 ), activities of daily living (DAD, MD 4.10, 95% CI 1.25 to 6.95, P = 0.005) and behaviour (NPI, MD -2.06, 95% CI -4.09 to -0.03, P = 0.05 ) were noted. Significantly higher numbers of patients dropped out, (102/396 Galantamine, 33/196 placebo odds ratio (OR) 1.71, 95% CL 1.11 to 2.65, P = 0.02) and withdrew due to an adverse event from the group treated with Galantamine compared with the placebo group (79/396 Galantamine, 16/196 placebo, OR 2.80, 95% CI 1.59 to 4.95, P =0.0004). Data were also included from a second larger trial (GAL-INT-26) involving 788 patients with vascular dementia diagnosed using standard criteria. Statistically significant benefits favouring Galantamine over placebo in assessments of cognition (ADAS-cog, MD -1.50, 95% CI -2.39 to -0.61, P = 0.0009), and favouring placebo compared with Galantamine for behaviour (NPI, MD 1.80, 95% CI 0.29 to 3.31, P = 0.02) are recorded. Significantly higher numbers of patients dropped out from the group treated with Galantamine compared with the placebo group (50/396 Galantamine, 25/390 placebo OR 2.11, 95% CL 1.28 to 3.49, P = 0.004). Authors' conclusions Limited data were available when considering the impact of Galantamine on vascular dementia or vascular cognitive impairment. The data available suggest some advantage over placebo in the areas of cognition and global clinical state. In both included trials Galantamine produced higher rates of gastrointestinal side-effects. More studies are needed before firm conclusions can be drawn.
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Galantamine for vascular cognitive impairment
Cochrane Database of Systematic Reviews, 2006Co-Authors: Jacqueline Birks, David CraigAbstract:Background Vascular dementia represents the second most common type of dementia after that caused by Alzheimer's disease. Particularly in older patients, the combination of vascular dementia and Alzheimer's disease is common and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all patients fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss and the term vascular cognitive impairment is more useful. Currently, no established standard treatment for vascular cognitive impairment exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and vascular cognitive impairment raising the possibility that cholinesterase inhibitors such as Galantamine may be beneficial for the latter. Objectives To assess the efficacy of Galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or mixed dementia. Search methods The trials were identified from a search of ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 12 January 2013. The register contains information on trials identified from frequent searches of a number of major healthcare and medical databases (MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS) as well as from a number of international and national trial registries and grey literature sources. The terms used were: Galantamine, galanthamine, Reminyl, Razadyne, Nivalin. Selection criteria All unconfounded randomised double-blind trials comparing Galantamine with placebo were eligible for inclusion. Data collection and analysis Two review authors independently extracted the data from included studies. Main results Two trials, 1378 participants, employing randomised, double-blind, parallel-group methodology were included. Both trials were of six months duration and were testing a Galantamine dose of 16-24 mg/day in two divided doses. Both trials had an overall low risk of bias. The GAL-INT-6 trial included 592 patients with vascular dementia diagnosed according to recognised criteria and patients with Alzheimer's disease and coincidental radiographic findings of cerebrovascular disease. Limited outcome data were reported for the subgroup data with vascular dementia. In the whole trial population, statistically significant treatment effects in favour of Galantamine compared with placebo in cognition (ADAS-cog, mean difference (MD) -2.29, 95% confidence interval (CI) -3.46 to -1.12, P = 0.0001 ), activities of daily living (DAD, MD 4.10, 95% CI 1.25 to 6.95, P = 0.005) and behaviour (NPI, MD -2.06, 95% CI -4.09 to -0.03, P = 0.05 ) were noted. Significantly higher numbers of patients dropped out, (102/396 Galantamine, 33/196 placebo odds ratio (OR) 1.71, 95% CL 1.11 to 2.65, P = 0.02) and withdrew due to an adverse event from the group treated with Galantamine compared with the placebo group (79/396 Galantamine, 16/196 placebo, OR 2.80, 95% CI 1.59 to 4.95, P =0.0004). Data were also included from a second larger trial (GAL-INT-26) involving 788 patients with vascular dementia diagnosed using standard criteria. Statistically significant benefits favouring Galantamine over placebo in assessments of cognition (ADAS-cog, MD -1.50, 95% CI -2.39 to -0.61, P = 0.0009), and favouring placebo compared with Galantamine for behaviour (NPI, MD 1.80, 95% CI 0.29 to 3.31, P = 0.02) are recorded. Significantly higher numbers of patients dropped out from the group treated with Galantamine compared with the placebo group (50/396 Galantamine, 25/390 placebo OR 2.11, 95% CL 1.28 to 3.49, P = 0.004). Authors' conclusions Limited data were available when considering the impact of Galantamine on vascular dementia or vascular cognitive impairment. The data available suggest some advantage over placebo in the areas of cognition and global clinical state. In both included trials Galantamine produced higher rates of gastrointestinal side-effects. More studies are needed before firm conclusions can be drawn.
Antonio G Garcia - One of the best experts on this subject based on the ideXlab platform.
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effects of memantine and Galantamine given separately or in association on memory and hippocampal neuronal loss after transient global cerebral ischemia in gerbils
Brain Research, 2009Co-Authors: Silvia Lorrio, Pilar Negredo, J M Roda, Antonio G Garcia, Manuela G LopezAbstract:Abstract Galantamine is an acetylcholinesterase inhibitor and memantine is a non competitive antagonist of NMDA receptors that are being used to treat Alzheimer's disease (AD) patients. The fact that drugs with different mechanisms of action are available to treat AD introduces the prospect of prescribing drug combinations to amplify drug efficacy. This study was planed to evaluate the potential neuroprotective effects of Galantamine combined with memantine in a transient global cerebral ischemia model in gerbils. Animal groups included in the study were: sham, ischemia, and ischemia plus Galantamine (1 mg/kg and 10 mg/kg), memantine (10 mg/kg and 20 mg/kg), 1 mg/kg Galantamine plus 10 mg/kg memantine, and 10 mg/kg Galantamine plus 10 mg/kg memantine, respectively. Surviving pyramidal neurons in the CA1 subfield of the hippocampus, TUNEL, caspase-3 and SOD-2 immunohistochemistries, and the object placement test were evaluated 72 h after reperfusion. Memantine did not exert a clear neuroprotective effect, nor did it prevent spatial memory loss. In a previous study using the same experimental model, Galantamine was neuroprotective and improved spatial memory. In this study, the association of 10 mg/kg memantine with 10 mg/kg Galantamine increased the number of living pyramidal neurons, reduced TUNEL, active caspase-3 and SOD-2 immunoreactivity, and preserved spatial memory after ischemia-reperfusion injury; however, the effects of the combination were not statistically different from those observed in animals treated with Galantamine alone. We believe these results are of interest from a clinical point of view because the association of both drugs is being used in clinical practice and in clinical trials to treat Alzheimer's disease and vascular dementia.
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Galantamine postischemia provides neuroprotection and memory recovery against transient global cerebral ischemia in gerbils
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Silvia Lorrio, J M Roda, Antonio G Garcia, Monica Sobrado, Esperanza Arias, Manuela G LopezAbstract:Galantamine, currently used in Alzheimer9s patients, has shown neuroprotection in hippocampal slices subjected to oxygenglucose deprivation. Here, we present an in vivo study to evaluate the potential neuroprotective effects of Galantamine in a transient global cerebral ischemia model in gerbils. Three treatment protocols were used. In the pretreatment protocol, gerbils were treated before ischemia and for 3 consecutive days thereafter. Eight groups of animals were included: sham operation plus placebo, 10 mg/kg mecamylamine and 10 mg/kg Galantamine, respectively; and ischemia plus placebo, 10 mg/kg mecamylamine, 1 mg/kg Galantamine, and 10 mg/kg Galantamine and 10 mg/kg mecamylamine plus Galantamine, respectively. Postischemia protocols included three groups of animals: sham operation, ischemia plus placebo, and ischemia plus 10 mg/kg Galantamine; substances were administered 3 or 6 h after ischemia and for 2 consecutive days thereafter. Pyramidal neurons surviving in the cornus ammonis 1 region of the hippocampus were evaluated 72 h after reperfusion, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) histochemistry, caspase-3 and superoxide dismutase (SOD)-2 immunohistochemistries, and Western blottings were performed, and object placement tests were carried out. Galantamine significantly increased the number of living pyramidal neurons after ischemia-reperfusion injury. Galantamine significantly reduced TUNEL, active caspase-3, and SOD-2 immunoreactivity. The nicotinic antagonist mecamylamine blocked the protective effects of Galantamine. The neuroprotective effects of Galantamine were preserved even when first administered at 3 h postischemia. These results correlated with the performance in the object placement test. This study shows that Galantamine provides in vivo neuroprotection and memory recovery against global cerebral ischemia, even when administration begins 3 h postischemia.
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unequal neuroprotection afforded by the acetylcholinesterase inhibitors Galantamine donepezil and rivastigmine in sh sy5y neuroblastoma cells role of nicotinic receptors
Journal of Pharmacology and Experimental Therapeutics, 2005Co-Authors: Esperanza Arias, Antonio G Garcia, Mercedes Villarroya, Sonia Gallegosandin, Manuela G LopezAbstract:Donepezil, rivastigmine, and Galantamine are three drugs with acetylcholinesterase (AChE)-inhibiting activity that are currently being used to treat patients suffering from Alzheimer's disease. We have studied the neuroprotective effects of these drugs, in comparison with nicotine, on cell death caused by beta-amyloid (Abeta) and okadaic acid, two models that are relevant to Alzheimer's pathology, in the human neuroblastoma cell line SH-SY5Y. Galantamine and donepezil showed a U-shaped neuroprotective curve against okadaic acid toxicity; maximum protection was achieved at 0.3 microM Galantamine and at 1 microM donepezil; at higher concentrations, protection was diminished. Rivastigmine showed a concentration-dependent effect; maximum protection was achieved at 3 microM. When apoptosis was induced by Abeta25-35, Galantamine, donepezil, and rivastigmine showed maximum protection at the same concentrations: 0.3, 1, and 3 microM, respectively. Nicotine also afforded protection against Abeta- and okadaic acid-induced toxicity. The neuroprotective effects of Galantamine, donepezil, and nicotine were reversed by the alpha7 nicotinic antagonist methyllycaconitine but not by the alpha4beta2 nicotinic antagonist dihydro-beta-erythroidine. The phosphoinositide 3-kinase (PI3K)-Akt blocker 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) reversed the protective effects of Galantamine, donepezil, and nicotine but not that of rivastigmine. In contrast, the bcl-2 antagonist ethyl[2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)]-4H-chromene-3-carboxylate (HA 14-1) reversed the protective effects of the three AChE inhibitors and that of nicotine. Our results show that Galantamine, donepezil, and rivastigmine afford neuroprotection through a mechanism that is likely unrelated to AChE inhibition. Such neuroprotection seemed to be linked to alpha7 nicotinic receptors and the PI3K-Akt pathway in the case of Galantamine and donepezil but not for rivastigmine.
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Galantamine prevents apoptosis induced by β-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors
Neuropharmacology, 2004Co-Authors: Esperanza Arias, Antonio G Garcia, Eva Alés, Nelson H. Gabilan, María F. Cano-abad, Mercedes Villarroya, Manuela G LopezAbstract:Galantamine is currently used to treat Alzheimer's disease patients; it behaves as a mild blocker of acetylcholinesterase (AChE) and has an allosteric modulating action on nicotinic acetylcholine receptors (nAChRs). In this study, we observed that Galantamine prevented cell death induced by the peptide beta-amyloid(1-40) and thapsigargin in the human neuroblastoma cell line SH-SY5Y, as well as in bovine chromaffin cells. The protective effect of Galantamine was concentration-dependent in both cell types; maximum protection was produced at 300 nM. The antiapoptotic effect of Galantamine at 300 nM, against beta-amyloid(1-40) or thapsigargin-induced toxicity, was reversed by alpha-bungarotoxin. At neuroprotective concentrations, Galantamine caused a mild and sustained elevation of the cytosolic concentration of calcium, [Ca2+]c, measured in single cells loaded with Fura-2. Incubation of the cells for 48 h with 300 nM Galantamine doubled the density of alpha7 nicotinic receptors and tripled the expression of the antiapoptotic protein Bcl-2. These results strongly suggest that Galantamine can prevent apoptotic cell death by inducing neuroprotection through a mechanism related to that described for nicotine, i.e. activation of nAChRs and upregulation of Bcl-2. These findings might explain the long-term beneficial effects of Galantamine in patients suffering of Alzheimer's disease.
Silvia Lorrio - One of the best experts on this subject based on the ideXlab platform.
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effects of memantine and Galantamine given separately or in association on memory and hippocampal neuronal loss after transient global cerebral ischemia in gerbils
Brain Research, 2009Co-Authors: Silvia Lorrio, Pilar Negredo, J M Roda, Antonio G Garcia, Manuela G LopezAbstract:Abstract Galantamine is an acetylcholinesterase inhibitor and memantine is a non competitive antagonist of NMDA receptors that are being used to treat Alzheimer's disease (AD) patients. The fact that drugs with different mechanisms of action are available to treat AD introduces the prospect of prescribing drug combinations to amplify drug efficacy. This study was planed to evaluate the potential neuroprotective effects of Galantamine combined with memantine in a transient global cerebral ischemia model in gerbils. Animal groups included in the study were: sham, ischemia, and ischemia plus Galantamine (1 mg/kg and 10 mg/kg), memantine (10 mg/kg and 20 mg/kg), 1 mg/kg Galantamine plus 10 mg/kg memantine, and 10 mg/kg Galantamine plus 10 mg/kg memantine, respectively. Surviving pyramidal neurons in the CA1 subfield of the hippocampus, TUNEL, caspase-3 and SOD-2 immunohistochemistries, and the object placement test were evaluated 72 h after reperfusion. Memantine did not exert a clear neuroprotective effect, nor did it prevent spatial memory loss. In a previous study using the same experimental model, Galantamine was neuroprotective and improved spatial memory. In this study, the association of 10 mg/kg memantine with 10 mg/kg Galantamine increased the number of living pyramidal neurons, reduced TUNEL, active caspase-3 and SOD-2 immunoreactivity, and preserved spatial memory after ischemia-reperfusion injury; however, the effects of the combination were not statistically different from those observed in animals treated with Galantamine alone. We believe these results are of interest from a clinical point of view because the association of both drugs is being used in clinical practice and in clinical trials to treat Alzheimer's disease and vascular dementia.
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Galantamine postischemia provides neuroprotection and memory recovery against transient global cerebral ischemia in gerbils
Journal of Pharmacology and Experimental Therapeutics, 2007Co-Authors: Silvia Lorrio, J M Roda, Antonio G Garcia, Monica Sobrado, Esperanza Arias, Manuela G LopezAbstract:Galantamine, currently used in Alzheimer9s patients, has shown neuroprotection in hippocampal slices subjected to oxygenglucose deprivation. Here, we present an in vivo study to evaluate the potential neuroprotective effects of Galantamine in a transient global cerebral ischemia model in gerbils. Three treatment protocols were used. In the pretreatment protocol, gerbils were treated before ischemia and for 3 consecutive days thereafter. Eight groups of animals were included: sham operation plus placebo, 10 mg/kg mecamylamine and 10 mg/kg Galantamine, respectively; and ischemia plus placebo, 10 mg/kg mecamylamine, 1 mg/kg Galantamine, and 10 mg/kg Galantamine and 10 mg/kg mecamylamine plus Galantamine, respectively. Postischemia protocols included three groups of animals: sham operation, ischemia plus placebo, and ischemia plus 10 mg/kg Galantamine; substances were administered 3 or 6 h after ischemia and for 2 consecutive days thereafter. Pyramidal neurons surviving in the cornus ammonis 1 region of the hippocampus were evaluated 72 h after reperfusion, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) histochemistry, caspase-3 and superoxide dismutase (SOD)-2 immunohistochemistries, and Western blottings were performed, and object placement tests were carried out. Galantamine significantly increased the number of living pyramidal neurons after ischemia-reperfusion injury. Galantamine significantly reduced TUNEL, active caspase-3, and SOD-2 immunoreactivity. The nicotinic antagonist mecamylamine blocked the protective effects of Galantamine. The neuroprotective effects of Galantamine were preserved even when first administered at 3 h postischemia. These results correlated with the performance in the object placement test. This study shows that Galantamine provides in vivo neuroprotection and memory recovery against global cerebral ischemia, even when administration begins 3 h postischemia.
Jacqueline Birks - One of the best experts on this subject based on the ideXlab platform.
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The Cochrane Library - Galantamine for vascular cognitive impairment.
The Cochrane database of systematic reviews, 2006Co-Authors: Jacqueline Birks, David CraigAbstract:Background Vascular dementia represents the second most common type of dementia after that caused by Alzheimer's disease. Particularly in older patients, the combination of vascular dementia and Alzheimer's disease is common and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all patients fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss and the term vascular cognitive impairment is more useful. Currently, no established standard treatment for vascular cognitive impairment exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and vascular cognitive impairment raising the possibility that cholinesterase inhibitors such as Galantamine may be beneficial for the latter. Objectives To assess the efficacy of Galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or mixed dementia. Search methods The trials were identified from a search of ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 12 January 2013. The register contains information on trials identified from frequent searches of a number of major healthcare and medical databases (MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS) as well as from a number of international and national trial registries and grey literature sources. The terms used were: Galantamine, galanthamine, Reminyl, Razadyne, Nivalin. Selection criteria All unconfounded randomised double-blind trials comparing Galantamine with placebo were eligible for inclusion. Data collection and analysis Two review authors independently extracted the data from included studies. Main results Two trials, 1378 participants, employing randomised, double-blind, parallel-group methodology were included. Both trials were of six months duration and were testing a Galantamine dose of 16-24 mg/day in two divided doses. Both trials had an overall low risk of bias. The GAL-INT-6 trial included 592 patients with vascular dementia diagnosed according to recognised criteria and patients with Alzheimer's disease and coincidental radiographic findings of cerebrovascular disease. Limited outcome data were reported for the subgroup data with vascular dementia. In the whole trial population, statistically significant treatment effects in favour of Galantamine compared with placebo in cognition (ADAS-cog, mean difference (MD) -2.29, 95% confidence interval (CI) -3.46 to -1.12, P = 0.0001 ), activities of daily living (DAD, MD 4.10, 95% CI 1.25 to 6.95, P = 0.005) and behaviour (NPI, MD -2.06, 95% CI -4.09 to -0.03, P = 0.05 ) were noted. Significantly higher numbers of patients dropped out, (102/396 Galantamine, 33/196 placebo odds ratio (OR) 1.71, 95% CL 1.11 to 2.65, P = 0.02) and withdrew due to an adverse event from the group treated with Galantamine compared with the placebo group (79/396 Galantamine, 16/196 placebo, OR 2.80, 95% CI 1.59 to 4.95, P =0.0004). Data were also included from a second larger trial (GAL-INT-26) involving 788 patients with vascular dementia diagnosed using standard criteria. Statistically significant benefits favouring Galantamine over placebo in assessments of cognition (ADAS-cog, MD -1.50, 95% CI -2.39 to -0.61, P = 0.0009), and favouring placebo compared with Galantamine for behaviour (NPI, MD 1.80, 95% CI 0.29 to 3.31, P = 0.02) are recorded. Significantly higher numbers of patients dropped out from the group treated with Galantamine compared with the placebo group (50/396 Galantamine, 25/390 placebo OR 2.11, 95% CL 1.28 to 3.49, P = 0.004). Authors' conclusions Limited data were available when considering the impact of Galantamine on vascular dementia or vascular cognitive impairment. The data available suggest some advantage over placebo in the areas of cognition and global clinical state. In both included trials Galantamine produced higher rates of gastrointestinal side-effects. More studies are needed before firm conclusions can be drawn.
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Galantamine for vascular cognitive impairment
Cochrane Database of Systematic Reviews, 2006Co-Authors: Jacqueline Birks, David CraigAbstract:Background Vascular dementia represents the second most common type of dementia after that caused by Alzheimer's disease. Particularly in older patients, the combination of vascular dementia and Alzheimer's disease is common and is referred to as mixed dementia. The classification of vascular dementia broadly follows three clinico-pathological processes: multi-infarct dementia, single strategic infarct dementia and subcortical dementia. Not all patients fulfil strict criteria for dementia and may be significantly cognitively impaired without memory loss and the term vascular cognitive impairment is more useful. Currently, no established standard treatment for vascular cognitive impairment exists. Reductions in acetylcholine and acetyltransferase activity are common to both Alzheimer's disease and vascular cognitive impairment raising the possibility that cholinesterase inhibitors such as Galantamine may be beneficial for the latter. Objectives To assess the efficacy of Galantamine in the treatment of people with vascular cognitive impairment or vascular dementia or mixed dementia. Search methods The trials were identified from a search of ALOIS: the Cochrane Dementia and Cognitive Improvement Group’s Specialized Register on 12 January 2013. The register contains information on trials identified from frequent searches of a number of major healthcare and medical databases (MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS) as well as from a number of international and national trial registries and grey literature sources. The terms used were: Galantamine, galanthamine, Reminyl, Razadyne, Nivalin. Selection criteria All unconfounded randomised double-blind trials comparing Galantamine with placebo were eligible for inclusion. Data collection and analysis Two review authors independently extracted the data from included studies. Main results Two trials, 1378 participants, employing randomised, double-blind, parallel-group methodology were included. Both trials were of six months duration and were testing a Galantamine dose of 16-24 mg/day in two divided doses. Both trials had an overall low risk of bias. The GAL-INT-6 trial included 592 patients with vascular dementia diagnosed according to recognised criteria and patients with Alzheimer's disease and coincidental radiographic findings of cerebrovascular disease. Limited outcome data were reported for the subgroup data with vascular dementia. In the whole trial population, statistically significant treatment effects in favour of Galantamine compared with placebo in cognition (ADAS-cog, mean difference (MD) -2.29, 95% confidence interval (CI) -3.46 to -1.12, P = 0.0001 ), activities of daily living (DAD, MD 4.10, 95% CI 1.25 to 6.95, P = 0.005) and behaviour (NPI, MD -2.06, 95% CI -4.09 to -0.03, P = 0.05 ) were noted. Significantly higher numbers of patients dropped out, (102/396 Galantamine, 33/196 placebo odds ratio (OR) 1.71, 95% CL 1.11 to 2.65, P = 0.02) and withdrew due to an adverse event from the group treated with Galantamine compared with the placebo group (79/396 Galantamine, 16/196 placebo, OR 2.80, 95% CI 1.59 to 4.95, P =0.0004). Data were also included from a second larger trial (GAL-INT-26) involving 788 patients with vascular dementia diagnosed using standard criteria. Statistically significant benefits favouring Galantamine over placebo in assessments of cognition (ADAS-cog, MD -1.50, 95% CI -2.39 to -0.61, P = 0.0009), and favouring placebo compared with Galantamine for behaviour (NPI, MD 1.80, 95% CI 0.29 to 3.31, P = 0.02) are recorded. Significantly higher numbers of patients dropped out from the group treated with Galantamine compared with the placebo group (50/396 Galantamine, 25/390 placebo OR 2.11, 95% CL 1.28 to 3.49, P = 0.004). Authors' conclusions Limited data were available when considering the impact of Galantamine on vascular dementia or vascular cognitive impairment. The data available suggest some advantage over placebo in the areas of cognition and global clinical state. In both included trials Galantamine produced higher rates of gastrointestinal side-effects. More studies are needed before firm conclusions can be drawn.
