TY - JOUR
T1 - Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia
AU - Koola, Maju Mathew
AU - Buchanan, Robert W.
AU - Pillai, Anilkumar
AU - Aitchison, Katherine J.
AU - Weinberger, Daniel R.
AU - Aaronson, Scott T.
AU - Dickerson, Faith B.
N1 - Funding Information:
Maju Koola was supported by the NIMH funded 5R13MH064074 to present part of this manuscript at the 2010 APA Research Colloquium for Junior Investigators in New Orleans, LA, May 22–26. We like to thank Robert Schwarcz, PhD for Fig. 2 and Robert Freedman, MD for reviewing the manuscript.
Funding Information:
Faith Dickerson is funded by the Grant 07R-1690 from the Stanley Medical Research Institute .
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Cognitive impairments
KW - Galantamine
KW - Memantine
KW - Schizophrenia
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U2 - 10.1016/j.schres.2014.04.037
DO - 10.1016/j.schres.2014.04.037
M3 - Review article
C2 - 24878431
AN - SCOPUS:84904107880
SN - 0920-9964
VL - 157
SP - 84
EP - 89
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -