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Updated: Aug 23, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
07:02

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development

Published on: February 11, 2019

Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil

Antonia P Periclou1, Daniel Ventura, Tyler Sherman

  • 1Clinical Pharmacology and Drug Dynamics, Forest Research Institute, Jersey City, NJ 07311-4994, USA. Antonia.Periclou@frx.com

The Annals of Pharmacotherapy
|July 22, 2004
PubMed
Abstract

Insights

This study found no significant pharmacokinetic interactions between memantine and donepezil. These Alzheimer's disease medications can likely be safely combined for patient benefit.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Clinical Pharmacology

Background:

  • Memantine is an NMDA receptor antagonist approved for moderate to severe Alzheimer's disease.
  • Donepezil is an acetylcholinesterase (AChE) inhibitor used for Alzheimer's treatment.

Purpose of the Study:

  • To investigate potential pharmacokinetic interactions between memantine and donepezil.
  • To assess the safety and tolerability of combined memantine and donepezil administration.

Main Methods:

  • Open-label study in 24 healthy subjects (18-35 years).
  • Administered memantine and donepezil separately and concomitantly.
  • Monitored pharmacokinetic parameters and AChE inhibition in red blood cells.

Main Results:

  • No significant pharmacokinetic interactions observed between memantine and donepezil.
  • AChE inhibition by donepezil was not significantly altered by co-administered memantine.
  • Combined administration was well tolerated, with adverse events primarily associated with donepezil alone.

Conclusions:

  • Memantine and donepezil do not exhibit significant pharmacokinetic interactions.
  • Combination therapy with memantine and donepezil appears safe and effective for Alzheimer's disease management.

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