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Updated: Jul 10, 2026
07:56
A Plate-Based Assay for the Measurement of Endogenous Monoamine Release in Acute Brain Slices
Published on: August 11, 2021
Memantine agonist action at dopamine D2High receptors
Philip Seeman1, Carla Caruso, Mercedes Lasaga
1Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8. philip.seeman@utoronto.ca
Synapse (New York, N.Y.)
|November 15, 2007
Summary
Memantine, used for Alzheimer's and Parkinson's disease, may trigger psychosis due to its action on dopamine D2(High) receptors and N-methyl-D-aspartate (NMDA) receptors.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Memantine improves Alzheimer's and Parkinson's disease symptoms.
- Memantine can induce psychosis in Parkinson's patients, suggesting a dopamine link.
Purpose of the Study:
- To investigate memantine's potency at dopamine D2(High) receptors.
- To compare memantine's affinity for D2(High) and N-methyl-D-aspartate (NMDA) receptors.
Main Methods:
- Radioligand binding assays using [(3)H]domperidone and [(3)H]MK 801.
- Guanosine triphosphate (GTP) binding assays in D2-expressing cells.
- Inhibition of prolactin release from pituitary cells.
Main Results:
- Memantine's dissociation constant at rat D2(High) was 917 nM and at human D2Long was 137 nM.
- Memantine's dissociation constant at NMDA receptors was 2200 nM.
- Memantine (200-2000 nM) inhibited prolactin release, indicating D2(High) receptor interaction.
Conclusions:
- Memantine acts on both dopamine D2(High) and NMDA receptors.
- The dual action of memantine likely explains its clinical effects, including psychosis in Parkinson's patients.
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