Memantine in neurological disorders – schizophrenia and depression

Abstract

Memantine is used in Alzheimer’s disease treatment as a non-competitive modern-affinity strong voltage-dependent N-methyl-D-aspartate receptor antagonist. The fundamental role of these receptors is to bind glutamate: the main excitatory neurotransmitter in the brain, believed to play a crucial role in neuronal plasticity and learning mechanisms. Glutamate transmission plays an important role in all internal CNS structures and maintains the physiological state of the brain. Excessive glutamate transmission can lead to enlarged calcium ion current which may cause neurotoxicity; however, insufficient transmission can drastically alter the information flow in neurons and the brain, potentially causing schizophrenia-like symptoms by replacing lost information with completely new stimuli. Hence, it is possible that the modulation of NMDA activity may give rise to pathophysiological states. Available literature and clinical trials indicate that memantine is well tolerated by patients, with very few and light side effects. There is a belief that memantine may also benefit other conditions such as schizophrenia and depression.

Memantine Modulates Oxidative Stress in the Rat Brain following Experimental Autoimmune Encephalomyelitis

“…Memantine is a weak, uncompetitive antagonist of the NMDA receptor that has been approved by the European Union and the U.S. Food and Drug Administration (FDA) for the treatment of dementia and Alzheimer’s disease. In contrast to other NMDAR channel blockers such as dizocilpine, ketamine, and phencyclidine, which also inhibit NMDA receptors in a noncompetitive manner, memantine does not exhibit serious side effects [ 31 ]. Due to its uncompetitive antagonism and relatively fast off-rate, memantine blocks excessive NMDAR activation but allows for low (physiological) levels of NMDAR activity seen during normal neurotransmission.…”

Can Ketogenic Diet Improve Alzheimer's Disease? Association With Anxiety, Depression, and Glutamate System

“…In this regard, the efficacy of different antioxidants that prevent and reverse AD when combined with adequate diets has been seen (78), highlighting vitamin C (79), α-lipoic acid (80) or the polyphenols epigallocatechin gallate and resveratrol (which can also prevent the neurotoxic effects of β-amyloid protein) (81), while drugs such as donepezil, galantamine and rivastigmine, which act as inhibitors of acetylcholinesterase derived from the accumulation of β-amyloid, could be more effective in advanced stages of the disease (82). Finally, and directly related to anxiety and depression variables, main focus of our study, the combination with glutamate inhibitors such as memantine or lamotrigine could improve the effectiveness of the impact of this diet on these variables, by completing the mechanisms related to the neurotransmitter already analyzed (83)(84)(85)(86).…”

Systemic Response to Infection Induces Long-Term Cognitive Decline: Neuroinflammation and Oxidative Stress as Therapeutical Targets

“…Clinical trials with levetiracetam, an antiepileptic drug, were carried out in Alzheimer's and septic patients with promising results showing inhibition of neuronal dysfunction and inflammatory parameters (Erbaş et al, 2013;Vossel et al, 2021). Memantine, an NMDA antagonist already used to treat Alzheimer patients due to its activity reducing excitotoxic neuronal death (Czarnecka et al, 2021), could also be a candidate to act as an additive therapeutical drug to prevent cognitive sequel associated with infectious diseases. Of course, the safety profile of such drugs must be taken into consideration, especially their combined use with standard therapy in critically ill.…”