Memantine, an N-methyl-D-aspartate receptor antagonist, is approved in the United States and Europe for the treatment of moderate to severe Alzheimer disease (AD) and has also been investigated in patients with mild to moderate AD. To characterize the specific cognitive benefits of memantine in patients with mild to moderate AD, a post hoc analysis was conducted of a 24-week randomized, double-blind, placebo-controlled, clinical trial comparing memantine (10 mg twice daily) to placebo. Cognition was assessed using the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total score, individual items, and aggregated subscales, using a mixed model repeated measures analysis. As assessed by the ADAS-cog total score, participants in the placebo group demonstrated significantly more cognitive decline from baseline than participants treated with memantine at all visits beginning at week 8. Subjects treated with placebo also declined significantly more than individuals in the memantine group on 5 of 11 ADAS-cog individual items: orientation, language, comprehension, word finding, and recall of test instructions. Out of 3 ADAS-cog aggregated item subscales (language, memory, and praxis), outcomes in 2 (language and memory) favored memantine. Consistent with findings from trials conducted in moderate to severe AD patients, this post hoc analysis of a randomized clinical trial suggests that memantine benefits core aspects of language and some aspects of memory in patients with mild to moderate AD.
"Because of its low-to moderate-affinity as a non-competitive antagonist of NMDA receptors (Szegedi et al., 2010), memantine appears all the more attractive in preventing excessive NMDA receptor activity without blocking synaptic transmission (Chen et al., 1998). Relative to placebo, memantine improved cognitive performances in patients with Alzheimer's disease (Bakchine and Loft, 2008; Ferris et al., 2009; Mecocci et al., 2009; Peskind et al., 2006; Pomara et al., 2007) and dementia with Lewy bodies (Emre et al., 2010), as well as activities of daily living in the former (Feldman et al., 2006). In addition, memantine is effective in treating neuropsychiatric symptoms of patients with Alzheimer and other dementias (Ballard and Corbett, 2010; Cummings et al., 2008; Maidment et al., 2008). "
[Show abstract][Hide abstract] ABSTRACT: Glutamate neurotoxicity has been proposed to be involved in Alzheimer pathogenesis, with clinical data supporting successful treatment with the NMDA receptor antagonist memantine. In the present study, the effects of subchronic memantine administration were assessed on spatial and non-spatial learning as well as exploratory activity and nest-building in APP/PS1 mutant mice. Memantine (10 mg/kg, i.p.) was better than placebo during the reversal phase of left-right discrimination, though equivalent to saline for Morris water maze and passive avoidance learning. The drug had no effect on non-learned behaviors in elevated plus-maze exploration and nest-building. These results support a specific action of the NMDA receptor antagonist on behavioral flexibility in mutant mice with amyloid pathology.
"Specifically, it has been shown that acetylsalicylic acid activates cochlear NMDA receptors29 and that the use of NMDA-antagonists at the round window abolishes tinnitus,29 while NMDA receptor agonists may induce tinnitus-like behaviors.30 Memantine, used to treat neuropathic pain and mild to moderate forms of Alzheimer’s disease,31 blocks NMDA transmission in hair cells (the same as salicylate acts upon)32 also modulating the cholinergic transmission. Acamprosate, a drug acting as both a NDMA-blocker and GABA-enhancer is used for alcohol withdrawal maintenance,33 recently proposed as an (augmentation) strategy to improve cognitive depressive symptoms,34 has recently been trialed for the management tinnitus with some success.35 "
[Show abstract][Hide abstract] ABSTRACT: Subjective tinnitus is a frequent, impairing condition, which may also cause neurotransmitter imbalance at the cochlea. Psychopharmacologic agents, although not being the first-line treatment for tinnitus, may modulate cochlear neurotransmission, thereby influencing the subjective tinnitus experience.
A comprehensive review of MEDLINE literature (from January 1990-January 2010) was performed searching for: "tinnitus", major classes of psychopharmacological agents, and psychiatric disorders. The most relevant clinical evidence is reported briefly along with a concise description of the main neurotransmitters purported to be involved in tinnitus, in order to provide the reader with a rational evaluation of tinnitus therapy with psychopharmacological agents.
Although strong methodological issues limit the reliability of the current results, a broad number of psychopharmacological agents have already been considered for tinnitus, both as candidate triggers or potential therapies.
Selected psychopharmacological drugs may play a role in the clinical management of this disorder. While the rational use of these agents for the treatment of tinnitus should not be overlooked, research should be undertaken on their neuromodulating actions at the cochlea.
[Show abstract][Hide abstract] ABSTRACT: A new analytic approach for modeling nonlinear RF circuits/subsystems, under multitone excitation is proposed. Particularly, the intermodulation (IM) distortion of fifth-order memoryless nonlinear systems is predicted under a randomly phase-modulated multitone excitation. The efficiency of the proposed approach is demonstrated by analyzing standard IM figures of merit such as MIMR and ACPR of a commercial RF power amplifier for different values of input power and number of input tones. The obtained results were compared to thirdorder models and have shown that restricting the analysis of highly nonlinear systems to third-order nonlinearity leads to optimistic results.
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