Reduction of cerebrospinal fluid amyloid beta after systemic administration of M1 muscarinic agonists.
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.
Beach
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Sun Health Research Institute, 10515 Santa Fe Drive, Sun City, AZ 85372, USA. thomas.beach@mail.sunhealth.org
Walker
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Potter
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Sue
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Fisher
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A
D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid / Q000187:drug effects*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D011817:Rabbits; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D013876:Thiophenes
C111926:1-methylpiperidine-4-spiro-(2'-methylthiazoline); D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018721:Muscarinic Agonists; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; D013844:Thiazoles; D013876:Thiophenes; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C059240:cevimeline