Interaction of Memantine with Cholecystokinin Receptors in Mouse Brain

— The effect of memantine on CCK receptors in mouse brain has been investigated using particles of dissected cortex and striatum. Total binding of radio-labelled CCK33 was one-half maximal within 10 min of incubation and reached a maximum after 30 to 60 min when either cortex or striatum was used. Non-specific binding (presence of 100 μM unlabelled CCK8) was 50 to 80% of total binding at steady state conditions. CCK8 inhibited specific binding of radiolabeled CCK33 in a dose-dependent manner; the IC50 (half-maximal inhibitory concentration) was in the range 3 to 4 nM. Memantine increased CCK binding in a concentration-dependent manner, though at high concentrations. The EC50 (half-maximal effective concentration) of this effect was < 100 μM. The memantine effect is not due to an inhibition of labelled CCK degradation in the medium. The effect of memantine on CCK binding is unique for brain since it was not observed in pancreatic acinar membranes. These data, therefore, suggest a modulatory effect of memantine on CCK receptors in mouse brain (cortex and striatum) particles.