Abstract
Memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist approved for treating Alzheimer’s disease, has a good safety profile and is increasingly being studied for possible use in a variety of non-dementia psychiatric disorders. There is an abundance of basic and clinical data that support the hypothesis that NMDA receptor hypofunction contributes to the pathophysiology of schizophrenia. However, there are numerous randomized, double-blind, placebo-controlled clinical trials showing that add-on treatment with memantine improves negative and cognitive symptoms, particularly the negative symptoms of schizophrenia, indicating that memantine as adjunctive therapy in schizophrenia helps to ameliorate negative symptoms and cognitive deficits. It remains unclear why memantine does not show undesirable central nervous system (CNS) side effects in humans unlike other NMDA receptor antagonists, such as phencyclidine and ketamine. However, the answer could lie in the fact that it would appear that memantine works as a low-affinity, fast off-rate, voltage-dependent, and uncompetitive antagonist with preferential inhibition of extrasynaptic receptors. It is reasonable to assume that the effects of memantine as adjunctive therapy on negative symptoms and cognitive deficits in schizophrenia may derive primarily, if not totally, from its NMDA receptor antagonist activity at NMDA receptors including extrasynaptic receptors in the CNS.
Highlights
The pathogenesis of schizophrenia remains unestablished to date
This review examines the past and current information on memantine as adjunctive therapy in schizophrenia and seeks to ascertain if the NMDA receptor antagonist activity of memantine could contribute to adjunctive therapy effects in schizophrenia
There is an abundance of data that support the hypothesis that NMDA receptor hypofunction contributes to the pathophysiology of schizophrenia
Summary
The pathogenesis of schizophrenia remains unestablished to date. according to the dopamine hyperactivity theory, hyperactivity of dopaminergic neurotransmission is assumed to play a central role. The residual symptoms, which do not respond completely to treatment with conventional antipsychotics (i.e., those having functional D2 receptor antagonist activity), are thought to derive from a non-dopaminergic mechanism. Pharmaceutical drugs with various mechanisms of action have been considered or tried as adjunctive therapy for schizophrenia patients. These drugs include serotonin-reuptake inhibitors, 5-HT2C, 5-HT3, and 5-HT6 receptor antagonists, α-7 nicotinic and M1 muscarinic receptor agonists, GABA-A receptor agonists, GABA-B receptor antagonists, anti-inflammatory drugs, cannabinoids, such as cannabidiol, cholecystokinin agonists, neurokinin-3 receptor antagonists, and glutamatergic agents [3]. Memantine is one of the adjunctive therapy options for treating schizophrenia patients It is an N-methyl-d-aspartate (NMDA) receptor antagonist that has been approved for the treatment of moderate to severe Alzheimer’s disease [4]. This review examines the past and current information on memantine as adjunctive therapy in schizophrenia and seeks to ascertain if the NMDA receptor antagonist activity of memantine could contribute to adjunctive therapy effects in schizophrenia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
