Abstract
Overproduction of the peptide amyloid beta (A beta) is a critical event in Alzheimer's disease (AD). Systemic administration of 3 M1-selective muscarinic agonists, AF102B, AF150S and AF267B, decreased cerebrospinal fluid (CSF) A beta concentrations; levels of CSF secreted beta-APP were not significantly altered. Rabbits treated for 5 days with s.c. injections of each drug (2 mg/kg/day) had levels of CSF A beta which were between 55 and 71% of control for A beta 1-40 and between 59 and 84% of control for A beta 1--42.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / cerebrospinal fluid*
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Alzheimer Disease / drug therapy
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / cerebrospinal fluid*
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Amyloid beta-Protein Precursor / cerebrospinal fluid
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Amyloid beta-Protein Precursor / drug effects*
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Animals
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Brain / drug effects
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Brain / metabolism
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Cerebrospinal Fluid / drug effects*
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Cerebrospinal Fluid / metabolism
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Female
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Muscarinic Agonists / pharmacology*
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Neurons / drug effects
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Neurons / metabolism
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Peptide Fragments / cerebrospinal fluid
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Piperidines / pharmacology
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Quinuclidines / pharmacology
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Rabbits
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Receptor, Muscarinic M1
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Receptors, Muscarinic / drug effects*
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Receptors, Muscarinic / metabolism
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Thiazoles / pharmacology
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Thiophenes*
Substances
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1-methylpiperidine-4-spiro-(2'-methylthiazoline)
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Muscarinic Agonists
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Peptide Fragments
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Piperidines
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Quinuclidines
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Receptor, Muscarinic M1
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Receptors, Muscarinic
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Thiazoles
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Thiophenes
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amyloid beta-protein (1-40)
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amyloid beta-protein (1-42)
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cevimeline