Reduction of cerebrospinal fluid amyloid beta after systemic administration of M1 muscarinic agonists

Brain Res. 2001 Jun 29;905(1-2):220-3. doi: 10.1016/s0006-8993(01)02484-2.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Amyloid beta-Protein Precursor / cerebrospinal fluid
  • Amyloid beta-Protein Precursor / drug effects*
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cerebrospinal Fluid / drug effects*
  • Cerebrospinal Fluid / metabolism
  • Female
  • Muscarinic Agonists / pharmacology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Peptide Fragments / cerebrospinal fluid
  • Piperidines / pharmacology
  • Quinuclidines / pharmacology
  • Rabbits
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • Thiazoles / pharmacology
  • Thiophenes*

Substances

  • 1-methylpiperidine-4-spiro-(2'-methylthiazoline)
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Muscarinic Agonists
  • Peptide Fragments
  • Piperidines
  • Quinuclidines
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic
  • Thiazoles
  • Thiophenes
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • cevimeline