Memantine Acts as a Cholinergic Stimulant in the Mouse Hippocampus

摘要: The non-competitive NMDA receptor antagonist memantine, currently prescribed for the treatment of Alzheimer's disease, is assumed to prevent excitotoxicity implicated in neurodegenerative processes. Here, we investigated actions memantine on hippocampal function and signalling. In behavioural experiments using water maze, observed that (at 2 mg/kg) reversed scopolamine-induced learning deficits mice. When acutely applied mouse slices, caused a significant upward shift population spike input-output relationship at 10 100 microM, corresponding downward latency, indicative overall enhanced synaptic transmission. This action was blocked by muscarinic scopolamine (10 microM) but not MK-801 or GABA bicuculline (20 microM). Further, occluded potentiation induced 50 nM carbachol (CCh), while enhancing inhibitory CCh 1 suggesting additive actions. As anticipated an antagonist, microM (but also inhibited tetanus-induced long-term (LTP), NMDA-induced Ca;{2+} signals were cultured neurones (by 88%). Overall, our data suggest beyond antagonism, including stimulating effects cholinergic signalling via receptors. These interactions with system are likely contribute memantine's therapeutic potential.