Related Experiment Video
Updated: May 27, 2026
Using Enzyme-based Biosensors to Measure Tonic and Phasic Glutamate in Alzheimer's Mouse Models
Published on: May 3, 2017
Acute pharmacokinetics of memantine in the mouse
1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Molecular Genetics and Program in Neuroscience, University of Toronto, Toronto, Ont., Canada. saab @ hifo.uzh.ch
Abstract:
The pharmacokinetics of memantine, a widely prescribed medication in the United States and the European Union for the treatment of moderate-to-severe Alzheimer's disease (AD), have not been well explored in the mouse. Memantine is a highly unspecific blocker of many channels and how memantine may be of benefit in AD remains a mystery. Therefore, the investigation of memantine in the mouse, the most commonly chosen subject for modeling AD, has strong potential to lead to better therapies. Here, we present an acute pharmacokinetic analysis of memantine in mouse brain tissue and blood serum for a variety of experimentally relevant doses. The data help shed light on the mechanism of memantine action in vivo, and demonstrate that subcutaneous doses above 10 mg/kg in the mouse are most likely not therapeutically relevant to the human.
Insights
Memantine pharmacokinetics in mice were analyzed for Alzheimer's disease (AD) research. Doses above 10 mg/kg in mice are unlikely to be therapeutically relevant for humans.
Area of Science:
- Neuroscience
- Pharmacology
- Alzheimer's Disease Research
Background:
- Memantine is a common Alzheimer's disease (AD) treatment, but its mechanism and pharmacokinetics in mice are unclear.
- Mice are crucial models for AD research, necessitating understanding of drug behavior in this species.
- Memantine's broad channel-blocking activity complicates its therapeutic role in AD.
Purpose of the Study:
- To characterize the acute pharmacokinetics of memantine in mouse brain and serum.
- To determine experimentally relevant doses for memantine in mouse models of AD.
- To provide insights into memantine's in vivo mechanism of action.
Main Methods:
- Acute pharmacokinetic analysis of memantine.
- Measurement in mouse brain tissue and blood serum.
- Administration of various experimentally relevant doses.
Main Results:
- Established memantine concentration-time profiles in mouse brain and serum.
- Identified a dose-dependent relationship between administration and tissue/serum levels.
- Demonstrated that subcutaneous doses >10 mg/kg in mice are unlikely to be therapeutically relevant to humans.
Conclusions:
- The study provides essential pharmacokinetic data for memantine in mice.
- Findings suggest limitations for high-dose memantine use in mouse models for human AD therapy.
- Further research is needed to elucidate memantine's precise mechanism in AD.
