The Experts below are selected from a list of 9582 Experts worldwide ranked by ideXlab platform
Akinori Akaike - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effects of galanthamine and tacrine against glutamate neurotoxicity
European Journal of Pharmacology, 2006Co-Authors: Yuki Takadatakatori, Toshiaki Kume, Mitsuhiro Sugimoto, Hiroshi Katsuki, Tetsuhiro Niidome, Hachiro Sugimoto, Takeshi Fujii, Susumu Okabe, Akinori AkaikeAbstract:We examined the mechanisms of the neuroprotective effects of two central-type Acetylcholinesterase Inhibitors, galanthamine and tacrine, on nitric oxide-mediated glutamate neurotoxicity using primary cultures from the cerebral cortex of fetal rats. Galanthamine and tacrine showed prominent protective effects against glutamate neurotoxicity. Mecamylamine, a nicotinic acetylcholine receptor antagonist, but not scopolamine, a muscarinic acetylcholine receptor antagonist, inhibited the protective effects of these Inhibitors on glutamate neurotoxicity. Furthermore, dihydro-β-erythroidine, an α4-nicotinic receptor antagonist, and methyllycaconitine, an α7-nicotinic receptor antagonist, inhibited the neuroprotective effects of galanthamine but not tacrine. Next, we investigated the site of action where galanthamine and tacrine prevent glutamate neurotoxicity. Both these Acetylcholinesterase Inhibitors prevented glutamate- and ionomycin-induced neurotoxicity, but only tacrine prevented S-nitrosocysteine-induced neurotoxicity. These results suggest that galanthamine and tacrine protect cortical neurons from glutamate neurotoxicity via different mechanisms.
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Acetylcholinesterase Inhibitors used in treatment of alzheimer s disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3 kinase cascade
Neuropharmacology, 2006Co-Authors: Yuki Takadatakatori, Toshiaki Kume, Mitsuhiro Sugimoto, Hiroshi Katsuki, Hachiro Sugimoto, Akinori AkaikeAbstract:Abstract We show here that donepezil, galanathamine and tacrine, therapeutic Acetylcholinesterase Inhibitors currently being used for treatment of Alzheimer's disease, protect neuronal cells in a time- and concentration-dependent manner from glutamate neurotoxicity that involves apoptosis. The neuroprotective effects were antagonized by mecamylamine, an inhibitor of nicotinic acetylcholine receptors (nAChRs). Dihydro-β-erythroidine and methyllycaconitine, antagonists for α4-nAChR and α7-nAChR, respectively, antagonized the protective effect of donepezil and galanthamine, but not that of tacrine. Previous reports suggest the involvement of the phosphatidylinositol 3-kinase (PI3K)–Akt pathway in the nicotine-induced neuroprotection. Inhibitors for a non-receptor type tyrosine kinase, Fyn, and janus-activated kinase 2, suppressed the neuroprotective effect of donepezil and galanthamine, but not that of tacrine. Furthermore, LY294002, a PI3K inhibitor, also suppressed the neuroprotective effect of donepezil and galanthamine, but not that of tacrine. The phosphorylation of Akt, an effector of PI3K, and the expression level of Bcl-2, an anti-apoptotic protein, increased with donepezil and galanthamine treatment, but not with tacrine treatment. These results suggest that donepezil and galanthamine prevent glutamate neurotoxicity through α4- and α7-nAChRs, followed by the PI3K–Akt pathway, and that tacrine protects neuronal cells through a different pathway.
Vachiraporn Ajavakom - One of the best experts on this subject based on the ideXlab platform.
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Novel Racemic Tetrahydrocurcuminoid Dihydropyrimidinone Analogues as Potent Acetylcholinesterase Inhibitors.
ChemInform, 2013Co-Authors: Sarawalee Arunkhamkaew, Anan Athipornchai, Nuttapon Apiratikul, Apichart Suksamrarn, Vachiraporn AjavakomAbstract:A variety of the title pyrimidinone derivatives (IV) (12 examples) are synthesized utilizing a CuSO4-catalyzed multicomponent Biginelli reaction.
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Novel racemic tetrahydrocurcuminoid dihydropyrimidinone analogues as potent Acetylcholinesterase Inhibitors
Bioorganic & medicinal chemistry letters, 2013Co-Authors: Sarawalee Arunkhamkaew, Anan Athipornchai, Nuttapon Apiratikul, Apichart Suksamrarn, Vachiraporn AjavakomAbstract:Abstract The synthesis of racemic tetrahydrocurcumin- (THC-), tetrahydrodemethoxycurcumin- (THDC-) and tetrahydrobisdemethoxycurcumin- (THBDC-) dihydropyrimidinone (DHPM) analogues was achieved by utilizing the multi-component Biginelli reaction in the presence of copper sulphate as a catalyst. The evaluation of Acetylcholinesterase Inhibitors for Alzheimer’s disease of these compounds showed that they exhibited higher inhibitory activity than their parent analogues. THBDC–DHPM demonstrated the most potent inhibitory activity with an IC50 value of 1.34 ± 0.03 μM which was more active than the approved drug galanthamine (IC50 = 1.45 ± 0.04 μM).
Yuki Takadatakatori - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effects of galanthamine and tacrine against glutamate neurotoxicity
European Journal of Pharmacology, 2006Co-Authors: Yuki Takadatakatori, Toshiaki Kume, Mitsuhiro Sugimoto, Hiroshi Katsuki, Tetsuhiro Niidome, Hachiro Sugimoto, Takeshi Fujii, Susumu Okabe, Akinori AkaikeAbstract:We examined the mechanisms of the neuroprotective effects of two central-type Acetylcholinesterase Inhibitors, galanthamine and tacrine, on nitric oxide-mediated glutamate neurotoxicity using primary cultures from the cerebral cortex of fetal rats. Galanthamine and tacrine showed prominent protective effects against glutamate neurotoxicity. Mecamylamine, a nicotinic acetylcholine receptor antagonist, but not scopolamine, a muscarinic acetylcholine receptor antagonist, inhibited the protective effects of these Inhibitors on glutamate neurotoxicity. Furthermore, dihydro-β-erythroidine, an α4-nicotinic receptor antagonist, and methyllycaconitine, an α7-nicotinic receptor antagonist, inhibited the neuroprotective effects of galanthamine but not tacrine. Next, we investigated the site of action where galanthamine and tacrine prevent glutamate neurotoxicity. Both these Acetylcholinesterase Inhibitors prevented glutamate- and ionomycin-induced neurotoxicity, but only tacrine prevented S-nitrosocysteine-induced neurotoxicity. These results suggest that galanthamine and tacrine protect cortical neurons from glutamate neurotoxicity via different mechanisms.
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Acetylcholinesterase Inhibitors used in treatment of alzheimer s disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3 kinase cascade
Neuropharmacology, 2006Co-Authors: Yuki Takadatakatori, Toshiaki Kume, Mitsuhiro Sugimoto, Hiroshi Katsuki, Hachiro Sugimoto, Akinori AkaikeAbstract:Abstract We show here that donepezil, galanathamine and tacrine, therapeutic Acetylcholinesterase Inhibitors currently being used for treatment of Alzheimer's disease, protect neuronal cells in a time- and concentration-dependent manner from glutamate neurotoxicity that involves apoptosis. The neuroprotective effects were antagonized by mecamylamine, an inhibitor of nicotinic acetylcholine receptors (nAChRs). Dihydro-β-erythroidine and methyllycaconitine, antagonists for α4-nAChR and α7-nAChR, respectively, antagonized the protective effect of donepezil and galanthamine, but not that of tacrine. Previous reports suggest the involvement of the phosphatidylinositol 3-kinase (PI3K)–Akt pathway in the nicotine-induced neuroprotection. Inhibitors for a non-receptor type tyrosine kinase, Fyn, and janus-activated kinase 2, suppressed the neuroprotective effect of donepezil and galanthamine, but not that of tacrine. Furthermore, LY294002, a PI3K inhibitor, also suppressed the neuroprotective effect of donepezil and galanthamine, but not that of tacrine. The phosphorylation of Akt, an effector of PI3K, and the expression level of Bcl-2, an anti-apoptotic protein, increased with donepezil and galanthamine treatment, but not with tacrine treatment. These results suggest that donepezil and galanthamine prevent glutamate neurotoxicity through α4- and α7-nAChRs, followed by the PI3K–Akt pathway, and that tacrine protects neuronal cells through a different pathway.
Hachiro Sugimoto - One of the best experts on this subject based on the ideXlab platform.
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neuroprotective effects of galanthamine and tacrine against glutamate neurotoxicity
European Journal of Pharmacology, 2006Co-Authors: Yuki Takadatakatori, Toshiaki Kume, Mitsuhiro Sugimoto, Hiroshi Katsuki, Tetsuhiro Niidome, Hachiro Sugimoto, Takeshi Fujii, Susumu Okabe, Akinori AkaikeAbstract:We examined the mechanisms of the neuroprotective effects of two central-type Acetylcholinesterase Inhibitors, galanthamine and tacrine, on nitric oxide-mediated glutamate neurotoxicity using primary cultures from the cerebral cortex of fetal rats. Galanthamine and tacrine showed prominent protective effects against glutamate neurotoxicity. Mecamylamine, a nicotinic acetylcholine receptor antagonist, but not scopolamine, a muscarinic acetylcholine receptor antagonist, inhibited the protective effects of these Inhibitors on glutamate neurotoxicity. Furthermore, dihydro-β-erythroidine, an α4-nicotinic receptor antagonist, and methyllycaconitine, an α7-nicotinic receptor antagonist, inhibited the neuroprotective effects of galanthamine but not tacrine. Next, we investigated the site of action where galanthamine and tacrine prevent glutamate neurotoxicity. Both these Acetylcholinesterase Inhibitors prevented glutamate- and ionomycin-induced neurotoxicity, but only tacrine prevented S-nitrosocysteine-induced neurotoxicity. These results suggest that galanthamine and tacrine protect cortical neurons from glutamate neurotoxicity via different mechanisms.
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Acetylcholinesterase Inhibitors used in treatment of alzheimer s disease prevent glutamate neurotoxicity via nicotinic acetylcholine receptors and phosphatidylinositol 3 kinase cascade
Neuropharmacology, 2006Co-Authors: Yuki Takadatakatori, Toshiaki Kume, Mitsuhiro Sugimoto, Hiroshi Katsuki, Hachiro Sugimoto, Akinori AkaikeAbstract:Abstract We show here that donepezil, galanathamine and tacrine, therapeutic Acetylcholinesterase Inhibitors currently being used for treatment of Alzheimer's disease, protect neuronal cells in a time- and concentration-dependent manner from glutamate neurotoxicity that involves apoptosis. The neuroprotective effects were antagonized by mecamylamine, an inhibitor of nicotinic acetylcholine receptors (nAChRs). Dihydro-β-erythroidine and methyllycaconitine, antagonists for α4-nAChR and α7-nAChR, respectively, antagonized the protective effect of donepezil and galanthamine, but not that of tacrine. Previous reports suggest the involvement of the phosphatidylinositol 3-kinase (PI3K)–Akt pathway in the nicotine-induced neuroprotection. Inhibitors for a non-receptor type tyrosine kinase, Fyn, and janus-activated kinase 2, suppressed the neuroprotective effect of donepezil and galanthamine, but not that of tacrine. Furthermore, LY294002, a PI3K inhibitor, also suppressed the neuroprotective effect of donepezil and galanthamine, but not that of tacrine. The phosphorylation of Akt, an effector of PI3K, and the expression level of Bcl-2, an anti-apoptotic protein, increased with donepezil and galanthamine treatment, but not with tacrine treatment. These results suggest that donepezil and galanthamine prevent glutamate neurotoxicity through α4- and α7-nAChRs, followed by the PI3K–Akt pathway, and that tacrine protects neuronal cells through a different pathway.
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donepezil hydrochloride e2020 and other Acetylcholinesterase Inhibitors
Current Medicinal Chemistry, 2000Co-Authors: Hachiro Sugimoto, Yoshiharu Yamanishi, Youichi Iimura, Yoshiyuki KawakamiAbstract:A wide range of evidence shows that Acetylcholinesterase (AChE) Inhibitors can interfere with the progression of Alzheimer's disease (AD). The successful development of these compounds was based on a well-accepted theory that the decline in cognitive and mental functions associated with AD is related to the loss of cortical cholinergic neurotransmission. The earliest known AChE Inhibitors, namely, physostigmine and tacrine, showed modest improvement in the cognitive function of Alzheimer's patients. However, clinical studies show that physostigmine has poor oral activity, brain penetration and pharmacokinetic parameters while tacrine has hepatotoxic liability. Studies were then focused on finding a new type of Acetylcholinesterase inhibitor that would overcome the disadvantages of these two compounds. Donepezil hydrochloride inaugurates a new class of AChE Inhibitors with longer and more selective action with manageable adverse effects. Currently, there are about 19 new Alzheimer's drugs in various phases of clinical development.
Pablo R Duchowicz - One of the best experts on this subject based on the ideXlab platform.
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qsar analysis on tacrine related Acetylcholinesterase Inhibitors
Journal of Biomedical Science, 2014Co-Authors: Kai Y Wong, Andrew G Mercader, Laura Saavedra, Bahareh Honarparvar, Gustavo P Romanelli, Pablo R DuchowiczAbstract:The evaluation of the clinical effects of Tacrine has shown efficacy in delaying the deterioration of the symptoms of Alzheimer's disease, while confirming the adverse events consisting mainly in the elevated liver transaminase levels. The study of tacrine analogs presents a continuous interest, and for this reason we establish Quantitative Structure-Activity Relationships on their Acetylcholinesterase inhibitory activity. Ten groups of new developed Tacrine-related Inhibitors are explored, which have been experimentally measured in different biochemical conditions and AChE sources. The number of included descriptors in the structure-activity relationship is characterized by `Rule of Thumb'. The 1502 applied molecular descriptors could provide the best linear models for the selected Alzheimer's data base and the best QSAR model is reported for the considered data sets. The QSAR models developed in this work have a satisfactory predictive ability, and are obtained by selecting the most representative molecular descriptors of the chemical structure, represented through more than a thousand of constitutional, topological, geometrical, quantum-mechanical and electronic descriptor types.
