Galantamine-Memantine Combination as an Antioxidant Treatment for Schizophrenia

Abstract

Purpose of Review-The objective of this article is to highlight the potential role of the galantamine-memantine combination as a novel antioxidant treatment for schizophrenia.Recent Findings-In addition to the well-known mechanisms of action of galantamine and memantine, these medications also have antioxidant activity. Furthermore, an interplay exists between oxidative stress, inflammation (redox-inflammatory hypothesis), and kynurenine pathway metabolites. Also, there is an interaction between brain-derived neurotrophic factor and oxidative stress in schizophrenia. Oxidative stress may be associated with positive, cognitive, and negative symptoms and impairments in white matter integrity in schizophrenia. The antipsychoticgalantamine-memantine combination may provide a novel strategy in schizophrenia to treat positive, cognitive, and negative symptoms. Summary-A "single antioxidant" may be inadequate to counteract the complex cascade of oxidative stress. The galantamine-memantine combination as "double antioxidants" is promising. Hence, randomized controlled trials are warranted with the antipsychotic-galantamine-memantine combination with oxidative stress and antioxidant biomarkers in schizophrenia.

Antioxidant Activity of a Novel Acetylcholinesterase Inhibitor: In Vivo and Ex vivo Studies

“…GAL has an antioxidant activity related with the enolic OH group [6]. One of the mechanisms by which GAL improves the mental function in Alzheimer's dementia is thought to be its antioxidant effect [49][50][51]. CU also is a proven antioxidant and brain protector [52][53][54].…”

Alpha7 nicotinic‐N‐methyl‐D‐aspartate hypothesis in the treatment of schizophrenia and beyond

“…This integrative pharmacology approach (Collis, 2006; Geerts et al, 2020; Gribkoff & Kaczmarek, 2017; Koola, 2019a; Koola et al, 2014) may be applicable to other combination treatments targeting glutamatergic‐nicotinergic systems concurrently as shown in Table 2. The combination of glutamatergic‐nicotinergic medications may target the quintuple hypotheses (dopamine‐nicotinic/cholinergic‐glutamate/NMDA‐GABA‐kynurenic acid [KYNA], Koola, 2018a) and improve the antioxidant biomarkers (Koola et al, 2019) as shown in Figure 1. The combination treatment may improve positive, cognitive, and negative symptoms of schizophrenia (Koola, 2018a; Koola et al, 2019).…”

“…The combination of glutamatergic‐nicotinergic medications may target the quintuple hypotheses (dopamine‐nicotinic/cholinergic‐glutamate/NMDA‐GABA‐kynurenic acid [KYNA], Koola, 2018a) and improve the antioxidant biomarkers (Koola et al, 2019) as shown in Figure 1. The combination treatment may improve positive, cognitive, and negative symptoms of schizophrenia (Koola, 2018a; Koola et al, 2019). Finally, the combination also may stabilize other major pathophysaiological mechanisms (including the KYNA‐centric pathophysiology [Koola, 2020]) and biomarkers as shown in Figures 1–3.…”

“…There is burgeoning preclinical (Egea et al, 2007; Hodgkins & Schwarcz, 1998; Kety, 1959; Sobrado, Roda, López, Egea, & García, 2004) and clinical evidence on lactate as a biomarker in schizophrenia and beyond (Altschule, Henneman, Holliday, & Goncz, 1956; Regenold et al, 2009; Sullivan, et al, 2019). The galantamine‐memantine combination may decrease lactate concentration (Koola et al, 2019), which may improve cognition (Rowland et al, 2016). N ‐acetylaspartate, a measure of neuronal integrity, increased with galantamine (Iosifescu et al, 2009) and memantine (Fayed et al, 2019) treatment.…”

“…A synergy between nicotinic and NMDA receptors may be necessary to induce synaptic plasticity and BDNF‐dependent LTP (Massey et al, 2006). Galantamine and memantine may synergistically enhance BDNF (Koola et al, 2018; Koola et al, 2019). Among biomarkers of cognition in schizophrenia, BDNF has the majority of evidence (Penadés et al, 2015; Peng, Li, Lv, Zhang, & Zhan, 2018).…”