Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease.
Current pharmacotherapy for Alzheimer's disease involves compounds that are aimed at increasing the levels of acetylcholine in the brain by facilitating cholinergic neurotransmission through inhibition of cholinesterase. These drugs, known as acetylcholinesterase inhibitors, have been shown to improve cognition and global functions but have little impact on improving the eventual progression of the disease; however, there is evidence that other cholinesterases such as butyrylcholinesterase can play an important role in cholinergic function in the brain, and the long-suspected non-cholinergic actions of acetylcholinesterase, mainly the interference with the beta-amyloid protein cascade, have recently driven a profound revolution in cholinesterase drug research. Several disease-modifying agents are under development that target these enzymes and have hope of becoming the next generation of effective drugs in the treatment of Alzheimer's disease.
Martinez
Ana
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NeuroPharma, Avda de la Industria 52, 28760 Madrid, Spain. amartinez@neuropharma.es
Castro
Ana
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D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000378:metabolism; D002219:Carbamates / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D005702:Galantamine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010830:Physostigmine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D011487:Protein Conformation / Q000187:drug effects
C487591:4-((1S)-methylamino-3-(4-nitrophenoxy))propylphenyl N,N-dimethylcarbamate; D016229:Amyloid beta-Peptides; D002219:Carbamates; D002800:Cholinesterase Inhibitors; D005702:Galantamine; D010830:Physostigmine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C092280:phenserine