Muscarinic receptor function and acetylcholinesterase activity after chronic administration of tacrine to mice at therapeutic drug concentrations

Jennifer S. Kiefer-Day, Esam E. El-Fakahany

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

We administered 9-amino-1,2,3,4-tetrahydroacridine (THA, Tacrine™) to mice in doses (0.3-3 mg/kg) which have been shown to enhance cognition. Animals were sacrificed at various time points and several markers of cholinergic function were measured. Following 3 mg/kg THA, drug levels in brain were sufficient to inhibit 78-80% of brain acetylcholinesterase activity, regardless of treatment duration. However, repeated administration of THA did not alter the number of muscarinic receptors or the phosphoinositide response to muscarinic receptor agonists. Thus, at therapeutically relevant doses, THA inhibits the activity of brain acetylcholinesterase substantially, but does not affect the density of muscarinic receptors on their ability to activate second messenger systems. These results are in contrast to those obtained by other investigators who found significant decreases in muscarinic receptor number following chronic administration of higher doses of THA.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalPharmacology
Volume44
Issue number2
DOIs
StatePublished - Jan 1 1992

Keywords

  • Alzheimer’s disease
  • Cholinesterase inhibitor
  • Muscarinic receptor
  • THA (9-amino-1,2,3,4-tetrahydroacridine)
  • Tacrine<sup>™</sup>

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