Memantine represents a new class of effective therapeutic agents for the symptomatic treatment of moderately severe to severe Alzheimer's disease (AD) with moderate affinity, N-methyl-D- non-competitive aspartate (NMDA) receptor antagonist with strong voltage dependence and fast kinetics. Treatment with a high therapeutic dose of memantine 10 mg/kg obviously reduced cisplatin-induced neurobehavioral toxicity. Memantine blocks the NMDA receptor pore; the mechanisms through which NMDA antagonists might be useful for neurobehavioral protection [19]. One of the serious side effects of the anticancer drug cisplatin is its neurotoxicity, which can be caused by activation of the extracellular pathway of apoptosis in cells. Since memantine, a clinically used N-methyl-D-aspartic acid (NMDA) receptor antagonist, shows antiapoptotic action in several models of neuronal cell damage, in this study we evaluated the effect of memantine on the effect neurobehavioral effects induced by cisplatin in mice. 20]. In a well-described rodent model, exposure to cisplatin at 5-10 mg/kg/day produced several neurological deficits, including hindlimb splaying, decreased forelimb and hindlimb grip strength, ataxia and skeletal muscle weakness. .Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay Additionally, exposure to chemotherapeutic agents has caused central-peripheral neuropathy in humans and laboratory animals, including rats and monkeys. Treatment with memantine significantly improved neurological deficits; this result was in agreement with [14] who reported that memantine significantly alleviated cisplatin-induced peripheral neuropathy in rats, which is evident by improvement in body weight, decrease in thermal hyperalgesia, improvement in motor coordination, increased grip strength, improved nerve conduction velocity and higher antioxidant enzymatic activities compared to rats treated with cisplatin[23]. Body weight is often the most sensitive indicator of the adverse effects of toxic substances. The study revealed a decrease in body weight following cisplatin administration, which may be attributed to the direct effect of cisplatin on growth, excessive degradation of tissue proteins, or decreases in both plasma and tissue proteins. Evidence has been accumulating that lack of protection against reactive oxygen species (ROS) and lack of repair of oxidative DNA damage play a significant role in the progression of neurodegenerative diseases. Extensive research has linked neurodegenerative diseases to an overactive glutamatergic system, which causes overactivation of NMDA receptors, excessive Ca2+ influx, and eventual cell death. Memantine is a neuroprotective agent capable of inhibiting the pathological characteristics of NMDA receptor activation and, at the same time, allows the necessary physiological and cognitive functions to remain intact. This drug has been shown to normalize disorders of synaptic plasticity and cognition that typically follow excitotoxic neuronal damage. Neuroprotective drugs such as memantine with clinical application in neurological diseases could reduce genomic instability in brain tissue in addition to improving cognitive functions. Recent studies have shown that memantine decreases neuronal cell damage evoked by staurosporine and doxorubicin. To confirm thesestudies, memantine at a dose of 3 - 15 mg ⁄ kg decreased DNA damage in brain tissue. No stereotyped behavior or signs of toxicity were observed in this dose range, suggesting that decreased brain DNA damage may be associated with neuroprotective effects. effects of memantine The frequency of micronuclei increased, although without statistical significance, suggesting that memantine was not capable of inducing mutagenicity. In a study using lipopolysaccharide infusion to induce neuroinflammatory damage, memantine decreased the likelihood of microglial activation by preventing the release of arachidonic acid and proinflammatory factors from neurons. Memantine increased the mRNA levels of brain-derived neurotrophic factor, which may mediate its neuroprotective effects, reversed the loss of cell viability, and decreased caspase-3⁄7 activity and ROS level induced by catechol (a component of cigarette smoke). In the central nervous system, both in vivo and in vitro, previous studies have indicated that the increase in proinflammatory cytokines can be reduced by NMDAR antagonist. Memantine, a well-characterized NMDAR antagonist, is used to treat dementia and Parkinson's disease in the clinic, and also protects neurons from some models of neurological damage such as head trauma, ischemic stroke, spinal cord ischemia, or neuroinflammation. Therefore, in the process of neuroinflammation, glutamate release and NMDAR activation can increase neuroinflammation and further deteriorate the CNS injury. Excessive activation of NMDA receptors in the central nervous system induces Ca2+ overload and oxidative stress, leading to neurodegeneration. These observations have stimulated the development of several NMDA antagonists, many of which are effective in animal models of neurodegeneration. Memantine can cause almost complete inhibition of NMDA receptors. Memantine blocks the NMDA receptor pore, therefore, synaptic transmission through NMDA receptors is maintained in the presence of memantine. On the other hand, this study suggests the possible usefulness of a pharmacological strategy based on a drug already widely used in the clinical setting. The availability of drugs that can be used to block NMDA receptors, such as memantine, contrasts with the future promise of gene therapies or other unproven strategies that may be needed for other potential therapeutic targets[12, 34, 35]. Chronic abstinence (6 months) alcohol ingestion produced learning deficits in rats in the Morris water maze. Treatment with memantine initiated at the beginning of the withdrawal phase (bolus of 20 mg/kg followed by 1 mg/kg every 12 hours for 4 weeks) produced a complete reversal of these behavioral disturbances. Memantine (30 mg/kg/day; po) for 2–3 weeks significantly improved the acquisition of the water maze task in mice without affecting swimming speed. Memantine enhanced neurogenesis at therapeutically relevant concentrations in cortical cultures in vitro (best effects were observed at 1 µM, with 140% control neurogenesis) and in the subventricular zone of the DG and forebrain in vivo (7.5 mg/kg PO once daily for 14 days, approximately 126% of control neurogenesis), in another study, acute treatment of rats treated with memantine (20 mg/kg) also led to increased neurogenesis in 'hippocampus. Chronic dietary memantine (31 mg/kg/day) for 14 days prevented quinolinic acid-induced death, seizures, and hippocampal damage[12, 38]. Rats infused with quinolinic acid alone showed clear deficits.