title: Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia.
abstract: The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and Treatment Units for Research on Neurocognition and Schizophrenia projects were designed to facilitate the development of new drugs for the treatment of cognitive impairments in people with schizophrenia. The MATRICS project identified three drug mechanisms of particular interest: dopaminergic, cholinergic, and glutamatergic. As a group, while people with schizophrenia have moderate cognitive impairment, it is the best predictor of long-term outcome. Unfortunately, there are no approved medications for cognitive impairment in this population. Hence, the development of new pharmacological approaches is critical for reducing illness-related disability. The combination of an acetylcholinesterase inhibitor (AChEI) and memantine is more effective than either medication alone to improve cognition in Alzheimer's dementia. Galantamine is not only an AChEI, but also a positive allosteric modulator of the α4β2 and α7 nicotinic receptors. Hypofunction of N-methyl-d-aspartate (NMDA) receptors has been implicated in the pathophysiology of cognitive symptoms in schizophrenia and hence memantine may positively impact cognition. Memantine decreases the tonic NMDA current and galantamine enhances the action potential mediated by a postsynaptic NMDA current. This results in an increased signal transmission; therefore, a greater signal-to-noise ratio occurs with the combination than memantine alone. Galantamine improves the α-amino-3-hydroxy-5-methyl-4-isoxazol-propionate (AMPA)-mediated signaling which could be neuroprotective and may improve memory coding. The combination of galantamine and memantine may be particularly effective in schizophrenia in order to increase the selective cognition enhancement produced by either medication alone. In the future, multitarget-directed ligands may play a role in the treatment of complex diseases like schizophrenia.
authors.affiliation: Sheppard Pratt Health System, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: majujuju@yahoo.com.
authors.forename: Maju Mathew
authors.initials: MM
authors.lastname: Koola
authors.affiliation: Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Buchanan
authors.affiliation: Department of Psychiatry and Health Behavior, Georgia Regents University, Augusta, GA, USA.
authors.forename: Anilkumar
authors.initials: A
authors.lastname: Pillai
authors.affiliation: Department of Psychiatry and Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
authors.affiliation: Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.affiliation: Sheppard Pratt Health System, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Aaronson
authors.affiliation: Sheppard Pratt Health System, Baltimore, MD, USA; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Faith B
authors.initials: FB
authors.lastname: Dickerson
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005702:Galantamine / Q000627:therapeutic use*; D006801:Humans; D008559:Memantine / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D018697:Nootropic Agents; D005702:Galantamine; D008559:Memantine
keywords: Cognitive impairments; Galantamine; Memantine; Schizophrenia