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Psychosocial Aspects of Diabetes
Published in Jahangir Moini, Matthew Adams, Anthony LoGalbo, Complications of Diabetes Mellitus, 2022
Jahangir Moini, Matthew Adams, Anthony LoGalbo
Memantine is the only example of N-methyl-D-aspartate receptor modulators that is currently used. It works by blocking the effects of glutamate in the brain, which causes large amounts of calcium to move into the neurons, causing their death. Memantine, therefore, is useful because it reduces the effects of glutamate, but does not totally block its binding. The adverse effects of memantine are headache, confusion, dizziness, and constipation. Because the two classes of AD medications work in different ways, they can be used in combination.
Fibromyalgia
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Memantine, a NMDAR antagonist typically used to treat dementia in Alzheimer’s disease, was studied in 63 patients with fibromyalgia in a double-blind, parallel randomized placebo controlled trial.148 Memantine was dosed at 20 mg/day after a 1-month titration period, and assessments of pain, global function, clinical impression, depression, anxiety, and quality of life were completed at baseline, post-treatment, and at 3- and 6-month follow-up. Memantine significantly reduced pain and increased pain threshold, and improved all other secondary outcomes with the exception of anxiety at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval = 2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval = 3 to 47). Memantine was well-tolerated, with dizziness (eight patients) and headache (four patients) the most common side effects.
Plant Alkaloids and Their Derivatives Relevant to Alzheimer’s Disease
Published in Atanu Bhattacharjee, Akula Ramakrishna, Magisetty Obulesu, Phytomedicine and Alzheimer’s Disease, 2020
Atanu Bhattacharjee, Akula Ramakrishna
The second class of FDA-approved medications acts by blocking NMDAR (Tariot et al., 2004). In AD, excess glutamate released from damaged cells causes a massive influx of calcium into neurons via NMDAR activation; this results in excitotoxicity, ultimately leading to neuronal death (Salloway et al., 2008). Memantine (Namenda™), a neuroprotective agent that blocks NMDAR, was approved for the treatment of moderate to severe AD in 2003. Memantine can be used alone or in combination with AChE inhibitors, such as donepezil (Szwajgier et al., 2013). Furthermore, antioxidants and free radical scavengers act as natural protectors to reduce the level of free radical accumulation and thereby slow down Aβ aggregation (Sarna et al., 2010; Hyun et al., 2009). Probable mechanisms of plant-derived alkaloids against AD progression are shown in Figure 17.1. A summary of current treatment strategies for AD is described in Table 17.1.
Extemporaneous combination of donepezil and memantine to treat dementia in Alzheimer disease: evidence from Italian real-world data
Published in Current Medical Research and Opinion, 2023
Alessandro Padovani, Serena Falato, Valeria Pegoraro
Adherence to therapy is the extent to which patients follow their medication schedules as prescribed by their doctors46. Treatment adherence was evaluated in terms of proportion of days covered (PDC), which corresponds to the total days of supply of medication dispensed over the length of the corresponding follow-up (i.e. 180 days). The PDC metric has been advocated by the Pharmacy Quality Alliance as the preferred indicator for estimating adherence to therapies for chronic diseases47 and it is known to provide a more conservative estimate of medication adherence compared to other measures in cases of concomitant multiple medications usage48. The number of days supplied by each prescription was calculated by dividing the total amount of active drug in each prescription by the corresponding daily maintenance dose (DMD). The maximum daily dosage for memantine is 20 mg. Patients shall assume 5 mg, 10 mg, and 15 mg of memantine once daily during the first, second, and third week of treatment respectively; starting from the fourth week of treatment, patients shall assume 20 mg of memantine once daily49; a dosage of 20 mg was considered as the DMD for memantine. The maximum daily dosage for donepezil is 10 mg. Patients shall assume 5 mg of donepezil once daily for at least the first month of treatment, then the doctor can decide to increase the daily dosage to 10 mg50; a dosage of 10 mg was considered as the DMD for donepezil. Days of supply contributed to the numerator only when memantine and donepezil overlapped.
Where do we go next in antidepressant drug discovery? A new generation of antidepressants: a pivotal role of AMPA receptor potentiation and mGlu2/3 receptor antagonism
Published in Expert Opinion on Drug Discovery, 2022
Andrzej Pilc, Agata Machaczka, Paweł Kawalec, Jodi L. Smith, Jeffrey M. Witkin
Ketamine has a rich pharmacology that also involves non-NMDA receptor targets and ketamine metabolites with a host of activities [29]. Based upon multiple pieces of data, some investigators have suggested that ketamine produces its antidepressant effects by way of non-NMDA receptor mechanisms [29,51]. For example, the ketamine metabolite, (2 R,6 R)-hydroxynorketamine (2 R,6 R-HNK), has shown antidepressant-like activity in animal models without having significant NMDA receptor affinity [52]. Likewise, opioid receptors have been implicated in the antidepressant effects of ketamine – naltrexone reduced the antidepressant response to ketamine but did not affect its dissociative properties in depressed patients – bipolar II or unipolar depression [53]. One of the biggest arguments against the NMDA receptor hypothesis comes from the lack of reported antidepressant efficacy of memantine (Namenda®) [54]. This might be due to the relatively few studies conducted and the potential lack of sufficient doses of memantine studied. However, recent meta-analyses documented overall efficacy of the low-affinity NMDA receptor antagonist memantine [55].
Cortical projection neurons as a therapeutic target in multiple sclerosis
Published in Expert Opinion on Therapeutic Targets, 2020
Tatjana Beutel, Julia Dzimiera, Hannah Kapell, Maren Engelhardt, Achim Gass, Lucas Schirmer
Another approach in the protection of excitatory neurons could be by pharmacological modulation of glutamate receptors at the postsynaptic membrane. Memantine, which is used in the treatment of Alzheimer’s disease, suppressed severity and duration of EAE [145]. Unfortunately, clinical trials with MS patients diagnosed with cognitive dysfunction treated with memantine had no benefit compared to those in the placebo group [146,147]. This data suggests that neuronal loss was already too substantial and could not be rescued by glutamate modulation or that modulation of glutamate receptors needs to be more specific considering that there are allelic variants of NMDA receptors [148]. Another possibility of preventing excitotoxicity could be by activating genes expressing glutamate transporters in astrocytes. Beta-lactam antibiotics are known for acting as a transcriptional factor inducing glutamate transporter expression [149]. Animal studies have shown that the beta-lactam antibiotic ceftriaxone increased the expression of the glutamate transporter EAAT2/GLT-1 in astocytes, which led to a neuroprotective effect in an ALS mouse model [149].