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Antagonist Memantine (antagonist + memantine)
Selected AbstractsEffects of the Non-Competitive NMDA Receptor Antagonist Memantine on the Volitional Consumption of Ethanol by Alcohol-Preferring RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2010Gloria E. Malpass This study examined the effects of memantine, a low-affinity, open channel NMDA antagonist, on volitional consumption of ethanol by alcohol-preferring rats and potential locomotor, sedative and hypothermic effects. Volitional consumption of ethanol in a 24-hr two-choice paradigm was determined for male Myers' high-ethanol-preferring (mHEP) rats. Effects of memantine (0.3, 1.0, 3.0 and 10.0 mg/kg, i.p., b.i.d. [twice daily] for 3 days) or vehicle on volitional consumption of ethanol, proportion of ethanol to total fluids consumed, total fluid intake and consumption of food were observed. Potential sedating and locomotor effects of memantine (10.0 mg/kg, i.p., b.i.d.) were determined using an elevated plus maze and an Auto-Track Opto-Varimex activity monitoring system. Rectal temperature was measured to determine if memantine (10.0 mg/kg, i.p.) produces a hypothermic effect. The results indicate that memantine dose-dependently decreased the amount of ethanol and proportion of ethanol to total fluids consumed daily, reaching 48% and 24%, respectively, at the highest dose. These effects did not appear to be anti-caloric. Memantine (10.0 mg/kg) partially reversed both the sedation and the reductions in locomotor activity induced by ethanol. This dose did, however, produce a small, partially reversible hypothermic effect. In conclusion, memantine may decrease ethanol consumption with fewer side effects than other NMDA receptor antagonists, such as phencyclidine (PCP), MK 801 and ketamine. [source] Reducing conditions significantly attenuate the neuroprotective efficacy of competitive, but not other NMDA receptor antagonists in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2000Ashley K. Pringle Abstract Inappropriate activation of NMDA receptors during a period of cerebral ischaemia is a crucial event in the pathway leading to neuronal degeneration. However, significant research has failed to deliver a clinically active NMDA receptor antagonist, and competitive NMDA antagonists are ineffective in many experimental models of ischaemia. The NMDA receptor itself has a number of modulatory sites which may affect receptor function under ischaemic conditions. Using rat organotypic hippocampal slice cultures we have investigated whether the redox modulatory site affects the neuroprotective efficacy of NMDA receptor antagonists against excitotoxicity and experimental ischaemia (OGD). NMDA toxicity was significantly enhanced in cultures pretreated with a reducing agent. The noncompetitive antagonist MK-801 and a glycine-site blocker were equally neuroprotective in both normal and reduced conditions, but there was a significant rightward shift in the dose,response curves of the competitive antagonists APV and CPP and the uncompetitive antagonist memantine. OGD produced neuronal damage predominantly in the CA1 region, which was prevented by MK-801 and memantine, but not by APV or CPP. Inclusion of an oxidizing agent during the period of OGD had no effect alone, but significantly enhanced the neuroprotective potency of the competitive antagonists. These data clearly demonstrate that chemical reduction of the redox modulatory site of the NMDA receptor decreases the ability of competitive antagonists to block NMDA receptor-mediated neuronal damage, and that the reducing conditions which occur during simulated ischaemia are sufficient to produce a similar effect. This may have important implications for the design of future neuroprotective agents. [source] The effects of the glutamate antagonist memantine on brain activation to an auditory perception taskHUMAN BRAIN MAPPING, Issue 11 2009Heidi van Wageningen Abstract Glutamate is critically involved in the regulation of cognitive functions in humans. There is, however, sparse evidence regarding how blocking glutamate action at the receptor site during a cognitive task affects brain activation. In the current study, the effects of the glutamate antagonist memantine were examined with functional magnetic resonance imaging (fMRI). Thirty-one healthy adults were scanned twice in a counter-balanced design, either in a no-drug session or after administration of memantine for 21 days. The subjects performed a simple auditory perception task with consonant-vowel stimuli. Group-level spatial independent component analysis (ICA) was used to decompose the data and to extract task-related activations. The focus was on four task-related ICA components with frontotemporal localization. The results showed that glutamate-blockage resulted in a significant enhancement in one component, with no significant effect in the other three components. The enhanced effect of memantine was in the middle temporal gyrus, superior frontal gyrus, and middle frontal gyrus. It is suggested that the results reflect effects of glutamatergic processes primarily through non- N -methyl- D -aspartate (NMDA) receptor pathways. Moreover, the results demonstrate that memantine can be used as a probe which allows for studying the effect of excitatory neurotransmission on neuronal activation. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] NMDA antagonist memantine improves levodopa-induced dyskinesias and "On-off" phenomena in Parkinson's disease,MOVEMENT DISORDERS, Issue 4 2010Sara Varanese MD No abstract is available for this article. [source] The Treatment of Cognitive Impairment Associated with Parkinson's DiseaseBRAIN PATHOLOGY, Issue 3 2010David J. Burn FRCP Abstract Cognitive impairment and dementia associated with Parkinson's disease (PD) are common and often have devastating effects upon the patient and their family. Early cognitive impairment in PD is frequent, and the functional impact may be underestimated. Optimal management will rely upon better identification of the predominant symptoms and greater knowledge of their pathophysiological basis. The management of dementia in PD (PD-D) also has to consider the significant neuropsychiatric burden that frequently accompanies the cognitive decline, as well as fluctuations in attention. Atypical anti-psychotics have a limited role at present in treating PD-D, although new drugs are under development. The mainstay of drug management for people with PD-D is cholinesterase inhibitors, although recent trials have suggested that the N-methyl-D aspartate antagonist memantine may also have some benefit. Disease modification remains the ultimate goal for preventing the inexorable decline in PD-D, although effective interventions are still some way off. Limited benefit may, however, be possible through exercise programmes and so-called "medical foods", although randomised trials are required to confirm largely anecdotal observations. [source] | |||||||||||||